Tuning Co valence state in cobalt oxyhydrate superconductor by post reduction

We report a successful tuning of Co valence state in cobalt oxyhydrate superconductor via a facile post reduction using NaOH as reducing agent. The change in Co valence was precisely determined by measuring the volume of the released oxygen. The possible hydronium-incorporation was greatly suppressed in concentrated NaOH solution, making the absolute Co valence determinable. As a result, an updated superconducting phase diagram was obtained, which shows that the superconducting transition temperature increases monotonically with increasing Co valence in a narrow range from +3.58 to +3.65.Comment: 17 pages, 5 figures and 1 table. Chem. Mat. in pres

SeqRate: sequence-based protein folding type classification and rates prediction

Protein folding rate is an important property of a protein. Predicting protein folding rate is useful for understanding protein folding process and guiding protein design. Most previous methods of predicting protein folding rate require the tertiary structure of a protein as an input. And most methods do not distinguish the different kinetic nature (two-state folding or multi-state folding) of the proteins. Here we developed a method, SeqRate, to predict both protein folding kinetic type (two-state versus multi-state) and real-value folding rate using sequence length, amino acid composition, contact order, contact number, and secondary structure information predicted from only protein sequence with support vector machines.We systematically studied the contributions of individual features to folding rate prediction. On a standard benchmark dataset, the accuracy of folding kinetic type classification is 80%. The Pearson correlation coefficient and the mean absolute difference between predicted and experimental folding rates (sec-1) in the base-10 logarithmic scale are 0.81 and 0.79 for two-state protein folders, and 0.80 and 0.68 for three-state protein folders. SeqRate is the first sequence-based method for protein folding type classification and its accuracy of fold rate prediction is improved over previous sequence-based methods. Its performance can be further enhanced with additional information, such as structure-based geometric contacts, as inputs.Both the web server and software of predicting folding rate are publicly available at http://casp.rnet.missouri.edu/fold_rate/index.html

Valley vortex states and degeneracy lifting via photonic higher-band excitation

We demonstrate valley-dependent vortex generation in a photonic graphene. Without breaking the inversion symmetry, excitation of two equivalent valleys leads to formation of an optical vortex upon Bragg-reflection to the third valley, with its chirality determined by the valley degree of freedom. Vortex-antivortex pairs with valley-dependent topological charge flipping are also observed and corroborated by numerical simulations. Furthermore, we develop a three-band effective Hamiltonian model to describe the dynamics of the coupled valleys, and find that the commonly used two-band model is not sufficient to explain the observed vortex degeneracy lifting. Such valley-polarized vortex states arise from high-band excitation without inversion symmetry breaking or synthetic-field-induced gap opening. Our results from a photonic setting may provide insight for the study of valley contrasting and Berry-phase mediated topological phenomena in other systems

A Separated-Flow Model for 2-D Viscous Flows around Bluff Bodies Using the Panel Method

Panel methods have been applied to many fields of fluid owing to their computational efficiency. However, their applications are limited in simulating highly turbulent flow with separations due to the inviscid flow assumptions, such as those associated with train aerodynamics. Some researchers employed the wake models to simulate large vortices in the wake of trains with predetermined separation locations according to experimental results. In this paper, a modified 2-D constant source/vortex panel method for modelling the separated flow around 2-D bluff bodies is presented. The proposed separated-flow model includes the prediction of separation locations based on the integral boundary-layer method and the shear layer, and large vortices in the wake of the bluff bodies are modelled by the wake model. The proposed method is validated by comparing the calculated pressure distribution on a 2-D circular cylinder with the experimental results. The method is then applied to simulate the flow around a 2-D generic train and calculate the pressure distribution on the train. Since trains run very close to the ground, the effect of the ground configuration on the pressure distribution of the 2-D train is also investigated in this paper using the proposed method. The main contribution of the work is to present a 2-D separated-flow model with wake modelling and separation prediction. The proposed model can be used in the rapid evaluation of bluff-body aerodynamics

Study on the Time-lag Failure of Sandstone With Different Degrees of Unloading Damage

The unloading effect of rock mass excavation is an inevitable practice, and it’s often characterized by a relatively large-scale engineering hazard with a noticeable time lag.A set of unloading triaxial tests were conducted on a sandstone rock to establish the deformation law and the threshold time. Based on the renormalization group theory, the unloading sandstone model was developed by considering the interaction between particles. Similarly, a logistic model was used to predict the unloading damage of sandstone. The unloading time lag damage of sandstone rock was predicted by using the damage threshold. The research shows that: (1) The higher the degree of unloading, the shorter the time-lag failure. (2) The damage range of critical values was optimized. (3) The error between the predicted value and the experimental value of the time threshold was almost less than 5 %, the prediction result was found to be good, and the employed logistic evolution model was reasonable. The findings of this research provide a prediction method and precise information about the mechanism of unloading time lag deformation. Therefore, it can be used as a reference for excavation-support design of underground structures

Integration of upstream and downstream for a hybrid continuous process development and manufacturing for a stable monoclonal antibody produced in CHO cell culture

Process intensification by continuous operation has been successfully applied in the chemical industry, when batch processes matured several decades ago. Fully integrated upstream and downstream continuous processing has also shown great potential for increased productivity and reduced cost in biomanufacturing using mammalian cell culture. After a few decades of development, continuous or perfusion cell culture has demonstrated for manufacturing of labile proteins or low-titer processes. Due to significant challenges implementing fully integrated continuous biomanufacturing and the fact that fed-batch cell culture has not yet matured, fed-batch cell culture and batch chromatography steps are still predominant for stable protein manufacturing in the industry. In comparison to perfusion cell culture, continuous or semi-continuous downstream processing for stable monoclonal antibodies (mAbs) has developed within less than a decade. Due to a high titer, e.g., 8-10 g/L, already achieved via fed-batch cell culture, which challenges the processing capacity for batch downstream commercial manufacturing, the demand of continuous chromatography operation dramatically increases. Here, we present a case study developing a hybrid continuous upstream and downstream as our next generation process for production of a stable mAb. For upstream, we implemented N-1 perfusion seed, which significantly increased the seeding density for fed-batch production. After media and process parameter optimization, the product titer for the intensified fed-batch process with high-seed increased more than 100% over the original fed-batch process. It should be noted that the original fed-batch process was optimized and used for clinical manufacturing at 1000-L scale. For next generation downstream, we developed multi-column chromatography for Protein A step, automated VI step and integrated pool-less polishing chromatography steps with increased productivity and reduction in resin requirement, buffer consumption and processing time. The next generation process with perfusion N-1 seed and continuous chromatography steps has been scaled up in 500-L bioreactor, and now has been demonstrated for full implementation in a GMP manufacturing facility at the 2000-L scale. We will present full set of data to compare the original optimized batch process at 1000-L scale and the next generation process at 2000-L scale for the stable mAb production using CHO cell culture. We believe that the hybrid continuous process is relatively easy to develop and implement in GMP manufacturing with significantly higher productivity than conventional fed-batch process for now, while the hybrid continuous process lays a good foundation for us to further develop and implement fully continuous upstream and downstream process in manufacturing with even higher productivity in future

Next generation perfusion process development for production of biologics

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Subcellular localization and function study of a secreted phospholipase C from Nocardia seriolae

Fish nocardiosis is a chronic systemic granulomatous disease, andNocardia seriolaeis the main pathogen that causes this disease. But the pathogenesis and virulence factors ofN. seriolaeare not fully understood. A phospholipase C (PLC), which was likely to be a secreted protein targeting host cell mitochondria, was found by the bioinformatics analysis on the whole genome sequence ofN. seriolae. In order to determine the subcellular localization and study the preliminary function of PLC fromN. seriolae(NsPLC), the gene cloning, secreted protein identification, subcellular localization in host cells and apoptosis detection of NsPLC were carried out in this study. The results showed that NsPLC was a secreted protein by mass spectrometry analysis of extracellular products fromN. seriolae. Subcellular localization of NsPLC-GFP fusion protein in FHM cells revealed that the green fluorescence exhibited a punctate distribution near the nucleus and did not co-localize with mitochondria. In addition, apoptosis assay suggested that apoptosis was induced in FHM cells by the overexpression of NsPLC. This study may lay the foundation for further study on the function of NsPLC and promote the understanding of the virulence factors and pathogenic mechanism ofN. seriolae

Specific fungi associated with response to capsulized fecal microbiota transplantation in patients with active ulcerative colitis

ObjectiveFecal microbiota transplantation (FMT) is a novel microbial treatment for patients with ulcerative colitis (UC). In this study, we performed a clinical trial of capsulized FMT in UC patients to determine the association between the gut fungal community and capsulized FMT outcomes.DesignThis study recruited patients with active UC (N = 22) and healthy individuals (donor, N = 9) according to the criteria. The patients received capsulized FMT three times a week. Patient stool samples were collected before (week 0) and after FMT follow-up visits at weeks 1, 4, and 12. Fungal communities were analysed using shotgun metagenomic sequencing.ResultsAccording to metagenomic analysis, fungal community evenness index was greater in samples collected from patients, and the overall fungal community was clustered among the samples collected from donors. The dominant fungi in fecal samples collected from donors and patients were Ascomycota and Basidiomycota. However, capsulized FMT ameliorated microbial fungal diversity and altered fungal composition, based on metagenomic analysis of fecal samples collected before and during follow-up visits after capsulized FMT. Fungal diversity decreased in samples collected from patients who achieved remission after capsulized FMT, similar to samples collected from donors. Patients achieving remission after capsulized FMT had specific enrichment of Kazachstania naganishii, Pyricularia grisea, Lachancea thermotolerans, and Schizosaccharomyces pombe compared with patients who did not achieve remission. In addition, the relative abundance of P. grisea was higher in remission fecal samples during the follow-up visit. Meanwhile, decreased levels of pathobionts, such as Candida and Debaryomyces hansenii, were associated with remission in patients receiving capsulized FMT.ConclusionIn the metagenomic analysis of fecal samples from donors and patients with UC receiving capsulized FMT, shifts in gut fungal diversity and composition were associated with capsulized FMT and validated in patients with active UC. We also identified the specific fungi associated with the induction of remission. ClinicalTrails.gov (NCT03426683)