Model-based evaluation and process development of continuous chromatography

Multi-column periodic counter-current (PCC) chromatography has been proposed as continuous capturing technology to improve the process productivity and resin capacity utilization, as well as reduce buffer consumption and equipment footprint, which is applying for monoclonal antibody (mAb) capture with Protein A affinity resin. Due to the complexity of continues chromatography, some mathematical framework should be developed to aid the process development. Please click Additional Files below to see the full abstract

Investigation of Durability and Performance of High Friction Surface Treatment

The Indiana Department of Transportation (INDOT) completed a total of 25 high friction surface treatment (HFST) projects across the state in 2018. This research study attempted to investigate the durability and performance of HFST in terms of its HFST-pavement system integrity and surface friction performance. Laboratory tests were conducted to determine the physical and mechanical properties of epoxy-bauxite mortar. Field inspections were carried out to identify site conditions and common early HFST distresses. Cyclic loading test and finite element method (FEM) analysis were performed to evaluate the bonding strength between HFST and existing pavement, in particular chip seal with different pretreatments such as vacuum sweeping, shotblasting, and scarification milling. Both surface friction and texture tests were undertaken periodically (generally once every 6 months) to evaluate the surface friction performance of HFST. Crash records over a 5-year period, i.e., 3 years before installation and 2 years after installation, were examined to determine the safety performance of HFST, crash modification factor (CMF) in particular. It was found that HFST epoxy-bauxite mortar has a coefficient of thermal expansion (CTE) significantly higher than those of hot mix asphalt (HMA) mixtures and Portland cement concrete (PCC), and good cracking resistance. The most common early HFST distresses in Indiana are reflective cracking, surface wrinkling, aggregate loss, and delamination. Vacuum sweeping is the optimal method for pretreating existing pavements, chip seal in particular. Chip seal in good condition is structurally capable of providing a sound base for HFST. On two-lane highway curves, HFST is capable of reducing the total vehicle crash by 30%, injury crash by 50%, and wet weather crash by 44%, and providing a CMF of 0.584 in Indiana. Great variability may arise in the results of friction tests on horizontal curves by the use of locked wheel skid tester (LWST) due both to the nature of vehicle dynamics and to the operation of test vehicle. Texture testing, however, is capable of providing continuous texture measurements that can be used to calculate a texture height parameter, i.e., mean profile depth (MPD), not only for evaluating friction performance but also implementing quality control (QC) and quality assurance (QA) plans for HFST

xFraud: Explainable Fraud Transaction Detection

At online retail platforms, it is crucial to actively detect the risks of transactions to improve customer experience and minimize financial loss. In this work, we propose xFraud, an explainable fraud transaction prediction framework which is mainly composed of a detector and an explainer. The xFraud detector can effectively and efficiently predict the legitimacy of incoming transactions. Specifically, it utilizes a heterogeneous graph neural network to learn expressive representations from the informative heterogeneously typed entities in the transaction logs. The explainer in xFraud can generate meaningful and human-understandable explanations from graphs to facilitate further processes in the business unit. In our experiments with xFraud on real transaction networks with up to 1.1 billion nodes and 3.7 billion edges, xFraud is able to outperform various baseline models in many evaluation metrics while remaining scalable in distributed settings. In addition, we show that xFraud explainer can generate reasonable explanations to significantly assist the business analysis via both quantitative and qualitative evaluations.Comment: This is the extended version of a full paper to appear in PVLDB 15 (3) (VLDB 2022

Numerical simulation on the aerodynamic performance of the high-speed train under crosswinds

With the continuously increased speed of the high-speed train, the lateral aerodynamic performance of high-speed trains has attracted more and more attention. Under strong crosswinds, the aerodynamic performance of trains deteriorate and air drag, lift and lateral forces borne by trains quickly increase, which has an impact on the lateral stability of trains and even leads to train derailment. This paper adopted computational fluid dynamics theory to establish an aerodynamic model for a high-speed train, computed aerodynamic forces and moments acting on the high-speed train and obtained the unsteady flow field of the high-speed train. In the meanwhile, this paper combined with multi-body system dynamics theory to establish a system dynamics model for the train and analyzed the safe aerodynamic performance of the high-speed train under cross winds. Computational results showed: Under cross winds, the aerodynamic performance of the high-speed train had a random fluctuation. When wind direction angle was 90°, aerodynamic forces (drag, lift and lateral forces) and moments (overturning moment, shaking moment and nodding moment) borne by the high-speed train were the largest; train speed was a main factor affecting the size of positive pressures of train and cross wind velocity had no obvious impacts on the positive and negative pressures of train body; the aerodynamic forces and moments of the high-speed train had a random fluctuation within a certain range with time; the frequency for the peak value of power spectral density of lateral forces of head train was within 25 Hz and the peak value of power spectral density was the largest when the main frequency was 1.6 Hz; the frequency for the peak value of power spectral density of overturning moment of head train was within 20 Hz and main frequency was 0.57 Hz. When the cross wind speed was 15 m/s, all safety indexes of the high-speed train running at the speed of 250 km/h were within the range of limited values and satisfied design requirements. Aerodynamic performance of the high-speed train with the suction chamber under the cross wind was computed and compared with original results. Aerodynamic force and force moments of the high-speed train under cross wind will be reduced obviously and running safety of the high-speed train can be improved through application of the suction chamber

Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes

Thy-1 Attenuates TNF-α-Activated Gene Expression in Mouse Embryonic Fibroblasts via Src Family Kinase

Heterogeneous surface expression of Thy-1 in fibroblasts modulates inflammation and may thereby modulate injury and repair. As a paradigm, patients with idiopathic pulmonary fibrosis, a disease with pathologic features of chronic inflammation, demonstrate an absence of Thy-1 immunoreactivity within areas of fibrotic activity (fibroblast foci) in contrast to the predominant Thy-1 expressing fibroblasts in the normal lung. Likewise, Thy-1 deficient mice display more severe lung fibrosis in response to an inflammatory injury than wildtype littermates. We investigated the role of Thy-1 in the response of fibroblasts to the pro-inflammatory cytokine TNF-α. Our study demonstrates distinct profiles of TNF-α-activated gene expression in Thy-1 positive (Thy-1+) and negative (Thy-1−) subsets of mouse embryonic fibroblasts (MEF). TNF-α induced a robust activation of MMP-9, ICAM-1, and the IL-8 promoter driven reporter in Thy-1− MEFs, in contrast to only a modest increase in Thy-1+ counterparts. Consistently, ectopic expression of Thy-1 in Thy-1− MEFs significantly attenuated TNF-α-activated gene expression. Mechanistically, TNF-α activated Src family kinase (SFK) only in Thy-1− MEFs. Blockade of SFK activation abrogated TNF-α-activated gene expression in Thy-1− MEFs, whereas restoration of SFK activation rescued the TNF-α response in Thy-1+ MEFs. Our findings suggest that Thy-1 down-regulates TNF-α-activated gene expression via interfering with SFK- and NF-κB-mediated transactivation. The current study provides a novel mechanistic insight to the distinct roles of fibroblast Thy-1 subsets in inflammation

Simulating liquid-vapor phase separation under shear with lattice Boltzmann method

We study liquid-vapor phase separation under shear via the Shan-Chen lattice Boltzmann model. Besides the rheological characteristics, we analyze the Kelvin-Helmholtz(K-H) instability resulting from the tangential velocity difference of the fluids on two sides of the interface. We discuss also the growth behavior of droplets. The domains being close to the walls are lamellar-ordered, where the hydrodynamic effects dominate. The patterns in the bulk of the system are nearly isotropic, where the domain growth results mainly from the diffusion mechanism. Both the interfacial tension and the K-H instability make the liquid-bands near the walls tend to rupture. When the shear rate increases, the inequivalence of evaporation in the upstream and coagulation in the downstream of the flow as well as the role of surface tension makes the droplets elongate obliquely. Stronger convection makes easier the transferring of material particles so that droplets become larger.Comment: Science in China (Series G) (in press

Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease–related blood-based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group

Introduction: Pre-analytical sample handling might affect the results of Alzheimer's disease blood-based biomarkers. We empirically tested variations of common blood collection and handling procedures. Methods: We created sample sets that address the effect of blood collection tube type, and of ethylene diamine tetraacetic acid plasma delayed centrifugation, centrifugation temperature, aliquot volume, delayed storage, and freeze–thawing. We measured amyloid beta (Aβ)42 and 40 peptides with six assays, and Aβ oligomerization-tendency (OAβ), amyloid precursor protein (APP)699-711, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), total tau (t-tau), and phosphorylated tau181. Results: Collection tube type resulted in different values of all assessed markers. Delayed plasma centrifugation and storage affected Aβ and t-tau; t-tau was additionally affected by centrifugation temperature. The other markers were resistant to handling variations. Discussion: We constructed a standardized operating procedure for plasma handling, to facilitate introduction of blood-based biomarkers into the research and clinical settings