The working capability of multi-stage pumps, such as electrical submersible pumps (ESPs) handling multiphase flow, has always been a big challenge for petroleum industries. The major problem is ...associated with the agglomeration of gas bubbles inside ESP-impellers, causing pump performance degradation ranging from mild to severe deterioration (surging/gas pockets). Previous literature showed that the two-phase performance of ESPs is greatly affected by gas involvement, rotational speed, bubble size, and fluid viscosity. Thus, it is necessary to understand which parameter is actually accountable for performance degradation and different flow patterns in ESP, and how it can be controlled. The present study is mainly focused on (1) the main parameters that impede two-phase performance of different ESPs; (2) comparison of existing empirical models (established for two-phase performance prediction and surging initiation) with our single-stage centrifugal pump results to determine their validity and working-range; (3) gas-handling techniques applied to enhance the multiphase performance of ESPs. Firstly, it aims at understanding the internal flow mechanism in different ESP designs, followed by test studies based on empirical models, visualization techniques, bubble-size measurements, and viscosity analysis. The CFD-based (computational fluid dynamics) numerical analysis concerning multiphase flow is described as well. Furthermore, gas-handling design methods are discussed that are helpful in developing the petroleum industry by enhancing the multiphase performance of ESPs.
Clinical deployment of oligonucleotides requires delivery technologies that improve stability, target tissue accumulation and cellular internalization. Exosomes show potential as ideal delivery ...vehicles. However, an affordable generalizable system for efficient loading of oligonucleotides on exosomes remain lacking. Here, we identified an Exosomal Anchor DNA Aptamer (EAA) via SELEX against exosomes immobilized with our proprietary CP05 peptides. EAA shows high binding affinity to different exosomes and enables efficient loading of nucleic acid drugs on exosomes. Serum stability of thrombin inhibitor NU172 was prolonged by exosome-loading, resulting in increased blood flow after injury in vivo. Importantly, Duchenne Muscular Dystrophy PMO can be readily loaded on exosomes via EAA (EXO
EAA-PMO
). EXO
EAA-PMO
elicited significantly greater muscle cell uptake, tissue accumulation and dystrophin expression than PMO in vitro and in vivo. Systemic administration of EXO
EAA-PMO
elicited therapeutic levels of dystrophin restoration and functional improvements in
mdx
mice. Altogether, our study demonstrates that EAA enables efficient loading of different nucleic acid drugs on exosomes, thus providing an easy and generalizable strategy for loading nucleic acid therapeutics on exosomes.
Synopsis
This study identifies an exosome-binding DNA aptamer (Exosomal Anchor Aptamer—EAA) and demonstrates that EAA binds to exosomes of different origins effectively and enables efficient loading of different nucleic acid drugs on exosomes. This study provides an easy generalizable strategy for loading nucleic acid therapeutics on exosomes orthogonal to CD63-binding peptides, which are better suited for protein and peptide loading.
EAA showed high binding affinity to exosomes irrespective of origin.
EAA enabled loading of different nucleic acid drugs on exosomes, with thrombin DNA aptamer inhibitor NU172 loaded on exosomes extended the serum stability.
Duchenne Muscular Dystrophy (DMD) phosphorodiamidate morpholino oligomers (PMOs) were efficiently loaded on exosomes via EAA to form EXO
EAA-PMO
and systemic administration EXO
EAA-PMO
at low doses improved muscle function and pathologies in dystrophic mice.
This study identifies an exosome-binding DNA aptamer (Exosomal Anchor Aptamer - EAA) and demonstrates that EAA binds to exosomes of different origins effectively and enables efficient loading of different nucleic acid drugs on exosomes. This study provides an easy generalizable strategy for loading nucleic acid therapeutics on exosomes orthogonal to CD63-binding peptides, which are better suited for protein and peptide loading.
Tumor-targeting peptides have profound clinical implications in early detection and delineation of microscopic lesions for surgical resection, and also delivery of therapeutics with reduced systemic ...toxicity. Here, we demonstrate that a peptide (RS), evolved from a previously reported hepatocellular carcinoma (HCC)-targeting peptide P47, enables improved HCC micrometastasis discrimination and delineation from noncancerous tissues in murine orthotopic mice and patient biopsies, with up to 21-fold contrast. Importantly, RS targets non-small cell lung (NSCLC) and colon cancers in mice and patient biopsies, with higher selectivity for highly proliferative tumor nodules. Moreover, RS localizes to cell nucleoli of HCC, NSCLC, breast, colon and cervical cancer cells and induces nucleolar stress when conjugated with chemotherapeutic Oxaliplatin (OXA) (RS-OXA), demonstrating both cellular and subcellular targeting. RS-delivered OXA elicits significant tumor retardation in orthotopic HCC mice with markedly reduced systemic toxicity compared to OXA alone. Injection of fluorescence-labeled RS enables dynamic visualization of tumor growth in RS-OXA-treated subcutaneous HCC mice. Our study demonstrates that RS targets a spectrum of tumors and localizes to cell nucleolus, thus enabling functional imaging and targeted delivery of OXA in HCC mice, and consequently provides a versatile tool for tumor imaging and targeted therapeutics.
Biaobiao Wang,* Xiuqing Lv,* Jingrui Huang Department of Obstetrics, Xiangya Hospital Central South University, Changsha, People's Republic of China*These authors contributed equally to this ...workCorrespondence: Jingrui Huang, Department of Obstetrics, Xiangya Hospital Central South University, 87 Xiangya Road, Changsha, 410008, People's Republic of China, Email jingruihuang@hotmail.com; huangjingrui@csu.edu.cn
In order to study the internal flow characteristics of centrifugal pumps with a split impeller under gas-liquid mixed transportation conditions, this paper conducted a steady calculation of the flow ...field in the centrifugal pump under the conditions of different inlet gas volume fractions based on the Eulerian-Eulerian heterogeneous flow model, using air and water as the working media and the Schiller Nauman model for the interphase resistance. This paper takes a low specific speed centrifugal pump as the research object, through the controlling variables, using the same pump body structure and pump body geometric parameters and setting three different arrangements of long and short blades (each plan uses the same long and short blades) to explore the influence of the short blade arrangement on the low specific speed centrifugal pump performance under a gas-liquid two-phase flow. The research results show that, under pure water conditions, the reasonable arrangement of the short blade circumferential position can eliminate the hump of the centrifugal pump under low-flow conditions, can make the flow velocity in the impeller more uniform, and can optimize the performance of the pump. Under the design conditions and the gas-liquid two-phase inflow conditions, when the circumferential position of the short blades is close to the suction surface of the long blades, some of the bubbles on the suction surface of the long blade can be broken under the work of the pressure surface of the short blade and flow out of the impeller with the liquid, which improves the flow state of the flow field in the impeller.
The Hoabinhian phenomenon was long considered a late Paleolithic technocomplex in Southeast Asia. Recently, the discovery of several Hoabinhian sites in southwest China largely expanded its ...tempo-spatial distributions and enriched the toolkit of Hoabinhian hunter-gatherers. The Hoabinbian stone tools are often made with river cobbles of large to medium size and rarely reach over 150mm and 1kg. However, this perspective towards Hoabinhian cutting tools can be updated with recurring tools made on massive and even giant boulders discovered at Chinese Hoabinhian sites. Here we present the mega lithic tools (> 150mm, 2kg) from the first and also the currently known earliest Hoabinhian site – Xiaodong rockshelter in southwest China. These tools’ productional and techno-functional characteristics were described and illustrated, and whether they have utilitarian purposes was discussed. Although these massive, giant, heavy-duty Hoabinhian tools are morpho-typologically similar to those large-medium ones found at the site, their original size may endow new aspects (cognitive, technical, symbolic, social, etc.) to these tools that are still poorly understood.
Le phénomène Hoabinhian a longtemps été considéré comme un technocomplexe de la fin du Paléolithique en Asie du Sud-Est. Récemment, la découverte de plusieurs sites hoabinhiens dans le sud-ouest de la Chine a largement étendu sa distribution spatio-temporelle et enrichi l’outillage des chasseurs-cueilleurs hoabinhiens. Les outils en pierre des Hoabinhiens sont souvent fabriqués avec des galets de rivière de taille moyenne à grande et atteignent rarement plus de 150mm et 1kg. Cependant, cette approche des outils hoabinhiens peut être modifiée avec les outils réalisés sur des galets massifs, voire géants, découverts sur les sites hoabinhiens chinois. Nous présentons ici les outils lithiques de grande taille (> 150mm, 2kg) du premier site Hoabinhien, et aussi du plus ancien connu à ce jour, l’abri sous roche de Xiaodong, dans le sud-ouest de la Chine. Les caractéristiques de production et techno-fonctionnelles de ces outils ont été décrites, et la question de savoir s’ils avaient des objectifs utilitaires a été discutée. Bien que ces outils hoabinhiens massifs, géants et lourds, soient morpho-typologiquement similaires aux outils de taille moyenne et grande trouvés sur le site, leur taille originale peut leur conférer de nouveaux aspects (cognitifs, techniques, symboliques, sociaux, etc.) qui sont encore mal compris.
The radiated noise of the centrifugal pump acts as a disturbance in many applications. The radiated noise is closely related to the hydraulic design. The hydraulic parameters in the multistage pump ...are complex and the flow interaction among different stages is very strong, which in turn causes vibration and noise problems because of the strong hydraulic excitation. Hence, the mechanism of radiated noise and its relationship with hydraulics must be studied clearly. In order to find the regular pattern of the radiated noise at different operational conditions, a hybrid numerical method was proposed to obtain the flow-induced noise source based on Lighthill acoustic analogy theory, which divided the computational process into two parts: computational fluid dynamics (CFD) and computational acoustics (CA). The unsteady flow field was solved by detached eddy simulation using the commercial CFD code. The detailed flow information near the surface of the vane diffusers and the calculated flow-induced noise source was extracted as the hydraulic exciting force, both of which were used as acoustic sources for radiated noise simulation. The acoustic simulation employed the finite element method code to get the sound pressure level (SPL), frequency response, directivity, et al. results. The experiment was performed inside a semi-anechoic room with a closed type pump test rig. The pump performance and acoustic parameters of the multistage pump at different flow rates were gathered to verify the numerical methods. The computational and experimental results both reveal that the radiated noise exhibits a typical dipole characteristic behavior and its directivity varies with the flowrate. In addition, the sound pressure level (SPL) of the radiated noise fluctuates with the increment of the flow rate and the lowest SPL is generated at 0.8Qd, which corresponds to the maximum efficiency working conditions. Furthermore, the experiment detects that the sound pressure level of the radiated noise in the multistage pump rises linearly with the increase of the rotational speed. Finally, an example of a low noise pump design is processed based on the obtained noise characteristics.
The role of hot or wind pressing forming a pressure difference between the indoor and out-door of the building envelop, the unorganized infiltration air will flow into rooms. Indoor and outdoor ...temperature, outdoor wind direction and speed have an impact on the infiltration air volume. There are multiple aisles connecting the outdoor space and the station hall, leading to a large amount of outdoor air into the station. In this paper, the measurement of infiltration air volume and regional temperature in railway station was performed in Wuhan. The software ContamW was used to simulate the ventilation paths and the infiltration air volume. The changes of infiltration air volume was analyzed, and the corresponding measures to reduce the infiltration air were studied. The results showed that using air curtains with the barrier efficiency of 62.6% and closing the opening windows, the static wind and v=3 m/s of northeast wind conditions, the amount of infiltration air can be reduced by 78% and 79% separately in Wuhan area.
In this paper, a large space building model is built by CFD software to study the effect of air curtain on the reduction in infiltration air volume. The influences of the pressure difference between ...inside and outside, the air curtain air supply speed and the air curtain outlet thickness on the air curtain barrier efficiency are also discussed. The results show that when the pressure difference between indoor and outdoor is 1.0 pa, the barrier efficiency of air curtain is 40%-80% with the air curtain supply speed increasing from 8 m/s to 18 m/s. However, the barrier efficiency is 20%-45% when the indoor and outdoor pressure difference increases to 6.0 pa with the same air curtain supply speed range. At the same time, when the outdoor wind speed is 3 m/s, the rest area average temperature of the large space building with air curtain is 10.8 ºC higher than which without air curtain. The use of air curtain to reduce the amount of infiltration and improve indoor heat comfort has a very good effect.
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