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

A new sesquiterpene lactone and a new aromatic glycoside from Illicium difengpi

AbstractA new sesquiterpene lactone (1) and a new aromatic glycoside (2), together with three known compounds (3–5) were isolated from the stem bark of Illicium difengpi K. I. B et K. I. M. Their structures were determined by spectroscopic methods, including 1D and 2D NMR, HRESIMS, and chemical methods. The absolute configuration of the secondary alcohol in 1 was confirmed by Mosher's method. Compound 2 exhibited significant anti-inflammatory activity with IC50 value of 6.72μmol/L

Estimation of the cost-effective threshold of a quality-adjusted life year in China based on the value of statistical life

Cost-effective threshold (CET) is essential for health technology assessment and decision-making based on health economic evaluations. Recently, it has been argued that the commonly used once and three times of gross domestic product (GDP) per capita CETs of a quality-adjusted life year (QALY) are not necessarily empirically supported in all countries. Therefore, we aimed to estimate the CET of a QALY as times of GDP per capita in China, of which the reimbursement coverage decisions are increasingly engaging economic evaluations. Estimates on the value of statistical life (VSL) in China were identified from several studies in the literature and converted to times of GDP per capita, the weighted average of which was used for subsequent calculation. By pooling data on population mortality, health utility, and age distribution, we estimated the value of a statistical QALY (VSQ) from VSL using an established mathematical process, which represented the theoretical upper bound of CET. The corresponding point estimate and theoretical lower bound were obtained using their numerical relationships with the upper bound. Scenarios analyses were also conducted. The estimated CET, its upper bound, and its lower bound were 1.45, 2.90, and 1.16 times of GDP per capita in China, respectively. In different scenarios, the estimated CET varied but was greater than once GDP per capita in most cases. As such, the CET of a QALY in China is close to 1.5 times of GDP per capita, which should be benchmarked for future ICER-based coverage decisions

High-Throughput Sequencing of MicroRNAs in Adenovirus Type 3 Infected Human Laryngeal Epithelial Cells

Adenovirus infection can cause various illnesses depending on the infecting serotype, such as gastroenteritis, conjunctivitis, cystitis, and rash illness, but the infection mechanism is still unknown. MicroRNAs (miRNA) have been reported to play essential roles in cell proliferation, cell differentiation, and pathogenesis of human diseases including viral infections. We analyzed the miRNA expression profiles from adenovirus type 3 (AD3) infected Human laryngeal epithelial (Hep2) cells using a SOLiD deep sequencing. 492 precursor miRNAs were identified in the AD3 infected Hep2 cells, and 540 precursor miRNAs were identified in the control. A total of 44 miRNAs demonstrated high expression and 36 miRNAs showed lower expression in the AD3 infected cells than control. The biogenesis of miRNAs has been analyzed, and some of the SOLiD results were confirmed by Quantitative PCR analysis. The present studies may provide a useful clue for the biological function research into AD3 infection

Polaron Rashba effect in an asymmetric quantum dot

We study the influence of polaron Rashba effect in an asymmetric quantum dot. Using variational method, we derive the expression of the polaron ground state energy. We also discuss the dependencies of the ground state energy on the wave vector and the transverse (longitudinal) effective confinement length. It is found that the ground state energy splits into two branches due to the Rashba effect. The spin splitting energy is an increasing function of the wave vector and the Rashba SO parameter

Dendrobium nobile Lindl. Alkaloids Decreases the Level of Intracellular β-Amyloid by Improving Impaired Autolysosomal Proteolysis in APP/PS1 Mice

As the major degradation pathway for long-lived proteins and organelles, macroautophagy is a decisive factor for the survival and longevity of cells. The existing evidence indicates that the disruption of substrate proteolysis in autolysosomes is the main mechanism underlying autophagy failure in Alzheimer’s disease (AD). Thus, the restoration of normal lysosomal proteolysis and autophagy efficiency is a novel therapeutic strategy in the treatment of AD. In this study, 9-month-old APPswe/PS1ΔE9 transgenic (APP/PS1) mice were administered Dendrobium nobile Lindl. alkaloids (DNLA, 40 and 80 mg/kg) or Metformin (80 mg/kg), and age-matched wild-type mice were administered an isovolumic vehicle orally once a day for 4 months. The results demonstrated that DNLA significantly improved learning and memory function in APP/PS1 transgenic mice in the Morris water maze. Furthermore, DNLA could increase the expression of the v-ATPase A1 subunit to facilitate lysosomal acidification, prompt the dissociation of the cation independent-mannose-phosphate receptor from cathepsin (cat) D, promote the proteolytic maturation of cat D, increase the degradation of accumulated autophagic vacuoles (AVs) and β-amyloid (Aβ) contained in the AVs, and alleviate neuronal and synaptic injury. These findings demonstrate that DNLA improves learning and memory function in APP/PS1 mice, and the mechanisms appear to be due to the promotion of intracellular Aβ degradation by increasing the protein level of v-ATPase A1 and then improving autolysosomal acidification and proteolysis

Transcriptional Factor NF-κB as a Target for Therapy in Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative condition characterized by chronic inflammation. Nuclear factor κB (NF-κB) is a family of inducible transcription factors that are expressed in a wide variety of cells and tissues, including microglia, astrocytes, and neurons, and the classical NF-κB pathway plays a key role in the activation and regulation of inflammatory mediator production during inflammation. Activation of the classical NF-κB pathway is mediated through the activity of the IKK kinase complex, which consists of a heterotrimer of IKKα, IKKβ, and IKKγ subunits. Targeting NF-κB has been proposed as an approach to the treatment of acute and chronic inflammatory conditions, and the use of inhibitors specific for either IKKβ or IKKγ has now been found to inhibit neurodegeneration of TH+ DA-producing neurons in murine and primate models of Parkinson's disease. These studies suggest that targeting the classical pathway of NF-κB through the inhibition of the IKK complex can serve as a useful therapeutic approach to the treatment of PD

Suppression of decoherence by bath ordering

The dynamics of two coupled spins-1/2 coupled to a spin-bath is studied as an extended model of the Tessieri-Wilkie Hamiltonian \cite{TWmodel}. The pair of spins served as an open subsystem were prepared in one of the Bell states and the bath consisted of some spins-1/2 is in a thermal equilibrium state from the very beginning. It is found that with the increasing the coupling strength of the bath spins, the bath forms a resonant antiferromagnetic order. The polarization correlation between the two spins of the subsystem and the concurrence are recovered in some extent to the isolated subsystem. This suppression of the subsystem decoherence may be used to control the quantum devices in practical applications.Comment: 32 pages, Chinese Physics (accepted

Pressure-induced melting of magnetic order and emergence of new quantum state in alpha-RuCl3

Here we report the observation of pressure-induced melting of antiferromagnetic (AFM) order and emergence of a new quantum state in the honeycomb-lattice halide alpha-RuCl3, a candidate compound in the proximity of quantum spin liquid state. Our high-pressure heat capacity measurements demonstrate that the AFM order smoothly melts away at a critical pressure (Pc) of 0.7 GPa. Intriguingly, the AFM transition temperature displays an increase upon applying pressure below the Pc, in stark contrast to usual phase diagrams, for example in pressurized parent compounds of unconventional superconductors. Furthermore, in the high-pressure phase an unusual steady of magnetoresistance is observed. These observations suggest that the high-pressure phase is in an exotic gapped quantum state which is robust against pressure up to ~140 GPa.Comment: 20 pages, 4 figure