Growth Of Nb Research Articles

Selective growth of Nb–Fe–B intermetallic compounds for the direct separation of rare earths based on manipulating liquation

Since the primary goal of industrialization has changed to carbon neutrality, the importance of rare earths (REs) has increased due to their criticality in green industries. The attainment of sustainable resources via green production processes is necessary due to the increasing need for REs. Liquid metal extraction is regarded as a leading technology for supporting the sustainability of resources based on the selective reactivity between REs and extractants. However, this process requires multiple stages, including pretreatment, extraction and separation, which are considered bottlenecks in industrialization. In this work, reverse selectivity is applied instead of conventional liquid metal extraction (c-LME) for the direct separation of REs in a single stage. Niobium (Nb) is selected because of its thermodynamic properties for enhancing the selectivity of the reactions between the extractant and other elements, excluding REs. The process is thermodynamically designed for liquation systems, and it reflects the interactions between the extractant and magnets. The solidification behavior based on the selective growth of phases without REs is shown with variations in the composition and cooling rate to confirm the kinetics. The composition prevents the formation of RE-Fe intermetallic compounds, and excess Nb is considered a bottleneck for separating REs. In addition, the cooling rate influences the agglomeration of RE as a layer. Because of the manipulation of the liquation, 92.89% of the REs are successfully separated in the form of accumulated layers. This effective process for the direct separation of REs is verified through thermodynamic and experimental assessments. Overall, this investigation can provide new guidelines for the construction of a circular economy after improving the energy efficiency of this system in future research.

Chemical growth of Niobium-doped vanadium pentoxide on aminated graphene for all-solid-state asymmetric supercapacitors

In this investigation, niobium-doped vanadium pentoxide (Nb–V2O5) was grown on the surface of amine-functionalized graphene nanosheets (NH2-Gr) using an in-situ hydrothermal method and explored the hybrid material as a positive electrode for the fabrication of an all-solid-state asymmetric supercapacitor (ASC). We have used KOH-loaded poly(acrylonitrile-co-1-vinylimidazole) (KOH/P(AN-Co-VIM)) gel as a solid electrolyte-cum-separator and exfoliated graphene (XGnP) as a negative electrode in the ASC. The morphological analysis of the Nb–V2O5/NH2-Gr hybrid revealed homogeneous growth of Nb–V2O5 on NH2-Gr nanosheets, while surface analysis confirmed a large fraction of mesopores with large surface areas in the hybrid. The hybrid electrode achieved a high specific capacitance of 1141.1 F/g at 1 A/g with 80.3% capacitance retention even after a 10-fold increase in current density, a significantly higher performance than a pure Nb–V2O5 electrode. As-assembled solid-state ASC device delivered a high energy density of 79.39 Wh kg−1 at a power density of 280.3 W kg−1, even though it retained high energy density at a higher power density of 12 kW kg−1. The ASC exhibited slow a self-discharge rate owing to the suppression of Ohmic leakage by the use of KOH/P(AN-co-VIM) gel electrolyte. Thus, the as-synthesized Nb–V2O5/NH2-Gr hybrid is an ideal alternative candidate for future supercapacitors.

AlN and Nb(C,N) Composite Precipitation Behaviors and Their Effects on Austenite Grain Growth in SCr420H High‐Temperature Carburized Gear Steel

The effects of nitrogen (N) and niobium (Nb) contents on the precipitation behaviors of AlN, Nb(C,N), and AlN‐Nb(C,N) precipitates and austenite grain growth during the pseudo‐carburizing process are investigated for the carburized steel SCr420H. The results indicate that an increase of N content from 0.011% to 0.019% leads to the emergence of fine and uniform austenite grain structure in the sample while being held at 930 °C for 6 h, which is attributed to a notable rise in the number density of AlN and a decrease in the coarsening rate of AlN. In the steel containing 0.023% Nb, the composite precipitates AlN‐Nb(C,N) play a primary role in the pinning effect on austenite grains growth. The isolated Nb(C,N) and AlN precipitates have minor pinning effects due to their very low volume fractions. Nb(C,N) cap forming on AlN substrate obeys the Shoji–Nishiyama orientation relationship. The favorable lattice matching between AlN and Nb(C,N) and accelerated coarsening rate of Nb(C,N) cap decrease hindrances to the nucleation, growth, and coarsening of Nb(C,N) on AlN substrate. Meanwhile, these simultaneous effects also suppress the same processes for the isolated Nb(C,N) in the matrix.

Tuning Epitaxial Growth of Nb on MgO(100)

AbstractNiobium thin films are central to many applications, such as superconducting radio‐frequency cavities and superconducting qubits, due to its relatively high superconducting temperature and easiness to form heterostructures. However, literature on epitaxial growth of Nb on one of the most commonly used substrates, that is MgO, reports contradicting results. In the present parametric study, a coherent picture of how the crystalline orientation and the film morphology depend on the growth parameters is presented. The effects of growth parameters such as growth temperature, growth rate, deposition technique, and surface quality on the transport properties of the superconductor are discussed. In light of the new findings, an overview on previously published results and proposed nucleation and growth mechanisms is also given.

Performance of newly introduced fodder crops in ricewheat cropping system in adopted villages of Bareilly district in North Western U.P.

Two demonstrations were conducted in the adopted villages of IVRI for transfer of technology from lab to land programme.Trials were conducted in the project villages viz., Mohanpur, Kalapur in 2003-4 and khata, Bhansar during 2013-14 after ten years. Napier Hybrid NB 21, multi cut Bajra (Ganga kaveri,Pearl millet) as new crops were introduced in the study area .Forage maize (Sweta) was grown for comparative study as a control forage crop. The growth of napier Hybrid NB 21 was found to be fast growing crop over the other forage crop during summer and rainy seasons.Napier Hybrid raised wih scientific package of practices on farmers field.This crop gave 825.1 q/ha green fodder.the crop was harvested 4-5 times by the farmers.Maize cultivar Sweta was harvested at 45-75 days after sowing.This maize provided for one month fodder while, NB hybrid gave green fodder round the year. Maize gave 525.4 q/ha green fodder. Forage liking of animal feeding or palatability was maximum for forage maize. Pealmillet multi cut cultivar Ganga Kaveri harvested 3-4 times by September and produced 445.7 q/ha leafy, succulent fodder to milch animals during summer and rainy seasons. This was the second choice of animals. This was found to be good for feeding dairy animals long with wheat straw in 50:50 ratio of green and dry feeding balanced diet. However, palatability of NBH was after Multi Cut Bajra. After ten years area under forage crops was inceased 2-3 times. NBH from zero to 20 ha and MCB 3 ha and maize from 2 ha to 7 ha in the adopted villages. Some farmers started green fodder for sale in Rithoura to get more profits per acer of land. Technology adoption rate was higher in adopted villages than the near bynon adopted villages.

Influence of microstructural features on the growth of nanotubular oxide layers on β-phase Ti-24Nb-4Zr-8Sn and α + β-phase Ti-13Nb-13Zr alloys

Anodization of titanium alloys allows us to obtain nanotube oxide structures consisting of a mixture of oxides of alloying additives which might extend their scope of application and improve their surface properties. However, the complex microstructure of two-phase α + β Ti alloys presents a much greater influence on the homogeneity of nanotubular layers as compared to a single α-phase pure titanium. In this work, we analyzed how changes at the microstructural level (the amount, size or shape of the precipitates of individual phases) affect the growth of nanotubes on two biomedical alloys Ti-24Nb-4Zr-8Sn and Ti-13Nb-13Zr after different heat treatment. We found that morphology of nanotubular oxide layer imitate the microstructure of the substrate quite accurately what has been clearly seen especially for Ti-13Nb-13Zr alloy with a different size and morphology of α/α’ phase precipitates. The height of nanotubes was highly dependent on the β phase content, i.e. the higher the amount of the β phase, the higher the oxide nanotubes what is presumably due to the preferential growth of Nb 2 O 5 and ZrO 2 oxides. Moreover, the results showed that it is possible to fabricate crystalline nanotubes on the annealed Ti-13Nb-13Zr substrates immediately after the anodization process without a typical post-heat treatment. We suppose that this results from the presence of crystalline transition layer after initial heat treatment as well as internal stresses in the two-phase microstructure that induced the crystalline transformation. • NTs layers were fabricated on α + β-phase Ti alloys with various microstructure. • Morphology of layers imitated the size and shape of α/α’ phase precipitates. • The height of NTs grew with the higher amount of β phase. • Crystalline NTs were obtained on Ti-13Nb-13Zr without typical post-heat treatment.

Preparation of flexible thin films from epitaxially grown anatase Nb: TiO2 using water‐soluble Sr3Al2O6 sacrificial layer

AbstractWith the aim of developing new electronic functionalities for flexible devices, a transfer process for the preparation of flexible conductive thin films was examined using epitaxially grown anatase Nb: TiO2. Using pulsed laser deposition (PLD), water‐soluble Sr3Al2O6 (SAO) was deposited on a single‐crystalline LaAlO3 (100) substrate (LAO) as a sacrificial layer, followed by the epitaxial growth of anatase Nb: TiO2 on the sacrificial layer. The Nb: TiO2/SAO/LAO multilayer sample bonded onto a flexible polymer sheet via an adhesive tape was soaked into distilled water to transfer the epitaxially grown Nb: TiO2 thin film from SAO/LAO to the polymer sheet. The transferred anatase Nb: TiO2 thin film retained the clear X‐ray diffraction peaks. Moreover, the areal transfer ratio was almost 100%, without the generation of significant impurity phases during the transfer process. On the basis of these results, the examined process was found promising for the preparation of flexible anatase Nb: TiO2 thin films. The voltage drop–current characteristics were measured successfully at room temperature for the transferred anatase Nb: TiO2 thin film using the standard four‐probe method with gold electrodes.

High cycle fatigue performance, crack growth and failure mechanisms of an ultrafine-grained Nb+Ti stabilized, low-C microalloyed steel processed by multiphase controlled rolling and forging

An effort has been made to examine the high cycle fatigue (HCF) properties including crack propagation characteristics and related fracture mechanisms of submicron-grained (SG) Nb + Ti stabilized low C steel processed through advanced multiphase-controlled rolling (MCR) and multiaxial forging (MAF). The HCF and other mechanical properties have been correlated with microstructural features characterized by light optical (LOM), transmission electron (TEM) and scanning electron microscopy (SEM), aided with electron backscatter diffraction (EBSD). TEM analysis near the fracture zones of the fatigue tested samples and corresponding fractographic analysis corroborated well in explaining the improved fatigue life of the SG steel. The fatigue strength was found to have a linear relationship with the tensile strength in both types of processed samples. The fatigue strength of the forged specimens was estimated to be nearly twice than that of the untreated annealed steel, demonstrating significantly different fracture characteristics. Intergranular fracture is found to be dominant in the rolled/forged specimens, in comparison to the transgranular fracture observed in the as-received steel. Such variances in fatigue strength and fracture characteristics have been endorsed to their microstructural constituents. Superior combinations of yield strength (YS), tensile strength (UTS), elongation (% El.) and high cycle fatigue strength (σf) (YS = 1027 MPa, %El. = 8.3%, σf = 355 MPa) were obtained in multiphase-controlled 15-cycle multiaxially forged (MAFed) specimens (processed in intercritical α+γ phase regime). An enhancement of the fatigue strength can be ascribed to the formation of evenly dispersed nano-sized fragmented cementite (Fe3C) particles (~35 nm size) present in the SG ferritic matrix (average ~280 nm size). The fine dislocation substructures/cells together with the nano-sized Fe3C particles could efficiently block the initiation and propagation of cracks thereby enhancing the fatigue endurance limit of the steel. Superior mechanical properties together with high fatigue resistance in the SG material render the present steels highly beneficial for high-strength structural applications.

Growth and mechanical properties of Nb[sbnd]Cr carbide coatings on graphite by TRD technique

Niobium‑chromium (NbCr) carbide coatings were deposited on graphite using the thermo-reactive deposition and diffusion (TRD) technique. The microstructure, hardness, and coefficient of thermal expansion were characterized to search for the optimal treatment parameters for hard and adherent coatings on graphite. The growth rate increased with treatment temperature for fixed treatment duration and remained constant at a constant temperature for about 6 h. The coatings were found to consist of alternating Nb and Cr layers, and this interesting multilayer structure might be explained by the thermodynamics of oxide reduction and carbide formation reactions. Compared to the single-carbides layer, the hardness of the complex coatings increased from about 2500 HV to above 3000 HV, and displayed a smaller gradient of the depth-dependent hardness from the coating to the substrate. The variation of coefficient of thermal expansion of the samples with temperature was similar to that of the graphite substrate at temperatures from 40 to 450 °C. These results showed the effectiveness of the TRD method for synthesizing hard and adherent carbide coatings on graphite, and for other coating/substrate systems with sharply dissimilar mechanical properties.

Targeting of Survivin Inhibits Neuroblastoma Cell Proliferation

Introduction High-riskneuroblastoma (NB) is an aggressive pediatric tumor which develops from the extracranial sympathetic nervous system and accounts for almost 15% of all childhood cancer-related deaths. Despite recent advancements in therapeutic approaches, the overall long-term survival rate for NB patients is still less than 50%. Drug- resistance, metastasis, tumor relapse, and drug-related toxicities mandate the development of less toxic and more effective novel therapeutic approaches for treating NB patients. Survivin is known to be involved in controlling cell division and apoptosis and belongs to the inhibitor of apoptosis protein family. Oncogenic activation of survivin has been reported in different cancers, including NB. We hypothesized that inhibiting surviving protein by using a specific small molecule inhibitor will inhibit NB cell proliferation, induce apoptosis, and sensitize tumor cells to chemotherapies. Methods NB patient datasets were analyzed using publicly available R2 Genomic analysis and visualization platform. Different NB cell lines, either MYCN-amplified NGP, IMR-32, LAN-5 or, MYCN non-amplified SH-SY5Y, SK-N-AS, CHLA-255 were used in the present study. Cell-Titer AQueous One Solution was used to perform cell proliferation assays as per the manufacturer's instructions. Clonogenic assays were performed using crystal violet dye. Apoptosis and cell cycle assays were performed using eBioscience Annexin V Apoptosis Detection Kit and Click-iT EdU Alexa Fluor 488 Flow Cytometry Assay Kit respectively, using Attune NxT Flow Cytometer. In vitro tumorigenic studies were performed by using Corning 3D spheroid microplate system. All the assays were performed at least three times with replicates. Results In the present study, we analyzed genomic datasets of 1135 NB patients and found that high expression of survivin coding gene BIRC5 strongly correlates with poor overall and event-free survival of NB patients. More aggressive tumors have significantly higher BIRC5 levels. To understand the effects of inhibiting survivin on NB growth, we used a specific small molecule inhibitor and performed cell proliferation and clonogenic assays. Results revealed that inhibition of survivin significantly inhibit NB proliferation and colony formation in all cell lines tested. Furthermore, survivin inhibition significantly induce apoptosis in NB cells and block the cell cycle progression. In vitro 3D spheroidal assays that recapitulate the in vivo tumor growth showed the survivin inhibitor significantly inhibits spheroid growth and induce apoptosis in a dose dependent manner. Conclusion Overall, our results suggest that survivin promotes the oncogenic potential of NB. Inhibition of survivin by using specific small molecule inhibitor is a novel therapeutic approach for NB. In our future efforts, we will combine the survivin inhibitor with chemotherapy drugs such as doxorubicin to develop a dual therapeutic approach for NB.

Structural properties of carbon composites doped with boron

The article considers morphology, chemical and phase composition of composite boro-carbon coatings, received by ion-plasma synthesis, depending on the boron content. Specimens of carbon coating doped with boron were obtained in vacuum unit by combined method coupled with co-deposition of carbon layer from pulse carbon plasma and its doping with boron atom flow. The obtained specimens of composite CC had embedded boron atoms with various concentration (NB), namely, 2.3 at.% were contained in ɑ-С91.2:B2.3, in ɑ-С79.3:B17.4 — 17.4 at.%, in ɑ-С53.3:B43.2 — 43.2 at.%. Carbon structures and carbon clusters graphitizationwere examined by X-ray photoelectron spectroscopy and Raman spectroscopy. Aiming at chemical interaction between carbon and boron in CC establishment we conducted mathematical processing of XPS for energy states C1s, B1s, O1s of carbon, boron and oxygen atoms. XPS C1s was presented as peaks superposition with centers located at 284.5; 285.5; 283.5 and 288 eV and consequently responsible for Csp2, Csp3, C–B and C–О carbon atom interaction. With the growth of NB in boron-doped carbon coating a grain structure is formed, its size and grain orientation regarding the surface of the substrate increase, resulting in a decrease in the coating layer surface roughness.

Suppression of nano-hydride growth on Nb(100) due to nitrogen doping.

Niobium superconducting radio frequency (SRF) cavities enable the operation of modern superconducting accelerator facilities. These cavities do not approach the theoretical performance limits of Nb due to the deleterious effects of surface defects and chemical inhomogeneities such as Nb hydrides. Nitrogen doping is known to consistently increase the cavity performance and inhibit Nb hydride growth, but a comprehensive understanding of Nb hydride growth and suppression is not yet realized. Scanning tunneling microscopy (STM), scanning tunneling spectroscopy (STS), and density functional theory (DFT) calculations presented herein elucidate the real-time, nanoscale structural and electronic evolution of undoped, hydrogen doped, and hydrogen and nitrogen doped Nb(100) due to the growth and suppression of Nb nano-hydrides. DFT calculations in agreement with the experimental data found unique near-surface phases stabilized upon dopant incorporation. The experimental STM and STS results and DFT calculations reported herein provide the first in situ and real-time nanoscale visualization and characterization of the effects of nitrogen doping on Nb hydride suppression and growth. Such information allows for further optimization of nitrogen doping procedures and advances in the performance of SRF materials for next-generation SRF-based accelerators and free electron lasers.

Bone Maturation as a Predictive Factor of Catch-Up Growth During the First Year of Life in Born Small for Gestational Age Infants: A Prospective Study.

Background: About 85–90% of children born small for gestational age (SGA) experience a catch-up growth that occurs mostly during the first year of life and results in a full stature recovery by the age of 2.Objective: To investigate the relation between bone maturation (BM) and catch-up growth during the first year of life in SGA infants.Method: Newborns whose weight and/or length was <-2 SD for gestational age were classified as SGA (group A). The study included a group of 32 SGA, 21 of which are full term [37–41 gestation weeks (GW), subgroup A1] and 11 preterm (30–36 GW, subgroup A2). Control group (B) consisted of 19 full-term and adequate-for-gestational-age (AGA) newborns. All the participants were born in the same hospital and period (January–December 2017). Chromosomal disorders, congenital defects, and maternal chronic diseases were criteria of exclusion. The study population underwent longitudinal evaluation of growth parameters and BM at 0, 3, 6, and 12 months. Assessment of BM was performed by an ultrasonographic (US) study of Béclard's nucleus (NB) (<3 mm at birth, meaning intrauterine delay of BM).Results: Significantly higher height velocity (HV) was observed in subgroup A2 vs. A1 (32.4 ± 8.0 vs. 25.6 ± 2.9 cm, p = 0.01); nevertheless, more subjects in subgroup A2 had height <-2 SD at year 1 than had subgroup A1 (27.3 vs. 0%, p = 0.01). Intrauterine delay of BM was more common in group A vs. B (59.4 vs. 21.2%, p = 0.0078) and in subgroup A2 vs. A1 (90.9 vs. 42.9%, p = 0.0086). In group A, HV over the first year of life negatively correlates with NB diameter assessed at birth (r = −0.6, p < 0.001) but positively correlates with NB growth (r = 0.52, p < 0.01). Moreover, SGA babies with intrauterine delay of BM showed higher HV and better height gain at 12 months' evaluation than did SGA with adequate BM (29.75 ± 3.1 vs. 23.8 ± 2.7 cm, p = 0.003).Conclusion: Neonatal BM should be regarded as a predictive factor of SGA height gain during the first year of life. US evaluation of NB is a useful noninvasive technique to identify intrauterine delay of BM, which positively correlates with early postnatal catch-up growth of SGA infants.

Evolution of Nb oxide nanoprecipitates in Cu during reactive mechanical alloying

Abstract

In situ growth of Fe and Nb co-doped β-Ni(OH)2 nanosheet arrays on nickel foam for an efficient oxygen evolution reaction

Fe, Nb co-doped β-Ni(OH)2 electrode exhibited excellent OER performance with an overpotential of 294 mV at 100 mA cm−2.

FUBP1 promotes neuroblastoma proliferation via enhancing glycolysis-a new possible marker of malignancy for neuroblastoma

BackgroundNeuroblastoma (NB) is one of the deadliest paediatric solid tumours due to its rapid proliferative characteristics. Amplified copies of MYCN are considered the most important marker for the prediction of tumour relapse and progression in NB, but they were only detected in 20–30% of NB patients, indicating there might be other oncogenes in the development of NB. The far upstream element binding protein 1 (FUBP1) was first identified as a transcriptional regulator of the proto-oncogene MYC. However, the expression and role of FUBP1 in NB have not been documented.MethodsFUBP1 expression was analysed from GEO database and verified by immunohistochemistry (IHC) and western blotting (WB) in NB tissues and cell lines. Cell proliferation and apoptosis were detected by Cell Counting Kit-8, Colony formation assay, EDU, TUNEL staining and flow cytometric analysis. Several glycolytic metabolites production was confirmed by ELISA and oxygen consuming rate (OCR). Luciferase assay, WB, chromatin immunoprecipitation (CHIP) were used to explore the mechanisms of the effect of FUBP1 on NB.ResultsFUBP1 mRNA levels were increased along with the increase in International Neuroblastoma Staging System (INSS) stages. High expression of FUBP1 with low N-Myc expression accounted for 44.6% of NB patient samples (n = 65). In addition, FUBP1 protein levels were remarkably increased with NB malignancy in the NB tissue microarray (NB: n = 65; ganglioneuroblastoma: n = 31; ganglioneuroma: n = 27). Furthermore, FUBP1 expression was negatively correlated with patient survival rate but positively correlated with ki67 content. In vitro experiments showed that FUBP1 promotes NB cell proliferation and inhibits cell apoptosis via enhancing glycolysis and ATP production. Mechanistically, FUBP1 inhibited the degradation of HIF1α via downregulation of Von Hippel-Lindau (VHL), the E3 ligase for HIF1α, resulting in upregulation of lactate dehydrogenase isoform B (LDHB) expression to enhance glycolysis. Overexpressed or silenced N-Myc could not regulate FUBP1 or LDHB levels.ConclusionsTaken together, our findings demonstrate for the first time that elevated FUBP1 promotes NB glycolysis and growth by targeting HIF1α rather than N-Myc, suggesting that FUBP1 is a novel and powerful oncogene in the development of NB independent of N-Myc and may have potential in the diagnosis and treatment of NB.

Abstract 2890: Paternal pre-conception stress as a potential risk factor for neuroblastoma

Abstract Neuroblastomas (NBs) are pediatric tumors that lack adequate treatment for their aggressive form, despite many efforts focusing on novel therapies. Although the disease is known to have a genetic background, its etiology cannot be explained solely by genetics. Yet, the role of environment in NB development is understudied. Thus, there are no established risk factors for NB aside from rare genetic predispositions and therefore no preventative measures. NBs arise due to defects in sympathetic neuron (SN) differentiation, which occurs in the fetus. Thus, we hypothesize that prenatal or pre-conception exposures may interfere with this process and promote NB. Maternal stress during pregnancy and paternal pre-conception stress induce neurodevelopmental defects in offspring by direct effects on fetal development or epigenetic changes, respectively. Indeed, we have previously shown that in a mouse model of NB prenatal stress interferes with SN differentiation in offspring, accelerating NB development and leading to its increased frequency and malignancy. The goal of the current study was to determine if a similar increase in risk of NB development can result from paternal pre-conception stress. To test the effect of paternal stress on NB, we subjected TH-MYCN males to 6 weeks of chronic unpredictable stress (CUS) prior to mating with wild type females and assessed the impact of stress on 1) miRNA content in the germline (RNAseq); 2) fertility and fetal survival; 3) NB frequency, latency, growth and metastasis in their hemizygous TH-MYCN offspring (periodic MRI, histological analyses). CUS resulted in significant changes in non-coding RNA content of the germline, including miRNAs and tsRNAs. Of particular interest was a stress-induced down-regulation of sperm miRNAs, including miR-200b and miR-128, which are involved in neuroblast differentiation, inhibit NB invasiveness and are inactivated in NB tumors. Paternal stress decreased the rate of successful pregnancies from 75% in controls to 37.5% and increased frequency of death in utero from 5.5% to 29.2% (p=0.02). Moreover, offspring of stressed fathers exhibited accelerated NB development (60% vs 0% of mice with tumors at 6 weeks of age for CUS and control groups, respectively; p=0.03) and growth (p=0.3), higher tumor frequency (60% vs 25% at 14 weeks of age, p=0.03), as well as a trend toward a more metastatic phenotype. However, these effects on NB formation and phenotype were observed solely in male offspring. In summary, our data provide the first evidence for the role of paternal preconception stress in NB development. If confirmed, our findings may open new avenues for NB prevention and identifying biomarkers of increased NB risk. Citation Format: Sung-Hyeok Hong, Susana Galli, Raquel Santana da Cruz, Lu Jin, Larissa Wetlisbach, Shiya Zhu, Abir Malik, Jason Tilan, Sonia de Assis, Joanna B. Kitlinska. Paternal pre-conception stress as a potential risk factor for neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2890.

Abstract 4570: Selective depletion of regulatory T cells suppressed neuroblastoma tumor growth in mice

Abstract Purpose of the study Neuroblastoma (NB) is the most common solid extracranial tumor in childhood. Regulatory T cells (Treg) are known to have immune suppressive capacity and to be involved in tolerance establishment. As they support tumor growth and help some tumors to overcome recognition by the host, they are considered to be an important target. Treg are reportedly increased in blood of NB patients. However, there are no scientific proofs to date that they are involved in neuroblastoma growth. To address this important question we employed Foxp3-DTR mice to selectively deplete Treg upon orthotopic application of syngeneic neuroblastoma cells. Methods Orthotopic NB tumors were generated in mice Foxp3-DTR mice and in C57Bl/6J controls by subcapsular tumor cell injection of NB975A cells into the left kidney. Primary tumor growth was analysed for 23 days by high frequency ultrasound measurement. To deplete Treg, InjectionDepletion of Diphtheria Toxin (DT, 15 ng/g bodyweight) intraperitoneally every 4 days in Foxp3.DTR mice depleted the Treg pool. Control Foxp3.DTR animals received PBS and control C57B/l6 received DT. All mice were sacrificed 23 days after tumor inoculation. Tumor as wells as immune cells harvested from spleen and inguinal lymph nodes were analyzed by Flow Cytometry, Immunofluorescenceimmunohistochemistry and qRT-PCR. Results In control mice bearing tumors, Treg presence was confirmed at the contact zone between the kidney and the growing, inoculated tumor. Mice devoid of Treg (Foxp3-DTR+DT) showed a significantly reduced tumor growth compared to animals with normal Treg frequencies (Foxp3-DTR+PBS). Tumor growth in wild type controls was not affected by the application of DTR. Conclusion Ablation of Treg hindered the growth of NB, strongly suggesting their potential as therapeutic target for this aggressive childhood tumor. Citation Format: Sophie von Lenthe, Christine Weißenborn, Ana Claudia Zenclussen, Stefan Fest, Leonid Metelitsa. Selective depletion of regulatory T cells suppressed neuroblastoma tumor growth in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4570.

The TNFR1/mTNFα signaling axis initiates tumor-promoting inflammation and is associated with poor outcome in neuroblastoma

Abstract Neuroblastoma (NB) is a poorly differentiated, aggressive pediatric solid tumor for which half of high-risk cases have no identified genetic alteration. While such high-risk tumors are often infiltrated by macrophages that generate an inflammatory gene signature predictive of poor outcome, the initiation mechanism of this pro-tumorigenic inflammation remains unknown. In our analysis of clinical outcome-linked NB gene expression data, high tumor expression of TNFR1 was strongly correlated with poor event-free survival (5-year EFS 15% vs 70%, bonf p=9.3e-07), highlighting the potential importance of TNFα signaling in NB. Using TNFα knockout human NB cell lines, we determined that monocytes, but not NB cells, produce TNFα during in vitro co-culture. Furthermore, using a TNFα converting enzyme inhibitor to prevent secretion of soluble TNFα, we found that the membrane-bound form of TNFα (mTNFα) expressed on monocytes was critical for NF-κB pathway activation and downstream production of IL-6, a known NB growth factor. Neutralization of TNFα or its receptor TNFR1, but not TNFR2, in a monocyte-NB co-culture prevented NF-κB activation in monocytes, reducing IL-6 production by 50% compared to controls (p &amp;lt;0.01). Our results demonstrate that TNFR1-expressing NB cells activate monocytes via contact-dependent mTNFα signaling, leading to NF-κB activation and production of IL-6, a known driver of NB progression and therapy resistance. These findings reveal a novel, druggable mechanism of tumor-promoting inflammation in NB.

Effects of Carbon Variation on Microstructure Evolution in Weld Heat-Affected Zone of Nb-Ti Microalloyed Steels

We investigated the effects of C concentration variation from 0.028 to 0.058 wt pct on microstructure of the coarse grained heat-affected zone (CGHAZ) of low heat input girth welded Ti-Nb microalloyed steels by using electron microscope and atom probe tomography. It is found that the CGHAZ microstructure exhibits a systematic response to C variation. Increased C raises the temperature for precipitation of NbC. This leads to coarser (Ti, Nb)N-Nb(C, N) but finer delayed strain-induced NbC in the high-C steel than in the low-C steel. Fine strain-induced NbC are ineffective in preventing austenite grain coarsening in CGHAZ due to their fast dissolution upon heating. For a given inter-particle spacing originally determined by (Ti, Nb)N particles, increased epitaxial growth of Nb(C, N) on pre-existing (Ti, Nb)N in the high-C steel results in a smaller austenite grain size of 34 µm in the CGHAZ of the high-C steel than that of 52 µm in the low-C steel. Increased C promotes a microstructure consisting of bainitic lath structure with C Cottrell atmospheres at dislocation debris and martensitic layers of 30 to 100 nm in thickness at inter-lath boundaries in the CGHAZ. Increased C promotes configuration of crystallographic variants belonging to different Bain groups in the neighbors, preferentially twin-related variant pairs within a bainite packet.