Polysorbate identity and quantity dictate the extensional flow properties of protein-excipient solutions

While protein medications are promising for treatment of cancer and autoimmune diseases, challenges persist in terms of development and injection stability of high-concentration formulations. Here, the extensional flow properties of protein-excipient solutions are examined via dripping-onto-substrate extensional rheology, using a model ovalbumin (OVA) protein and biocompatible excipients polysorbate 20 (PS20) and 80 (PS80). Despite similar PS structures, differences in extensional flow are observed based on PS identity in two regimes: at moderate total concentrations where surface tension differences drive changes in extensional flow behavior, and at small PS:OVA ratios, which impact the onset of weakly elastic flow behavior. Undesirable elasticity is observed in ultra-concentrated formulations, independent of PS identity; higher PS contents are required to observe these effects than in analogous polymeric excipient solutions. These studies reveal novel extensional flow behaviors in protein-excipient solutions, and provide a straightforward methodology for assessing the extensional flow stability of new protein-excipient formulations.     

不同进水流速对泵站进水池漩涡的影响

为探究泵站进水流速大小与泵站进水池水流流态、漩涡的产生与发展变化规律,结合泵站实际运行情况,建立引渠、前池、进水池和进水管的泵站物理模型和湍流数学模型,采用VOF模型和非定常的SST k-ω湍流模型对9种不同流速的泵站进水水流特性进行数值模拟,分析不同进水流速的泵站进水池水流流场分布、漩涡涡量的变化及分布规律。研究结果表明:当进水流速为0.322 2～0.564 2 m/s时,泵站表面漩涡的强度随进水流速的增大而增强:当进水流速为0.322 2～0.401 6 m/s时,进水池出现Ⅲ、Ⅳ型漩涡;当进水流速为0.483 5 m/s时,进水池出现Ⅴ型漩涡;当进水流速为0.520 8～0.564 2 m/s时,进水池出现Ⅵ型漩涡。将数值计算结果与模型试验结果进行对比,两者基本吻合。研究结果可为泵站工程设计提供参考。     

Thermal destratification of cryogenic liquid storage tanks by continuous bubbling of gases

This paper focuses on thermal destratification and pressurisation inside thermally stratified storage tanks by continuous gas bubbling. The primary purpose of doing these studies is to better understand the effect of bubble dynamics on thermal destratification and quantify the extent of destratification. The volume of fluid and interface compression method of OpenFOAM CFD code is utilised for the present analysis. Different values of inlet gas velocities (V_g), orifice diameters (d_o), and arrangement of the orifices in triangular and square fashion with different pitches (p/d_o) are considered. In addition, the effect of gravitational forces (g/g_e) on thermal destratification is also reported. For all these cases, the effectiveness of thermal destratification is quantified in terms of a newly defined parameter, the destratification index (I_d). For V_g = 1 m/s, the I_d value is maximum compared to lower V_g values. It is seen that when the gas velocity increased from 0.3 m/s to 1.0 m/s, the average effectiveness in thermal destratification (I_davg) and pressure at the ullage increased by 44.38% and by 64.81%, respectively. The I_davg and pressure at ullage increased by 96.29% and 14.91%, respectively, when the g/g_e ratio changed from 0.3 to 3. Compared to the triangular arrangement with p/d_o = 10, the calculated I_davg increased by 30.67% when gas inlets were arranged with a square pitch of 10. For p/d_o = 4, 6 and 8, the increments in I_davg are of the order of 12.86%, 19.43% and 21.92%, respectively, for gas inlets arranged in a square fashion as compared to the triangular arrangement. It is found that continuous bubbling with gas inlets arranged in square pitch p/d_o = 10 gives higher effectiveness in thermal destratification. Thus, by these studies, one can develop a thermal destratification mechanism with continuous bubbling for optimum performance. Also, these studies give an overall idea of sparger design for getting the correct gas flow rate for thermal destratification within the cryogenic liquid storage tanks.     

Finite element limit analysis of load-bearing performance of reinforced slopes using a non-associated flow rule

This paper presents a numerical study on the load-bearing performance of reinforced slopes under footing load using a finite element limit analysis (FELA) method where a non-associated flow rule is assumed in the analysis. The method was validated against results from full-scale model tests and a limit equilibrium (LE) analytical method. A series of parametric analyses was subsequently carried out to examine the influences that the soil dilation angle, footing location, and reinforcement design (i.e. length, tensile strength, and vertical spacing) could have on the load-bearing performance of reinforced slopes. Results indicate that dilation angle has a significant influence on the predicted magnitudes of bearing capacity, slope deformation, and mobilized reinforcement load. The predicted values of bearing capacity using the FELA are smaller than those from the Meyerhof's analytical method for unreinforced semi-infinite foundation, especially for larger friction angle values. Additionally, the ultimate bearing capacity of the slope and its corresponding horizontal deformation increase with the reinforcement tensile strength. Finally, the slip planes under the applied footing load are found to be y-shaped and primarily occur in the upper half of the slope.     

Coupling Interrupted Fischer and Multicomponent Joullié-Ugi to Chase Chemical Diversity: from Batch to Sustainable Flow Synthesis of Peptidomimetics

The generation of peptidomimetic substructures for medicinal chemistry purposes requires effective and divergent synthetic methods. We present in this work an efficient flow process that allows quick modulation of reagents for Joullié-Ugi multicomponent reaction, using spiroindolenines as core motifs. This sterically hindered imine equivalent could successfully be diversified using various isocyanides and amino acids in generally good space-time yields. A telescoped flow process combining interrupted Fischer reaction for spiroindolenine synthesis and subsequent Joullié-Ugi-type modification resulted in product formation in very good overall yield in less than 2 hours compared to 48 hours required in batch mode. The developed protocol can be seen as a general tool for rapid and facile generation of peptidomimetic compounds. We also showcase preliminary biological assessments for the prepared compounds.     

Prediction models for multiphase-flow-induced corrosion of API X80 steel in CO2/H2S environment

In the offshore oil and gas industry, mainly focusing on the use of rigid or flexible pipes of subsea infrastructure applied to risers or flowlines, one of the greatest difficulties is the interpretation of the combined effects of the various correlated phenomena (hydrodynamic effects of intermittent flow, the effects of corrosivity of the environment in addition to variations in pressure, temperature, and dynamic loading). On the basis of this scenario, defining the degree of severity of each of the correlated system variables becomes of fundamental importance for establishing reliable criteria for selecting materials for subsea application. The established flow pattern directly affects the corrosion rate (or the pipe material mass loss), but the balance of other variables including possible changes in the physical and transported fluid chemical properties may increase the damage up to an order of magnitude, which is a piece of information normally not foreseen in design criteria. Therefore, to improve the understanding of the corrosion study influenced by multiphase flow, a testing loop was designed and assembled at the Corrosion and Protection Laboratory of the Institute for Technological Research, in which API X80 steel coupons were positioned in locations with a 0° and 45° inclinations. Tests were conducted by varying the partial pressure of the gaseous phase containing blends of CO₂ and H₂S with N₂ balance, mixed with the liquid phase containing light oil and heavy oil in water with salinity (NaCl)-simulating oil well conditions with 80% water cut. The main objective of this study is to establish models that can predict the corrosion intensity in conditions close to those obtained experimentally. To achieve results, the multiple regression and Box–Cox transformation methods were applied. These models will make possible damage prediction and optimization of matrix parameters for the multiphase-loop test.     

Contribution of Drugs Interfering with Protein and Cell Wall Synthesis to the Persistence of Pseudomonas aeruginosa Biofilms: An In Vitro Model

The occurrence of Pseudomonas aeruginosa (PA) persisters, including viable but non-culturable (VBNC) forms, subpopulations of tolerant cells that can survive high antibiotic doses, is the main reason for PA lung infections failed eradication and recurrence in Cystic Fibrosis (CF) patients, subjected to life-long, cyclic antibiotic treatments. In this paper, we investigated the role of subinhibitory concentrations of different anti-pseudomonas antibiotics in the maintenance of persistent (including VBNC) PA cells in in vitro biofilms. Persisters were firstly selected by exposure to high doses of antibiotics and their abundance over time evaluated, using a combination of cultural, qPCR and flow cytometry assays. Two engineered GFP-producing PA strains were used. The obtained results demonstrated a major involvement of tobramycin and bacterial cell wall-targeting antibiotics in the resilience to starvation of VBNC forms, while the presence of ciprofloxacin and ceftazidime/avibactam lead to their complete loss. Moreover, a positive correlation between tobramycin exposure, biofilm production and c-di-GMP levels was observed. The presented data could allow a deeper understanding of bacterial population dynamics during the treatment of recurrent PA infections and provide a reliable evaluation of the real efficacy of the antibiotic treatments against the bacterial population within the CF lung.