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• Mass transfer across a gas–liquid interface of acoustic cavitation is investigated. • Time-averaged Sherwood number is decreased with sound pressure amplitude. • Time-averaged Sherwood number can be negative value due to area and shell effect. • The instantaneous Sherwood number is varied in the range of O (101) ∼ O (102). In the present study, mass transfer across a gas–liquid interface of acoustic cavitation bubble is numerically investigated. The volume of fluid (VOF) method coupled with a continuous species transfer model is used to simulate the bubble dynamic behavior and mass transfer across the gas–liquid interface. Chemical species are transferred repeatedly between the liquid and gas phases in accordance with the bubble oscillation, and the chemical species are transferred into the bubble during an expansion phase, and to the outside of bubble during a compression phase. Time-averaged Sherwood number is decreased with an amplitude of sound pressure due to area effect and shell effect , and its value becomes negative at high pressure amplitude. Meanwhile, the instantaneous Sherwood number is largely varied in accordance with the bubble oscillation, and its magnitude becomes O (101) ∼ O (102). [ABSTRACT FROM AUTHOR]

Recent regenerative studies using human pluripotent stem cells (hPSCs) have developed multiple kidney-lineage cells and organoids. However, to further form functional segments of the kidney, interactions of epithelial and interstitial cells are required. Here we describe a selective differentiation of renal interstitial progenitor-like cells (IPLCs) from human induced pluripotent stem cells (hiPSCs) by modifying our previous induction method for nephron progenitor cells (NPCs) and analyzing mouse embryonic interstitial progenitor cell (IPC) development. Our IPLCs combined with hiPSC-derived NPCs and nephric duct cells form nephrogenic niche- and mesangium-like structures in vitro. Furthermore, we successfully induce hiPSC-derived IPLCs to differentiate into mesangial and erythropoietin-producing cell lineages in vitro by screening differentiation-inducing factors and confirm that p38 MAPK, hypoxia, and VEGF signaling pathways are involved in the differentiation of mesangial-lineage cells. These findings indicate that our IPC-lineage induction method contributes to kidney regeneration and developmental research. [Display omitted] • A selective induction method for renal IPC-like cells from hiPSCs was established • Co-culture of hiPSC-derived IPLCs and NPCs form mesangium-like structures in vitro • hiPSC-derived IPLCs develop mesangial and EPO-producing cell lineages in vitro • Crucial roles of p38 MAPK signaling in mesangial-lineage development were revealed Tsujimoto et al. establish the selective induction of renal interstitial progenitor-like cells (IPLCs) from hiPSCs. These IPLCs form mesangium-like structures when combined with hiPSC-derived nephron progenitor cells and selectively differentiate into mesangial and EPO-producing cells in vitro , revealing crucial roles of p38 MAPK, VEGF, and hedgehog signaling in interstitial development. [ABSTRACT FROM AUTHOR]

[Display omitted] • Largest reactor pressure vessel steel embrittlement database available includes test reactor and surveillance data. • Machine learning model for accurate prediction of embrittlement with low errors and large applicability domain. • Well-calibrated uncertainty estimates for informing uncertainty quantification on new predictions. • Use machine learning model to assess physical trends, construct embrittlement curves, and predict alloy life extension behavior. An essential aspect of extending safe operation of the world's active nuclear reactors is understanding and predicting the embrittlement that occurs in the steels that make up the Reactor pressure vessel (RPV). In this work we integrate state of the art machine learning methods using ensembles of neural networks with unprecedented data collection and integration to develop a new model for RPV steel embrittlement. The new model has multiple improvements over previous machine learning and hand-tuned efforts, including greater accuracy (e.g., at high-fluence relevant for extending the life of present reactors), wider domain of applicability (e.g., including a wide-range of compositions), uncertainty quantification, and online accessibility for easy use by the community. These improvements provide a model with significant new capabilities, including the ability to easily and accurately explore compositions, flux, and fluence effects on RPV steel embrittlement for the first time. Furthermore, our detailed comparisons show our approach improves on the leading American Society for Testing and Materials (ASTM) E900-15 standard model for RPV embrittlement on every metric we assessed, demonstrating the efficacy of machine learning approaches for this type of highly demanding materials property prediction. [ABSTRACT FROM AUTHOR]

Recent trends in the aluminum industry toward increasing the recycling rate of aluminum alloys have led to difficulties in controlling the formation of intermetallic compounds (IMCs). The up-to-date investigations have revealed that ultrasonic irradiation is a promising tool to refine and modify the intermetallic compounds formed in the melt before or during casting, and the reported mechanisms include ultrasound-assisted nucleation and fragmentation of compounds. This work presents results concerning the modification effect of ultrasound on model Al 3 Zr compounds with emphasis on the effect of vibration amplitudes. The results reveal that needle-like Al 3 Zr compounds can be significantly modified to thicker shape when amplitude increases from 38 µm to 48 µm, and then change to more rounded shape with the further increase of amplitude. Theoretical consideration and numerical simulation show that in addition to the above-mentioned mechanisms, cavitation-induced heat generation and mircrojet-driven mass transfer are also of prime importance in controlling the morphology and growth of IMCs. • A wide range of ultrasound vibration amplitude is examined. • Needle-like Al 3 Zr compounds can be significantly modified to more rounded shape when amplitude increases. • Behavior of cavitation bubble near compound particle is simulated numerically. • Cavitation-induced heat generation and microjet-driven mass transfer play a prominent role in controlling the morphology and growth of primary Al 3 Zr compounds. [ABSTRACT FROM AUTHOR]

The resistance to transcription factor-mediated reprogramming into pluripotent stem cells is one of the distinctive features of cancer cells. Here we dissect the profiles of reprogramming factor binding and the subsequent transcriptional response in cancer cells to reveal its underlying mechanisms. Using clear cell sarcomas (CCSs), we show that the driver oncogene EWS/ATF1 misdirects the reprogramming factors to cancer-specific enhancers and thereby impairs the transcriptional response toward pluripotency that is otherwise provoked. Sensitization to the reprogramming cue is observed in other cancer types when the corresponding oncogenic signals are pharmacologically inhibited. Exploiting this oncogene dependence of the transcriptional "stiffness," we identify mTOR signaling pathways downstream of EWS/ATF1 and discover that inhibiting mTOR activity substantially attenuates the propagation of CCS cells in vitro and in vivo. Our results demonstrate that the early transcriptional response to cell fate perturbations can be a faithful readout to identify effective therapeutics targets in cancer cells. [Display omitted] • Driver oncogenic signals impede transcriptional responses to reprogramming TFs • Reprogramming TFs are misdirected by oncogenic signals to bind cancer cell enhancers • A screening platform based on the oncogene dependence of the impediment is developed • The screening identifies mTOR signaling as a therapeutic target in CCS In general, cancer cells are resistant to reprogramming. Ito et al. show that this is due to misdirection of reprogramming factors by oncogenic driver signals. Exploiting this finding, they established a novel screening platform that identifies mTOR signaling as a potential therapeutic target in CCS. [ABSTRACT FROM AUTHOR]

[Display omitted] • Design strategy of phase change material properties are developed for low-energy memory application. • Low operation energy condition is explored automatically through Bayesian optimization. • Operation energy is lowered by decreasing thermal conductivity, ratio of volume resistance to contact resistance and phase change temperature. • According to the developed design strategy, operation energy of typical Ge-Sb-Te can be decreased to less than 1/100 in phase change memory application. Aiming at reducing energy consumptions in data writing, the development of new memory materials is highly required. To develop new phase change materials (PCMs) with extremely low operation energy used in non-volatile memory, such as storage-class memory, we performed Bayesian optimization for the physical properties of PCMs through numerical simulations. In this numerical simulation, the electrical potential and temperature distribution were solved simultaneously. It was found that a PCM with low thermal conductivity, low melting temperature, and low ratio of contact resistance to volumetric resistance results in a low operation energy of a PCM-based memory application. Finally, we developed a design strategy for PCMs. New PCMs should be developed by lowering the operation energy E , described as E = κ (1 + C)Δ T /Δ z , where κ is the thermal conductivity of the PCM, Δ T is the melting temperature, C is the ratio of contact resistance to the volumetric resistance, and Δ z is the thickness of the PCM. The present results clarify the relationship between thermal and electrical properties for lowering operation energy ever hidden in previous studies. According to the design strategy, an operation energy in phase change memory application can be decreased to less than 1/100 compared with conventional Ge-Sb-Te compounds. [ABSTRACT FROM AUTHOR]

Human induced pluripotent stem cells (hiPSCs) show variable differentiation potential due to their epigenomic heterogeneity, whose extent/attributes remain unclear, except for well-studied elements/chromosomes such as imprints and the X chromosomes. Here, we show that seven hiPSC lines with variable germline potential exhibit substantial epigenomic heterogeneity, despite their uniform transcriptomes. Nearly a quarter of autosomal regions bear potentially differential chromatin modifications, with promoters/CpG islands for H3K27me3/H2AK119ub1 and evolutionarily young retrotransposons for H3K4me3. We identify 145 large autosomal blocks (≥100 kb) with differential H3K9me3 enrichment, many of which are lamina-associated domains (LADs) in somatic but not in embryonic stem cells. A majority of these epigenomic heterogeneities are independent of genetic variations. We identify an X chromosome state with chromosome-wide H3K9me3 that stably prevents X chromosome erosion. Importantly, the germline potential of female hiPSCs correlates with X chromosome inactivation. We propose that inherent genomic properties, including CpG density, transposons, and LADs, engender epigenomic heterogeneity in hiPSCs. [Display omitted] • Two distinct epigenomic states stably maintain X inactivation in hiPSCs • X-chromosome-wide propagation of H3K9me3 can occur in XIST -downregulated hiPSCs • Epigenomic heterogeneity on autosomes is enriched in non-genic/repressive regions • Heterogenous H3K9me3 domains are associated with nuclear lamina in somatic cells Yokobayashi et al. find that, in addition to imprinting and X-chromosome variations, CpG density, transposons, and H3K9me3-associated large domains contribute to the emergence or retention of epigenomic heterogeneity in hiPSCs. They identify differential epigenomic states that correlate with the in vitro germ cell differentiation potential of hiPSCs. [ABSTRACT FROM AUTHOR]

In-service exposure to high-energy neutrons embrittles reactor pressure vessel (RPV) steels. An increase in the yield stress (Δσ y) results in a corresponding increase in the brittle to ductile transition temperature (ΔT c). Most existing models underpredict ΔT c at higher fluence following accelerated irradiations in test reactors. High fluence, up to 1020 n/cm2 in some cases, will be reached over extended RPV vessel operation of 80 years, or more, at low service flux. Embrittlement has been extensively studied in accelerated, higher flux test reaction irradiations. However, the use of test reactor data naturally raises the question of flux effects. This study used a machine learning approach trained on a set of hardening data, covering a wide range of flux, fluence, and steel compositions to determine the interactive effects of both irradiation and material variables on Δσ y. The analysis included machine learning-based cross-plots of the variable dependence of Δσ y for six core steels (i.e., CM6, LC, LD, LG, LH, and LI), with controlled differences in their Cu and Ni contents. A primary objective is to evaluate an effective to actual fluence (ɸt e /ɸt) ratio, as a function of flux, fluence, and steel composition. This is information critical to properly use intermediate flux-high fluence data in calibrating a low flux-high fluence embrittlement model. The predicted ɸt e /ɸt is reasonably consistent with estimates previously derived from a physics-based solute recombination trap model. [Display omitted] [ABSTRACT FROM AUTHOR]

Development of a universal influenza vaccine that can provide robust and long-lasting protection against heterologous infections is a global public health priority. A variety of vaccine antigens are designed to increase the antigenicity of conserved epitopes to elicit cross-protective antibodies that often lack virus-neutralizing activity. Given the contribution of antibody effector functions to cross-protection, adjuvants need to be added to modulate antibody effector functions as well as to enhance antibody quantity. We previously showed that post-fusion influenza vaccine antigens elicit non-neutralizing but cross-protective antibodies against conserved epitopes. Here, using a murine model, we comparably assessed the adjuvanticity of the newly developed SA-2 adjuvant containing a synthetic TLR7 agonist DSP-0546 and squalene-based MF59 analog as representative Th1- or Th2-type adjuvants, respectively. Both types of adjuvants in the post-fusion vaccine comparably enhanced cross-reactive IgG titers against heterologous strains. However, only SA-2 skewed the IgG subclass into the IgG2c subclass in association to its Th1-polarizing nature. SA-2-enhanced IgG2c responses exhibited antibody-dependent cellular cytotoxicity against heterologous virus strains, without cross-neutralizing activity. Eventually, the SA-2-adjuvanted vaccination provided protection against lethal infection by heterologous H3N2 and H1N1 viruses. Together, we conclude that the combination with a SA-2 is advantageous for enhancing the cross-protective capability of post-fusion HA vaccines that elicit non-neutralizing IgG antibodies. [ABSTRACT FROM AUTHOR]

Endothelial cells (ECs) line blood vessels and serve as a niche for hematopoietic stem and progenitor cells (HSPCs). Recent data point to tissue-specific EC specialization as well as heterogeneity; however, it remains unclear how ECs acquire these properties. Here, by combining live-imaging-based lineage-tracing and single-cell transcriptomics in zebrafish embryos, we identify an unexpected origin for part of the vascular HSPC niche. We find that islet1 (isl1)-expressing cells are the progenitors of the venous ECs that constitute the majority of the HSPC niche. These isl1 -expressing cells surprisingly originate from the endoderm and differentiate into ECs in a process dependent on Bmp-Smad signaling and subsequently requiring npas4l (cloche) function. Single-cell RNA sequencing analyses show that isl1 -derived ECs express a set of genes that reflect their distinct origin. This study demonstrates that endothelial specialization in the HSPC niche is determined at least in part by the origin of the ECs. [Display omitted] • islet1 (isl1) lineage endothelial cells form part of the vascular HSPC niche in zebrafish • isl1 -expressing endothelial progenitors originate from the endoderm • Endothelial cell specialization in HSPC niche is in part determined by their origin Nakajima, Ishikawa, et al. identify an endothelial lineage that originates from the endoderm and specifically contributes to the caudal vein in zebrafish. These endothelial cells, which derive from islet1 -expressing progenitors, form part of the vascular HSPC niche where they play an essential role. [ABSTRACT FROM AUTHOR]

Ameloblastic fibrosarcoma (AFS) is the most common odontogenic sarcoma, but the incidence is relatively low, and its molecular biology is poorly understood. We experienced a young female patient with a rapidly growing soft tissue tumor of the left maxilla, which eventually occupied the left side of the oral cavity. Histologically, the tumor mainly consisted of a proliferation of atypical spindle to polygonal cells without any specific differentiation, but a small number of benign odontogenic epithelial foci mainly in the tumor periphery were also noted; thus, a diagnosis of AFS was made. We performed whole-exome sequencing (WES) on the tumor to investigate its molecular features and identify therapeutic options. We found that the tumor harbored EGFR exon 20 insertions and MDM2 amplification; the former may be a target for newly developed tyrosine kinase inhibitors in case of recurrence. To the best of our knowledge, this is the first case of AFS for which WES was performed and with EGFR mutation. Our case provides new genetic information on AFS and suggests that comprehensive genetic analysis can clarify the molecular biology in rare cancers, potentially leading to the proposal of therapeutic strategies. [ABSTRACT FROM AUTHOR]

We have investigated magnetic properties for reactor pressure vessel model alloys with variable Cu contents, subjected to neutron irradiation up to a fluence of 9 × 10 19 n cm − 2. Unlike a monotonic increase of microhardness with neutron fluence, the major-loop coercivity decreases at a higher fluence and the decrease becomes larger for the alloy containing a higher amount of Cu. The measurements of first-order reversal curves (FORCs) for the high-Cu alloy show that the position of the FORC distribution peak shifts toward a lower coercivity just after neutron irradiation, followed by a slight increase, associated with the broadening along both the coercivity and interaction field axes. The results can be explained by the enhancement of magnetic inhomogeneity in a matrix due to Cu precipitation and an increasing magnetostatic interaction between local magnetic regions with different coercivity. The magnetic method using FORCs can be a possible technique which provides in-depth information on microstructural changes due to neutron irradiation, which is not obtained by measurements of a conventional major hysteresis loop. [ABSTRACT FROM AUTHOR]

This study numerically investigates the mechanism of vibration damping in woven composite structures using a decoupled multi-scale simulation scheme that considers the macroscopic woven structure consisting of bundles and resin-rich regions, as well as the microscopic structure in the bundles made of fiber and resin. For efficient macroscopic modeling of complicated woven structures, the embedded element technique is introduced to utilize separate meshes for bundles and resin regions. A special treatment is introduced for volumetric integration in the mesh overlapped between bundle and resin regions, which is required to calculate the strain energy and modal damping ratio of the entire woven structure. Using the developed scheme, the natural frequencies and damping ratios of braided and laminated composite cylinders are investigated. By comparing the vibration properties of two braided composites with different braided angles and two unidirectional laminates with different fiber volume fractions, the effects of the fiber volume fraction, braided angle, and out-of-plane waviness on vibration properties are discussed. Based on the mode shape and resultant energy dissipation within each bundle and resin-rich region, the braided composite with a large braided angle exhibited the best damping properties, mainly owing to the in-plane shear deformation in the crimped braided bundles. [ABSTRACT FROM AUTHOR]

Thermoplastic elastomers (TPEs) have long been used in a wide range of industries. However, most existing TPEs are petroleum-derived polymers. To realize environmentally benign alternatives to conventional TPEs, cellulose acetate is a promising TPE hard segment because of its sufficient mechanical properties, availability from renewable sources, and biodegradability in natural environments. Because the degree of substitution (DS) of cellulose acetate governs a range of physical properties, it is a useful parameter for designing novel cellulose acetate-based TPEs. In this study, we synthesized cellulose acetate-based ABA-type triblock copolymers (AcCel x - b -PDL- b -AcCel x) containing a celloologosaccharide acetate hard A segment (AcCel x , where x is the DS; x = 3.0, 2.6, and 2.3) and a poly(δ -decanolactone) (PDL) soft B segment. Small-angle X-ray scattering showed that decreasing the DS of AcCel x - b -PDL- b -AcCel x resulted in the formation of a more ordered microphase-separated structure. Owing to the microphase separation of the hard cellulosic and soft PDL segments, all the AcCel x - b -PDL- b -AcCel x samples exhibited elastomer-like properties. Moreover, the decrease in DS improved toughness and suppressed stress relaxation. Furthermore, preliminary biodegradation tests in an aqueous environment revealed that the decrease in DS endowed AcCel x - b -PDL- b -AcCel x with greater biodegradability potential. This work demonstrates the usefulness of cellulose acetate-based TPEs as next-generation sustainable materials. [Display omitted] [ABSTRACT FROM AUTHOR]

• The phenomena occurring near or on the melt free surface during ultrasonic treatment for molten aluminum are examined. • Ultrasonic treatment can greatly promote the formation of alumina particles on the melt surface around sonotrode. • A part of formed alumina particles can be entrained from the free surface into the melt bulk. • The entrained alumina particles can serve as nucleation sites for primary Al3Zr compounds. Although the ultrasonic treatment of molten aluminum has been studied for long period, there is still much to be revealed for this process. Many studies have focused on the investigation of acoustic cavitation and streaming under the horn tip and their effects on the treatment efficiency. However, to the best of our knowledge, no attempt has been done to explain phenomena occurring near or on the melt free surface. Thus, the goal of this study is to investigate phenomena occurring at the free surface during ultrasound irradiation and clarify their possible influence on the ultrasound treatment performance. The results of high temperature and water model experiments reveal that ultrasound irradiation significantly promotes the formation of alumina particles on the melt free surface around sonotrode, and part of these particles can be entrained into aluminum melts. Furthermore, TEM observation results suggested that the entrained alumina inclusions can serve as nucleation sites for the primary Al 3 Zr compounds. Most importantly, the oxidation and entrainment of particles from free surface are likely to be controllable by the immersion depth of sonotrode into molten aluminum. [ABSTRACT FROM AUTHOR]

Alzheimer disease (AD) is an irreversible, progressive brain disease. Amyloid β plays a critical role in AD development. Some Chinese traditional medicines, such as the fossilized plant resin, amber, have been applied as mental stabilizers. However, the effects of amber on AD pathogenesis remain unknown. Therefore, we aimed to determine the potential of amber extract for treating AD by evaluating its effects on amyloid-β (1-42) (Aβ (1-42))-induced neuronal cell death. We measured levels of ROS, Bcl-2, and Bax mRNA, and found that amber extract decreased Aβ (1-42)-induced cell apoptosis via the reactive oxygen species (ROS)-mediated mitochondrial pathway. Amber extract also decreased β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and increased microtubule-associated proteins 1A/1B light chain 3B (LC3II) and Beclin 1. These findings suggested that amber extract protects neuronal cells against Aβ (1-42)-induced cell apoptosis by upregulating autophagy and downregulating BACE1. [Display omitted] • Amber extract protects against Aβ (1-42)-induced cytotoxicity in SHSY5Y cells. • Amber extract can downregulate amyloid-β1–42-induced BACE1 expression in SHSY5Y cells. • Amber extract promotes autophagy in SHSY5Y cells. [ABSTRACT FROM AUTHOR]

The effect of deuteration of polymeric nanofibers (NFs) on their structure and thermal and mechanical properties was investigated. Three types of polyamides (PA; PA66, PA6, and PA11) NFs were prepared by electrospinning from solutions with non-deuterated or deuterated solvents and subsequently characterized. In the NFs prepared with deuterated solvents, partial hydrogen–deuterium (H–D) exchange occurred in the amide linkages of the polymers, leading to improved thermal and mechanical properties. Further, partial deuteration of amide linkages in all the PAs slightly increased the NF melting and glass transition points and substantially improved the Young's moduli and tensile strengths of the NF sheets by 1.2–1.3 times. Additionally, the degree of crystallinity improved due to the deuteration effect. The results clearly indicate that this facile, solution processing approach based on H–D exchange in the amide linkages is promising for improving the properties of polymer NFs. [Display omitted] • First report on ambient stable deuteration effect on polymeric nanofiber properties. • Facile hydrogen bond tuning in electrospun polyamide nanofibers. • Solution phase H–D exchange partially replaces H in the amide linkages with D. • Improved thermal and mechanical properties achieved for all polyamide nanofibers. [ABSTRACT FROM AUTHOR]