Imbibition oil recovery of single fracture-controlled matrix unit: Model construction and numerical simulation

The fracture-controlled matrix unit is commonly found in low-permeability fractured reservoirs. Due to the permeability difference between the fracture system and the matrix system, a large amount of oil will remain in the matrix during traditional water injection development, thus limiting reservoir productivity. However, the special imbibition mode of the fracture-controlled matrix unit provides a breakthrough for secondary oil recovery. In this paper, based on the model of single fracture-controlled matrix unit, the dynamic production process of fractured reservoir is studied by the numerical simulation method. The numerical simulation of the imbibition oil production is carried out on the two-point well model by using the method of huff and puff injection. The results show that imbibition is the main mechanism in the middle and late stages of oil recovery from fractured reservoirs. The water in the fracture is absorbed into the matrix by capillary force and the oil is replaced; in this way, imbibition can increase the recovery rate by 20%. The findings provide a basis for the further study of the fracture-controlled matrix unit and imbibition.Cited as: Liu, Q., Liang, B., Liu, J., Sun, W., Lei, Y. Imbibition oil recovery of single fracture-controlled matrix unit: Model construction and numerical simulation. Capillarity, 2022, 5(2): 32-40. https://doi.org/10.46690/capi.2022.02.0

Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2

大多数真核生物的体细胞是二倍体，即仅含有两组染色体，分别遗传自父本和母本。而一些特定组织如心脏、肝脏等就含有多倍体细胞，特别是肝脏组织含有较高比例的四、八倍体等多倍体细胞。肝脏是人体的重要解毒器官，同时酒精、肝炎病毒等毒性物质或毒性代谢物容易诱发肝细胞的基因突变，多倍体被认为有利于提供代偿性的正常基因来维持肝脏稳态。然而肝脏受损后，多倍体细胞将会受胁迫进行增殖，再生修复受损的肝组织。因此研究机体调控多倍体细胞产生及多倍体细胞进行细胞分裂的调控机理对于理解肝癌的发病机理和肝癌的治疗至关重要。Hippo信号通路在调节组织成体干细胞的分化和增殖，调控器官再生与尺寸大小中具有重要作用。深入研究发现, Hippo信号通路下游效应分子YAP通过AKT-SKP2信号促进二倍体细胞向多倍体转化及多倍体细胞的生长增殖。本项研究阐明了Hippo缺失及YAP激活促进多倍体细胞产生及增殖作为肝癌发生发展中的一个重要机制，为肝癌诊疗提供了新的策略。 周大旺，博士，厦门大学生命科学学院教授、副院长、国家杰出青年基金获得者。【Abstract】Polyploidy can lead to aneuploidy and tumorigenesis. Here, we report that the Hippo pathway effector Yap promotes the diploid-polyploid conversion and polyploid cell growth through the Akt-Skp2 axis. Yap strongly induces the acetyltransferase p300-mediated acetylation of the E3 ligase Skp2 via Akt signaling. Acetylated Skp2 is exclusively localized to the cytosol, which causes hyper-accumulation of the cyclin-dependent kinase inhibitor p27, leading to mitotic arrest and subsequently cell polyploidy. In addition, the pro-apoptotic factors FoxO1/3 are overly degraded by acetylated Skp2, resulting in polyploid cell division, genomic instability, and oncogenesis. importantly, the depletion or inactivation of Akt or Skp2 abrogated Hippo signal deficiency-induced liver tumorigenesis, indicating their epistatic interaction. Thus, we conclude that Hippo-Yap signaling suppresses cell polyploidy and oncogenesis through Skp2.该研究工作获得了国家自然科学基金委、国家重点基础研究发展计划(973)项目、青年千人计划和中央高校基本科研基金的资助。 The Yap (S127A) transgenic mice were kindly provided by Dr. Fernando Camargo from Harvard Medical School, Boston, MA. D.Z. and L.C. were supported by the National Natural Science Foundation of China (31625010,U1505224, and J1310027 to D.Z.; 81422018, U1405225, and 81372617 to L.C.; 81472229 to L.H.), the National Basic Research Program (973) of China (2015CB910502 to L.C.), the Fundamental Research Funds for the Central Universities of China-Xiamen University (20720140551 to L.C. and 2013121034 and 20720140537 to D.Z.)

Hippo信号通路通过调控Skp2活性从而抑制细胞多倍体产生及肝癌发生

文章简介在这项研究中,课题组揭示了Hippo信号通路在限制肝脏细胞的染色体由两倍体向多倍/非整倍体转变过程中起关键作用,该机制异常将导致基因组不稳定继而诱发肝癌的发生发展。课题组通过对Hippo信号通路重要成员(WW45,Mst1/2,Lats1/2)肝脏特异性敲除和过表达国家自然科学基金委;;国家重点基础研究发展计划(973)项目;;青年千人计划;;中央高校基本科研基金的资

Rôle de la micelle de caséine sur la dénaturation thermique des solutions de protéines de lactosérum et les mécanismes d'encrassement

The present work is a contribution to better understand the influence of casein micelles on the fouling of serum whey protein solutions. In particular, experimental and numerical approaches have been carried out, at laboratory and pilot scales, to describe denaturation phenomena and better understand the role of calcium in fouling mechanisms. First of all, the effect of casein/whey mass ratio on the whey protein fouling performance was investigated in a pilot-scale PHE. The total fouling deposit mass drop significantly with the addition of casein, resulting in a minimum value located at Casein/WPI of 0.2. Exceeding this critical ratio, fouling deposit increased with elevated casein concentrations. The deposit mass drop (Casein/WPI ≤ 0.2) is unlikely to be linked to the thermal denaturation of BLG and is more probably due to the change in mineral interactions introduced by casein. The increased fouling mass (Casein/WPI ≥ 0.2) was attributed to a co-precipitation of BLG-casein complex that enhances the fouling. It is proposed that micellar casein change deeply the calcium balance and the content of CaP nanocluster modifies sharply the interactions which occur between protein species (BLG, caseins) and mineral elements (ionic calcium, Ca-P) thereby affecting the protein denaturation and fouling behavior. A novel kinetic model concerning thermal unfolding and aggregation of BLG was established. This model interprets mathematically the break-slope behavior in the Arrhenius plot and provides detailed thermodynamic information for both unfolding and aggregation processes. Based on this model, it was confirmed that ionic calcium has a protective role on the thermal unfolding of BLG at low temperature. In contrast, at higher temperatures, calcium promotes aggregation and the formation of unfolded BLG species. A bench-scale fouling rig was built to perform whey protein fouling experiments in a laminar regime. A realistic 3D CFD model was achieved to simulate both the bulk and surface reactions. Results showed a linear relationship between the deposition pre-exponential factor and calcium concentration, suggesting the fouling is built in such a pattern that only one calcium ion per BLG molecule is involved. Calcium was confirmed to be essential to fouling growth with significant effects both on the thermal denaturation and deposition processes. Finally, the effect of casein/whey ratio on the whey protein fouling was investigated in the laboratory-scale fouling device. Results revealed a similar effect of casein on fouling mitigation as those found in the pilot plant. However, in this case, the fouling was suppressed and maintained at a low extent even at high Casein/WPI ratios (up to 4). The presence of individual caseins in the serum phase was considered to be responsible for this fouling mitigation probably through their chaperon-like activities. However, when the pH of the fouling solution is set at 6.6, casein is shown to lose its fouling-mitigating effect at higher ratios. This behavior is related to its weak ability of casein micelle to control ionic calcium in the serum phase at lower pH, resulting in higher calcium concentration facilitating BLG denaturation and deposition accumulation. A lower amount of dissociated caseins in the serum phase at pH 6.6 could also explain the increase in fouling mass because they are not in sufficient concentration to perform chaperone-like functions.Le présent travail est une contribution pour mieux comprendre l’influence des micelles de caseine sur l’encrassement de solutions de protéines sériques. En particulier, des approches expérimentales et numériques ont été réalisées, à des tailles laboratoires et pilotes, pour décrire les phénomènes de dénaturation et mieux cerner le rôle du calcium dans les mécanismes d’encrassement. Tout d'abord, l'effet du ratio massique caséine / lactosérum sur les performances d'encrassement des protéines de lactosérum a été étudié dans un échangeur à Plaques à l'échelle pilote. La masse totale du dépôt d'encrassement chute d’abord de manière significative avec l'augmentation de la concentration en caséine, atteignant un minimum quand le ratio vaut 0,2. Au-delà de cette valeur, la masse de dépôt réaugmente. La chute de la masse du dépôt, pour un ratio ≤ 0,2, ne semble pas être corrélée à la dénaturation thermique du BLG mais plus probablement due à la modification des interactions minérales introduites par la caséine. L'augmentation de la masse de dépôt, pour un ratio ≥ 0,2, semble être liée à une co-précipitation du complexe BLG-caséine qui augmente l'encrassement. Il est suggéré que la présence de caséine micellaire modifie profondément l'équilibre calcique en solution et que la teneur en nanocluster de Ca-P modifie fortement les interactions entre les espèces protéiques et les minéraux (calcium ionique, Ca-P) affectant ainsi la dénaturation des protéines et la précipitation des minéraux. Un nouveau modèle cinétique concernant le dépliement thermique et l'agrégation de BLG a été établi. Ce modèle est en mesure de justifier la rupture de pente dans le diagramme d'Arrhenius et de fournir des informations thermodynamiques détaillées pour les processus de dépliement et d'agrégation. Sur la base de ce modèle, il a été confirmé que le calcium ionique avait un rôle protecteur sur le dépliement thermique du BLG à basse température. En revanche, à des températures plus élevées, le calcium favorise l'agrégation et la formation d'espèces BLG dépliées. Un dispositif d'encrassement à l'échelle laboratoire a été construit et tester avec des protéines de lactosérum en régime laminaire. Un modèle CFD 3D réaliste a été implémenté simulant à la fois les réactions au cœur du fluide et en surface. Les résultats ont montré une relation linéaire entre le facteur pré-exponentiel et la concentration de calcium, ce qui suggère que l'encrassement nécessite qu’une seule molécule de calcium soit associée à une protéine de BLG. Il est confirmé que le calcium est essentiel à l'encrassement avec des effets significatifs à la fois sur les processus de dénaturation thermique et sur la croissance du dépôt. Enfin, l'effet du ratio caséine / lactosérum sur l'encrassement a été étudié avec un dispositif d'encrassement de laboratoire. Les résultats laboratoires montrent que la caséine réduit l’aptitude à l’encrassement comme déterminé précédemment avec l’installation pilote. Cependant, dans ce cas, l'encrassement reste à un niveau faible y compris pour des ratios élevés (jusqu'à 4). La présence de caséines individuelles dans la phase sérique a été considérée comme responsable de cette atténuation de l'encrassement, probablement par leurs activités de type chaperon. Cependant, quand le pH de la solution d'encrassement est fixé à 6,6, il est démontré que la caséine perd son effet d'atténuation de l'encrassement pour des ratios plus élevés. Ce comportement est lié à sa faible capacité de micelle de caséine à contrôler le calcium ionique dans la phase sérique à un pH plus bas, entraînant une concentration plus élevée en calcium facilitant la dénaturation de la BLG et l'accumulation de dépôts. Une quantité plus faible de caséines dissociées dans la phase sérique à pH 6,6 pourrait aussi expliquer l'augmentation de la masse d'encrassement car elles ne sont pas en concentration suffisantes pour remplir des fonctions de type chaperon

Role of casein micelle on the thermal denaturation of whey protein solutions and fouling mechanisms

Le présent travail est une contribution pour mieux comprendre l’influence des micelles de caseine sur l’encrassement de solutions de protéines sériques. En particulier, des approches expérimentales et numériques ont été réalisées, à des tailles laboratoires et pilotes, pour décrire les phénomènes de dénaturation et mieux cerner le rôle du calcium dans les mécanismes d’encrassement. Tout d'abord, l'effet du ratio massique caséine / lactosérum sur les performances d'encrassement des protéines de lactosérum a été étudié dans un échangeur à Plaques à l'échelle pilote. La masse totale du dépôt d'encrassement chute d’abord de manière significative avec l'augmentation de la concentration en caséine, atteignant un minimum quand le ratio vaut 0,2. Au-delà de cette valeur, la masse de dépôt réaugmente. La chute de la masse du dépôt, pour un ratio ≤ 0,2, ne semble pas être corrélée à la dénaturation thermique du BLG mais plus probablement due à la modification des interactions minérales introduites par la caséine. L'augmentation de la masse de dépôt, pour un ratio ≥ 0,2, semble être liée à une co-précipitation du complexe BLG-caséine qui augmente l'encrassement. Il est suggéré que la présence de caséine micellaire modifie profondément l'équilibre calcique en solution et que la teneur en nanocluster de Ca-P modifie fortement les interactions entre les espèces protéiques et les minéraux (calcium ionique, Ca-P) affectant ainsi la dénaturation des protéines et la précipitation des minéraux. Un nouveau modèle cinétique concernant le dépliement thermique et l'agrégation de BLG a été établi. Ce modèle est en mesure de justifier la rupture de pente dans le diagramme d'Arrhenius et de fournir des informations thermodynamiques détaillées pour les processus de dépliement et d'agrégation. Sur la base de ce modèle, il a été confirmé que le calcium ionique avait un rôle protecteur sur le dépliement thermique du BLG à basse température. En revanche, à des températures plus élevées, le calcium favorise l'agrégation et la formation d'espèces BLG dépliées. Un dispositif d'encrassement à l'échelle laboratoire a été construit et tester avec des protéines de lactosérum en régime laminaire. Un modèle CFD 3D réaliste a été implémenté simulant à la fois les réactions au cœur du fluide et en surface. Les résultats ont montré une relation linéaire entre le facteur pré-exponentiel et la concentration de calcium, ce qui suggère que l'encrassement nécessite qu’une seule molécule de calcium soit associée à une protéine de BLG. Il est confirmé que le calcium est essentiel à l'encrassement avec des effets significatifs à la fois sur les processus de dénaturation thermique et sur la croissance du dépôt. Enfin, l'effet du ratio caséine / lactosérum sur l'encrassement a été étudié avec un dispositif d'encrassement de laboratoire. Les résultats laboratoires montrent que la caséine réduit l’aptitude à l’encrassement comme déterminé précédemment avec l’installation pilote. Cependant, dans ce cas, l'encrassement reste à un niveau faible y compris pour des ratios élevés (jusqu'à 4). La présence de caséines individuelles dans la phase sérique a été considérée comme responsable de cette atténuation de l'encrassement, probablement par leurs activités de type chaperon. Cependant, quand le pH de la solution d'encrassement est fixé à 6,6, il est démontré que la caséine perd son effet d'atténuation de l'encrassement pour des ratios plus élevés. Ce comportement est lié à sa faible capacité de micelle de caséine à contrôler le calcium ionique dans la phase sérique à un pH plus bas, entraînant une concentration plus élevée en calcium facilitant la dénaturation de la BLG et l'accumulation de dépôts. Une quantité plus faible de caséines dissociées dans la phase sérique à pH 6,6 pourrait aussi expliquer l'augmentation de la masse d'encrassement car elles ne sont pas en concentration suffisantes pour remplir des fonctions de type chaperon.The present work is a contribution to better understand the influence of casein micelles on the fouling of serum whey protein solutions. In particular, experimental and numerical approaches have been carried out, at laboratory and pilot scales, to describe denaturation phenomena and better understand the role of calcium in fouling mechanisms. First of all, the effect of casein/whey mass ratio on the whey protein fouling performance was investigated in a pilot-scale PHE. The total fouling deposit mass drop significantly with the addition of casein, resulting in a minimum value located at Casein/WPI of 0.2. Exceeding this critical ratio, fouling deposit increased with elevated casein concentrations. The deposit mass drop (Casein/WPI ≤ 0.2) is unlikely to be linked to the thermal denaturation of BLG and is more probably due to the change in mineral interactions introduced by casein. The increased fouling mass (Casein/WPI ≥ 0.2) was attributed to a co-precipitation of BLG-casein complex that enhances the fouling. It is proposed that micellar casein change deeply the calcium balance and the content of CaP nanocluster modifies sharply the interactions which occur between protein species (BLG, caseins) and mineral elements (ionic calcium, Ca-P) thereby affecting the protein denaturation and fouling behavior. A novel kinetic model concerning thermal unfolding and aggregation of BLG was established. This model interprets mathematically the break-slope behavior in the Arrhenius plot and provides detailed thermodynamic information for both unfolding and aggregation processes. Based on this model, it was confirmed that ionic calcium has a protective role on the thermal unfolding of BLG at low temperature. In contrast, at higher temperatures, calcium promotes aggregation and the formation of unfolded BLG species. A bench-scale fouling rig was built to perform whey protein fouling experiments in a laminar regime. A realistic 3D CFD model was achieved to simulate both the bulk and surface reactions. Results showed a linear relationship between the deposition pre-exponential factor and calcium concentration, suggesting the fouling is built in such a pattern that only one calcium ion per BLG molecule is involved. Calcium was confirmed to be essential to fouling growth with significant effects both on the thermal denaturation and deposition processes. Finally, the effect of casein/whey ratio on the whey protein fouling was investigated in the laboratory-scale fouling device. Results revealed a similar effect of casein on fouling mitigation as those found in the pilot plant. However, in this case, the fouling was suppressed and maintained at a low extent even at high Casein/WPI ratios (up to 4). The presence of individual caseins in the serum phase was considered to be responsible for this fouling mitigation probably through their chaperon-like activities. However, when the pH of the fouling solution is set at 6.6, casein is shown to lose its fouling-mitigating effect at higher ratios. This behavior is related to its weak ability of casein micelle to control ionic calcium in the serum phase at lower pH, resulting in higher calcium concentration facilitating BLG denaturation and deposition accumulation. A lower amount of dissociated caseins in the serum phase at pH 6.6 could also explain the increase in fouling mass because they are not in sufficient concentration to perform chaperone-like functions

Improved Calculation of Load and Resistance Factors Based on Third-Moment Method

Load and resistance factor design (LRFD) is widely used in building codes for reliability design. In the calculation of load and resistance factors, the third-moment method (3M) has been proposed to overcome the shortcomings (e.g., inevitable iterative computation, requirement of probability density functions (PDFs) of random variables) of other methods. With the existing 3M method, the iterative is simplified to one computation, and the PDFs of random variables are not required. In this paper, the computation of load and resistance factors is further simplified to no iterations. Furthermore, the accuracy of the proposed method is proved to be higher than the existing 3M methods. Additionally, with the proposed method, the limitations regarding applicable range in the existing 3M methods are avoided. With several examples, the comparison of the existing 3M method, the ASCE method, the Mori method, and the proposed method is given. The results show that the proposed method is accurate, simple, safe, and saves material

Experimental Study on the Difference of Shale Mechanical Properties

This paper studies the anisotropic characteristics of shale and the difference in mechanical performance between deep shale and outcrop shale. The outcrop shale was collected from the Shuanghe section in Changning County, southern Sichuan, and the deep shale was collected from the Wells Yi201 and Lu202. Study their basic mechanical parameters, failure modes, and wave velocity responses through laboratory tests. Research shows that with the increase of bedding angle, the deformation mode has the trend from elastic deformation to plastic deformation in high-stress state. When the bedding angles are 0°, 30°, and 45°, the weak bedding surface plays a leading role in the formation of the failure surface trend. As the bedding angle increases to 60° and 90°, its influence is weakened. The tensile strength, elastic modulus, and wave velocity decrease with the increase of bedding angle. The compressive strength and Poisson’s ratio have the law of U-type change, there are higher values at 0° and 90°, and the lowest values are at 30°. The brittleness index first increases and then decreases with the increase of the bedding angle. The tensile strength and Poisson’s ratio of outcrop shale and deep shale are close, but the compressive strength of deep shale is only 1/3 of outcrop shale, the elastic modulus is only 3/4 of outcrop shale, and the failure of deep shale is accompanied by instability failure

An Alternative Formulation of Collaborative Optimization Based on Geometric Analysis

Collaborative optimization (CO) is a multidisciplinary design optimization (MDO) method with bilevel computational structure, which decomposes the original optimization problem into one system-level problem and several subsystem problems. The strategy of decomposition in CO is a useful way for solving large engineering design problems. However, the computational difficulties caused by the system-level consistency equality constraints hinder the development of CO. In this paper, an alternative formulation of CO called CO with combination of linear approximations (CLA-CO) is presented based on the geometric analysis of CO, which is more intuitive and direct than the previous algebraic analysis. In CLA-CO, the consistency equality constraints in CO are replaced by linear approximations to the subsystem responses. As the iterative process goes on, more linear approximations are added into the system level. Consequently, the combination of these linear approximations makes the system-level problem gradually approximate the original problem. In CLA-CO, the advantages of the decomposition strategy are maintained while the computational difficulties of the conventional CO are avoided. However, there are still difficulties in applying the presented CLA-CO to problems with nonconvex constraints. The application of CLA-CO to three optimization problems, a numerical test problem, a composite beam design problem, and a gear reducer design problem, illustrates the capabilities and limitations of CLA-CO

Numerical simulation study of rock breaking mechanism by high voltage electric pulse

High-voltage electric pulse(HVEP)drilling has become a new and efficient rock breaking method, which is also the research focus in the field of drilling speed increase. To probe into rock breaking mechanism of high voltage electric pulse, this study establishes a two-dimensional numerical model of multi-physical field coupling electric breakdown of single pair of electrodes. The model reproduces the generation of plasma channels in homogeneous red sandstone from the coupling of current field, electric breakdown field and circuit field. This paper analyzes the effect of electrode pair angle, voltage and electrode spacing on rock electrical breakdown(that is, the formation of plasma channel in rock). The model includes the circuit structure parameters of pulse tool, the occurrence and development of electrical breakdown, and the relationship between electrical breakdown intensity and time. Results indicate that the plasma channel begins to sprout from the partial area near the top of the discharge electrode and develops towards the partial weak dielectric strength. With the voltage value of loading pulse increasing gradually, the time of electrical breakdown decreases gradually; comparatively, the equivalent failure volume of rock model increases gradually, and there is a positive correlation between them. On the precondition that the rock can be electrically broken, increasing the electrode spacing can improve the rock breaking efficiency of high voltage electric pulse. The equivalent failure volume of rock shows significant fluctuations during the gradual increase of electrode inclination angle of discharge electrode, and its extreme value mostly appears in the range of electrode inclination angle of 35°~ 55°. To further promote the industrial application of high-voltage electric pulse rock breaking, this paper proposes a three-dimensional numerical model of multi-physical field coupling dynamic electric breakdown of red sandstone based on two-dimensional model, reproducing the appearance of the fracture crater in the rock during the rock breaking process with electrode bit. At the same time, the self-designed coaxial electrode bit is selected for experiments of electric breakdown, and the laboratory experimental results of electric breakdown confirm the simulation experimental results