Search

Currently there is a limited understanding for the optimal combination of immune checkpoint inhibitor and chemotherapy for patients with metastatic triple-negative breast cancer (mTNBC). Here we evaluate the safety, efficacy, and immunogenicity of a phase I trial for patients with mTNBC treated with pembrolizumab plus doxorubicin. Patients without prior anthracycline use and 0–2 lines of prior systemic chemotherapies received pembrolizumab and doxorubicin every 3 weeks for 6 cycles followed by pembrolizumab maintenance until disease progression or intolerance. The primary objectives were safety and objective response rate per RECIST 1.1. Best responses included one complete response (CR), five partial responses (PR), two stable disease (SD), and one progression of disease (PD). Overall response rate was 67% (95% CI 13.7%, 78.8%) and clinical benefit rate at 6 months was 56% (95% CI 21.2%, 86.3%). Median PFS was 5.2 months (95% CI 4.7, NA); median OS was 15.6 months (95% CI 13.3, NA). Grade 3–4 AEs per CTCAE 4.0 were neutropenia n = 4/10 (40%), leukopenia n = 2/10 (20%), lymphopenia n = 2/10 (20%), fatigue n = 2/10 (20%), and oral mucositis n = 1/10 (10%). Immune correlates showed increased frequencies of circulating CD3 + T cells (p = 0.03) from pre-treatment to cycle 2 day 1 (C2D1). An expansion of a proliferative exhausted-like PD-1 + CD8 + T cell population was identified in 8/9 patients, and exhausted CD8 + T cells were significantly expanded from pre-treatment to C2D1 in the patient with CR (p = 0.01). In summary, anthracycline-naïve patients with mTNBC treated with the combination of pembrolizumab and doxorubicin showed an encouraging response rate and robust T cell response dynamics. Trial registration: NCT02648477. [ABSTRACT FROM AUTHOR]

The crystallization processes of titanates are central to the fabrication of optical and electrical crystals and glasses, but their rich polymorphism is not fully understood. Here, we show when and how polymorphic selection occurs during the crystallization of barium titanate (BaTiO3, BT) using in situ high energy synchrotron X-ray diffraction and ab initio molecular dynamic simulation. An anomalous structure transition is found in molten BT during cooling across the cubic-hexagonal transition temperature, which enables nucleation selection of BT by manipulating the undercooling: a cubic phase is preferred if nucleation is triggered at large undercooling, whereas a hexagonal phase is promoted at small undercooling. We further reveal that the nucleation selection between the cubic and the hexagonal phase is regulated by the intrinsic structure property of the melt, in particular, the degree of polymerization between Ti-O polyhedra. These findings provide an innovative perspective to link the polymorphic crystallization to the non-isomorphic structure transition of the melt beyond the conventional cognition of structural heredity. The crystallization processes of titanates are central to the fabrication of optical and electrical crystals and glasses, but their rich polymorphism is not fully understood. Here, authors identify when and how polymorphic selection takes place during the crystallization of an undercooled barium titanate melt using aerodynamic levitation, in situ time resolved high energy X-ray diffraction and ab initio molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

Effect of Si on the growth behavior of the Fe2Al5 phase formed at the Al-xSi(liquid)/Fe(solid) interface during holding was investigated by a synchrotron radiation real-time imaging technique. Results show that growth of the Fe2Al5 phase is accompanied by its simultaneous dissolution into the melt. Addition of Si inhibits the growth of Fe2Al5 to reduce its thickness and change its morphology. The growth and dissolution kinetics of the Fe2Al5 phase are discussed. [ABSTRACT FROM AUTHOR]

The morphological transition and growth mechanism of Al3Ni phase during solidification at the liquid Al/solid Ni interface was investigated through synchrotron radiography. The remelted peritectic Al3Ni is dominated by coalescence of adjacent grains and precipitation with the morphology changing from columnar, irregular, scallop type to faceted shape. The hollow proeutectic Al3Ni is formed on a solid base. The increased r/R ratio and steep variation lead to the change from regular to irregular hollowness with asymmetrical shape. [ABSTRACT FROM AUTHOR]

Synchrotron X-ray radiography was utilized to in situ study the Ni dissolution during holding and growth behavior of intermetallic compounds (IMCs) during solidification at the liquid Al/solid Ni interface, and synchrotron tomography was used to reconstruct the diversified Al3Ni phases. The dissolution and IMC growth was quantitatively analyzed. During holding, the solid Ni dissolved heterogeneously into liquid Al, and the quantification of Ni concentration was obtained from intensity values. The layered Al3Ni2 formed at the interface during solidification, following by columnar and needle-like Al3Ni. The growth of Al3Ni2 layer followed a parabolic law, being controlled by bulk diffusion mechanism. The peritectic and proeutectic Al3Ni grew along the length obviously at the early stage and coarsened in the late stage. The proeutectic Al3Ni phase had a stronger [001] orientation than peritectic Al3Ni phase. [ABSTRACT FROM AUTHOR]

NaZn-type La(Fe,Si) alloy is a promising magnetocaloric material for solid refrigeration. Currently, several days of high-temperature annealing are typically required to transform both the α-Fe phase and LaFeSi phase to a La(Fe,Si) phase by diffusion. However, no bulk casting has yet been reported. In this study, directional solidification is used to prepare LaFeSi alloys with a dual-phase microstructure consisting of α-Fe and LaFeSi phases. It was found that the volume fraction of La(Fe,Si) phase in directionally solidified LaFeSi alloys can be increased to ~62 pct. It was also found that the volume fraction of the La(Fe,Si) phase is dependent primarily on the temperature gradient at different growth rates, which can be the result of their wide temperature range between solidus and liquidus. A significant Si segregation was observed in directionally solidified LaFeSi alloys. Furthermore, the solidification path was discussed, focusing on the volume fraction increase of the La(Fe,Si) phase by directional solidification. [ABSTRACT FROM AUTHOR]

An intermittency model that is formulated in local variables is proposed for representing bypass transition in Reynolds-Averaged Navier-Stokes (RANS) computations. No external data correlation is used to fix transition. Transition is initiated by diffusion, and a source term carries it to completion. A sink term is created to predict the laminar region before transition, then it vanishes in the turbulent region. Both the source and sink are functions of a wall-distance Reynolds number and turbulence scale. A modification is introduced to predict transition in separated boundary layers. The transition model is incorporated with the k− ω RANS model. The present model is implemented into a general purpose, computational fluid dynamics (CFD) code. The model is validated with several test cases. Decent agreement with the available data is observed in a range of flows. [ABSTRACT FROM AUTHOR]

Geosmin (GSM) and 2-methylisoborneol (2-MIB) have been identified as the major taste and odor-causing compounds in drinking water obtained from surface water. Carboxylated multi-walled carbon nanotubes (C-MWCNs) were developed for the highly efficient removal of GSM and 2-MIB from water owing to their unique large surface area, well-defined pore size, and high pore volume. Besides, the carboxyl group on the surface of C-MWCNs can improve the adsorption capacity of GSM and 2-MIB which each contain one hydroxyl group. Each adsorption of 200 cm 1 μg/dm of GSM (or 2-MIB) onto 40 mg/dm of C-MWCNs reached equilibrium within 120 min. This agreed well with the Langmuir adsorption model with maximum adsorption capacities of 23.56 and 23.52 μg/g for GSM and 2-MIB. The adsorption rates of GSM and 2-MIB on C-MWCNs fit pseudo-second-order kinetic models ( R > 0.99), which suggest that the adsorption process could be a rate-limiting step. Thermodynamic studies illustrated that the adsorption process was endothermic and spontaneous. C-MWCNs are able to remove over 90 % of GSM and 2-MIB in 200 cm of solution containing 1 μg/dm GSM (or 2-MIB) under optimized conditions. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Salt (NaCl) is a common physiological stressor of plants. To better understand how germinating seeds respond to salt stress, we examined the changes that occurred in the proteome of maize seeds during NaCl-treated germination. Phenotypically, salt concentrations less than 0.2 M appear to delay germination, while higher concentrations disrupt development completely, leading to seed death. The identities of 96 proteins with expression levels altered by NaCl-incubation were established using 2-DE-MALDI-TOF-MS and 2-DE-MALDI-TOF-MS/MS. Of these 96 proteins, 79 were altered greater than twofold when incubated with a 0.2 M salt solution, while 51 were altered when incubated with a 0.1 M salt solution. According to their functional annotations in the Swiss-Prot protein-sequence databases, these proteins are mainly involved in seed storage, energy metabolism, stress response, and protein metabolism. Notably, the expression of proteins that respond to abscisic acid signals increased in response to salt stress. The results of this study provide important clues as to how NaCl stresses the physiology of germinating maize seeds. [ABSTRACT FROM AUTHOR]