bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pheophytin Derived Near‐Infrared‐Light Responsive Carbon Dot Assembly as a New Phototheranotic Agent for Bioimaging and Photodynamic Therapy
Authors: Wen Yongmei , Jia Qingyan , Nan Fuchun , Zheng Xiuli , Liu Weimin , Wu Jiasheng , Ren Haohui , Ge Jiechao , Wang Pengfei 
Published: May 2019

AbstractCarbon dots (CDs), a kind of phototheranostic agent with the capability of simultaneous bioimaging and phototherapy [i.e., photodynamic therapy (PDT) or photothermal therapy (PTT)], have received considerable attention because of their remarkable properties, including flexibility for surface modification, high biocompatibility, low toxicity and photo‐induced activity for malignant tumor cells. Among numerous carbon sources, it has been found that natural biomass are good candidates for the preparation of CD phototheranostic agents. In this study, pheophytin, a type of Mg‐free chlorophyll derivative and also a natural product with low toxicity, was used as a raw carbon source for the synthesis of CDs by using a microwave method. The obtained hydrophobic CDs exhibited a maximum near‐infrared (NIR) emission peak at approximately 680 nm, and high singlet oxygen (1O2) generation with a quantum yield of 0.62. The self‐assembled CDs from the as‐prepared CDs with DSPE‐mPEG2000 retained efficient 1O2 generation. The obtained carbon dot assembly was not only an efficient fluorescence (FL) imaging agent but also a smart PDT agent. Our studies indicated that the obtained hydrophilic CD assembly holds great potential as a new phototheranostic agent for cancer therapy. This work provides a new route for synthesis of CDs and proposes a readily available candidate for tumor treatment.
Near‐optimal control for a stochastic SIRS model with imprecise parameters
Authors: Mu Xiaojie , Zhang Qimin , Rong Libin 
Published: May 2019

AbstractParameter values are usually assumed to be precisely known in many epidemic models but they could be imprecise due to various uncertainties. In this paper, we develop a stochastic SIRS model that includes imprecise parameters and white noise, formulate and analyze the near‐optimal control problem for the stochastic model. We obtain priori estimates of the susceptible, infected and recovered populations. Sufficient and necessary conditions for the near optimality of the model are established using Ekeland's principle and a nearly maximum condition on the Hamiltonian function. Numerical simulations are also performed to demonstrate the analytical results and evaluate the influence of imprecise parameters, white noise and treatment control on the dynamics of epidemics.
Adaptive dynamic surface control of switched MIMO nonlinear systems with input saturation and its application to NSVs
Authors: Ye Bohong , Long Lijun , Zhao Jun 
Published: May 2019

AbstractIn this paper, the problem of adaptive tracking control is addressed for a class of switched multi‐input multi‐output (MIMO) nonlinear systems in the presence of external disturbance and input saturation. To efficiently handle the external disturbance, a switched Nussbaum disturbance observer is designed. Also, a switched auxiliary system is constructed to compensate for the effect of the input saturation, which extends the classical control technique from its original non‐switched version to a switched version. A switched dynamic surface control technique is set up by exploiting the common Lyapunov function (CLF) method and backstepping and the Nussbaum gain technique, which overcomes the problem of “explosion of complexity" in the backstepping control designed. It is shown that the proposed control technique is able to guarantee semiglobal uniformly ultimately boundedness of all signals in the closed‐loop system under arbitrary switchings, and the tracking error converges to a small neighborhood of the origin. Finally, the effectiveness of the proposed control technique is illustrated by its application to a variable structure near space vehicle (NSV) with input saturation.
Matrix approach to simplification of finite state machines using semi‐tensor product of matrices
Authors: Yue Jumei , Yan Yongyi , Chen Zengqiang 
Published: May 2019

AbstractIn this paper, we use a new mathematical tool, semi‐tensor product of matrices, to investigate the problem of simplification of finite state machines (FSMs) in a mathematical manner. First, based on the dynamic equations of state transition and output behavior which are developed recently, an algebraic criterion of k‐difference states is established. Second, using the criterion, a scheme is designed to construct the incompatible graphs of FSMs. Third, with the incompatible graphs and the method of searching internally stable sets of graphs proposed by the authors, a solution is proposed to obtain all of the compatible state set (CSS) of FSMs. Then, with the aid of the CSS, we investigate three kinds of structures of state space of FSMs, including compatible cover of state set (CCSS), representative set of state set (RSSS), and minimum representative set of state set (MRSSS); necessary and sufficient conditions are proposed to formulate the three kinds of structures. Finally, examples are given to exemplify minimum realizations of FSMs by these conditions.
New spectrofluorimetric analysis of dapagliflozin after derivatization with NBD‐Cl in human plasma using factorial design experiments
Authors: Omar Mahmoud A. , Ahmed Hytham M. , Abdel Hamid Mohamed A. , Batakoushy Hany A. 
Published: May 2019

AbstractA new validated spectrofluorimetric method was proposed for dapagliflozin (DGF) analysis in bulk, plexin its commercially available tablets and in spiked human plasma. The proposed spectrofluorimetric method depended on the formation of a fluorescent complex soluble in organic liquids by a substitution reaction between 4‐chloro‐7‐nitrobenzo‐2‐oxa‐1,3‐diazole (NBD‐Cl) reagent and DGF in aqueous buffered solution at pH 7. The fluorescence intensity was measured at 522 nm after excitation at 453 nm. The high selectivity of the proposed method allowed analysis of DGF in dosage form and human plasma samples with average recovery values of 99.84 ± 1.38% and 98.71 ± 1.80%, respectively, without any interference from matrix components. The calibration range was 50–1000 ng ml−1. The limit of detection (LOD) and limit of quantitation (LOQ) were 14.24 ng ml−1 and 43.14 ng ml−1, respectively. The estimated relative standard deviation values were lower than 2.0%, this showed the excellent precision at both levels. Factorial design was used to get the optimum method conditions for the analysis of the resulting DGF fluorescence complex in different matrices. The proposed method could be used in routine analysis of DGF in quality control laboratories. Also, it could be used to assay DGF in human plasma and be applied for pharmacokinetic investigation of DGF.
Adaptive laboratory evolution of nanocellulose‐producing bacterium
Authors: Vasconcellos Vanessa M. , Farinas Cristiane S. , Ximenes Eduardo , Slininger Patricia , Ladisch Michael 
Published: May 2019

AbstractAdaptive laboratory evolution through 12 rounds of culturing experiments of the nanocellulose‐producing bacterium Komagataeibacter hansenii ATCC 23769 in a liquid fraction from hydrothermal pretreatment of corn stover resulted in a strain that resists inhibition by phenolics. The original strain generated nanocellulose from glucose in standard Hestrin and Schramm (HS) medium, but not from the glucose in pretreatment liquid. K. hansenii cultured in pretreatment liquid treated with activated charcoal to remove inhibitors also converted glucose to bacterial nanocellulose and used xylose as carbon source for growth. The properties of this cellulose were the same as nanocellulose generated from media specifically formulated for bacterial cellulose formation. However, attempts to directly utilize glucose proved unsuccessful due to the toxic character of the lignin‐derived phenolics, and in particular, vanillan and ferulic acid. Adaptive laboratory evolution at increasing concentrations of pretreatment liquid from corn stover in HS medium resulted in a strain of K. hansenii that generated bacterial nanocellulose directly from pretreatment liquids of corn stover. The development of this adapted strain positions pretreatment liquid as a valuable resource since K. hansenii is able to convert and thereby concentrate a dilute form of glucose into an insoluble, readily recovered and value‐added product—bacterial nanocellulose.
Process design and development of a mammalian cell perfusion culture in shake‐tube and benchtop bioreactors
Authors: Wolf Moritz K. F. , Müller Andrea , Souquet Jonathan , Broly Hervé , Morbidelli Massimo 
Published: May 2019

AbstractThe development of mammalian cell perfusion cultures is still laborious and complex to perform due to the limited availability of scale‐down models and limited knowledge of time‐ and cost‐effective procedures. The maximum achievable viable cell density (VCDmax), minimum cell‐specific perfusion rate (CSPRmin), cellular growth characteristics, and resulting bleed rate at steady‐state operation are key variables for the effective development of perfusion cultures. In this study, we developed a stepwise procedure to use shake tubes (ST) in combination with benchtop (BR) bioreactors for the design of a mammalian cell perfusion culture at high productivity (23 pg·cell−1·day−1) and low product loss in the bleed (around 10%) for a given expression system. In a first experiment, we investigated peak VCDs in STs by the daily discontinuous medium exchange of 1 reactor volume (RV) without additional bleeding. Based on this knowledge, we performed steady‐state cultures in the ST system using a working volume of 10 ml. The evaluation of the steady‐state cultures allowed performing a perfusion bioreactor run at 20 × 106 cells/ml at a perfusion rate of 1 RV/day. Constant cellular environment and metabolism resulted in stable product quality patterns. This study presents a promising strategy for the effective design and development of perfusion cultures for a given expression system and underlines the potential of the ST system as a valuable scale‐down tool for perfusion cultures.
A mechanistic model for gas–liquid mass transfer prediction in a rocking disposable bioreactor
Authors: Bai Yun , Moo‐Young Murray , Anderson William A. 
Published: May 2019

AbstractRocking disposable bioreactors are a newer approach to smaller‐scale cell growth that use a cyclic rocking motion to induce mixing and oxygen transfer from the headspace gas into the liquid. Compared with traditional stirred‐tank and pneumatic bioreactors, rocking bioreactors operate in a very different physical mode and in this study the oxygen transfer pathways are reassessed to develop a fundamental mass transfer (kLa) model that is compared with experimental data. The model combines two mechanisms, namely surface aeration and oxygenation via a breaking wave with air entrainment, borrowing concepts from ocean wave models. Experimental data for across the range of possible operating conditions (rocking speed, angle, and liquid volume) confirms the validity of the modeling approach, with most predictions falling within ±20% of the experimental values. At low speeds (up to 20 rpm) the surface aeration mechanism is shown to be dominant with a of around 3.5 hr−1, while at high speeds (40 rpm) and angles the breaking wave mechanism contributes up to 91% of the overall (65 hr−1). This model provides an improved fundamental basis for understanding gas–liquid mass transfer for the operation, scale‐up, and potential design improvements for rocking bioreactors.
Enzyme‐mediated hydrogel encapsulation of single cells for high‐throughput screening and directed evolution of oxidoreductases
Authors: Vanella Rosario , Ta Duy Tien , Nash Michael A. 
Published: May 2019

AbstractDirected evolution of oxidoreductases to improve their catalytic properties is being ardently pursued in the industrial, biotechnological, and biopharma sectors. Hampering this pursuit are current enzyme screening methods that are limited in terms of throughput, cost, time, and complexity. We present a directed evolution strategy that allows for large‐scale one‐pot screening of glucose oxidase (GOx) enzyme libraries in well‐mixed homogeneous solution. We used GOx variants displayed on the outer cell wall of yeasts to initiate a cascade reaction with horseradish peroxidase (HRP), resulting in peroxidase‐mediated phenol cross‐coupling and encapsulation of individual cells in well‐defined fluorescent alginate hydrogel shells within ~10 min in mixed cell suspensions. Following application of denaturing stress to whole‐cell GOx libraries, only cells displaying GOx variants with enhanced stability or catalytic activity were able to carry out the hydrogel encapsulation reaction. Fluorescence‐activated cell sorting was then used to isolate the enhanced variants. We characterized three of the newly evolved Aspergillus niger GOx enzyme sequences and found up to ~5‐fold higher specific activity, enhanced thermal stability, and differentiable glycosylation patterns. By coupling intracellular gene expression with the rapid formation of an extracellular hydrogel capsule, our system improves high‐throughput screening for directed evolution of H
2O
2‐producing enzymes many folds.
Progress in the study of virus detection methods: The possibility of alternative methods to validate virus inactivation
Authors: Zhang Yu , Qu Shuxin , Xu Liming 
Published: May 2019

AbstractVirus inactivation validation studies have been widely applied in the risk assessment of biogenic material‐based medical products, such as biological products, animal tissue‐derived biomaterials, and allogeneic biomaterials, to decrease the risk of virus transmission. Traditional virus detection methods in an inactivation validation study utilize cell culture as a tool to quantify the infectious virus by observing cytopathic effects (CPEs) after virus inactivation. However, this is susceptible to subjective factors because CPEs must be observed by experts under a microscope during virus titration. In addition, this method is costly and time‐ and labor‐consuming. Molecular biological technologies such as quantitative polymerase chain reaction (qPCR) have been widely used for virus detection but cannot distinguish infectious and noninfectious viruses. Therefore, qPCR cannot be directly applied to virus inactivation validation studies. In this paper, methods to detect viruses and progress in the challenge of differentiating infectious and noninfectious viruses with the combination of pretreatment and qPCR techniques such as the integrated cell culture‐qPCR (ICC‐qPCR) method are reviewed. In addition, the advantages and disadvantages of each new method, as well as its prospect in virus inactivation validation studies, are discussed.
Adhesive thermosensitive gels for local delivery of viral vectors
Authors: Caronia Jeanette M. , Sorensen Daniel W. , Leslie Hope M. , van Berlo Jop H. , Azarin Samira M. 
Published: May 2019

AbstractLocal delivery of viral vectors can enhance the efficacy of therapies by selectively affecting necessary tissues and reducing the required vector dose. Pluronic F127 is a thermosensitive polymer that undergoes a solution–gelation (sol–gel) transition as temperature increases and can deliver vectors without damaging them. While pluronics can be spread over large areas, such as the surface of an organ, before gelation, they lack sufficient adhesivity to remain attached to some tissues, such as the surface of the heart or mucosal surfaces. Here, we utilized blends of pluronic F127 and polycarbophil (PCB), a mucoadhesive agent, to provide the necessary adhesivity for local delivery of viral vectors to the cardiac muscle. The effects of PCB concentration on adhesive properties, sol–gel temperature transition and cytocompatibility were evaluated. Rheological studies showed that PCB decreased the sol–gel transition temperature at concentrations >1% and increased the adhesive properties of the gel. Furthermore, these gels were able to deliver viral vectors and transduce cells in vitro and in vivo in a neonatal mouse apical resection model. These gels could be a useful platform for delivering viral vectors over the surface of organs where increased adhesivity is required.
Highly selective enrichment of phosphopeptides using poly(dibenzo‐18‐crown‐6) as a solid‐phase extraction material
Authors: Mirza Munazza Raza , Rainer Matthias , Duran Shahid , Moin Syed Tarique , Choudhary M. Iqbal , Bonn Günther K. 
Published: May 2019

AbstractA poly(dibenzo‐18‐crown‐6) was used as a new solid‐phase extraction material for the selective enrichment of phosphopeptides. Isolation of phosphopeptides was achieved based on specific ionic interactions between poly(dibenzo‐18‐crown‐6) and the phosphate group of phosphopeptides. Thus, a method was developed and optimized, including loading, washing and elution steps, for the selective enrichment of phosphopeptides. To assess this potential, tryptic digest of three proteins (α‐ casein, β‐casein and ovalbumin) was applied on poly(dibenzo‐18‐crown‐6). The nonspecific products were removed by centrifugation and washing. The spectrometric analysis was performed using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. Highly selective enrichment of both mono‐ and multiphosphorylated peptides was achieved using poly(dibenzo‐18‐crown‐6) as solid‐phase extraction material with minimum interference from nonspecific compounds. Furthermore, evaluation of the efficiency of the poly(dibenzo‐18‐crown‐6) was performed by applying the digest of egg white. Finally, quantum mechanical calculations were performed to calculate the binding energies to predict the affinity between poly(dibenzo‐18‐crown‐6) and various ligands. The newly identified solid‐phase extraction material was found to be a highly efficient tool for phosphopeptide recovery from tryptic digest of proteins.
The prognostic comparison among unilateral, bilateral, synchronous bilateral, and metachronous bilateral breast cancer: A meta‐analysis of studies from recent decade (2008‐2018)
Authors: Pan Bo , Xu Ying , Zhou Yi‐Dong , Yao Ru , Wu Huan‐Wen , Zhu Qing‐Li , Wang Chang‐Jun , Mao Feng , Lin Yan , Shen Song‐Jie , Sun Qiang 
Published: May 2019

AbstractBackgroundThe incidence of bilateral breast cancer (BBC) is increasing nowadays comprising 2%‐11% of all breast cancer (BC). According to the interval time between the first and second cancer, BBC could be divided into synchronous (SBBC) and metachronous (MBBC). However, this interval time is quite different across studies. It remains controversial whether the survival of BBC, SBBC, and MBBC is similar or worse compared to that of unilateral breast cancer (UBC), and whether the survival of SBBC is similar or worse compared to MBBC. To better understand the survival of UBC, BBC, SBBC, and MBBC and how the interval time would influence the prognosis of SBBC and MBBC, we performed this meta‐analysis on studies from recent 10 years (2008‐2018).MethodsDatabases of PubMed, Embase, and Web of Science were searched for relevant studies within recent 10 years. Hazard ratio (HR) was adopted to evaluate the difference of overall survival (OS) of UBC, BBC, SBBC, and MBBC. HR of OS comparisons were performed between BBC vs UBC, SBBC vs UBC, MBBC vs UBC, and SBBC vs MBBC with 3, 6, 12 months as the interval time, respectively.ResultsThere were 15 studies of 72 302 UBC and 2912 BBC included in the meta‐analysis. The summary HR of OS comparison between BBC vs UBC was 1.68 (95% CI: 1.28‐2.20), SBBC vs UBC was 2.01 (95% CI: 1.14‐3.55), MBBC vs UBC was 3.22 (95% CI: 0.75‐13.78). When 3, 6, 12 months were used as the interval time, the summary HR of the OS comparison between of SBBC vs MBBC were 0.64 (95% CI: 0.44‐0.94), 1.17 (95% CI: 0.84‐1.63) and 1.45 (95% CI: 1.10‐1.92), respectively.ConclusionBBC and SBBC showed worse prognosis in terms of OS compared to UBC while MBBC manifested similar or non‐superior survival as UBC. The OS comparison between SBBC and MBBC changed with different interval time used. The longer the interval time used, the worse the survival of SBBC. SBBC with interval of 3‐12 months between the two cancers had the worst prognosis. When 6 months was used to differentiate SBBC from MBBC, these two clinical entities showed similar OS.
Dynamic Synthetic Cells Based on Liquid–Liquid Phase Separation
Authors: Martin Nicolas 
Published: May 2019

AbstractLiving cells have long been a source of inspiration for chemists. Their capacity of performing complex tasks relies on the spatiotemporal coordination of matter and energy fluxes. Recent years have witnessed growing interest in the bottom‐up construction of cell‐like models capable of reproducing aspects of such dynamic organisation. Liquid–liquid phase‐separation (LLPS) processes in water are increasingly recognised as representing a viable compartmentalisation strategy through which to produce dynamic synthetic cells. Herein, we highlight examples of the dynamic properties of LLPS used to assemble synthetic cells, including their biocatalytic activity, reversible condensation and dissolution, growth and division, and recent directions towards the design of higher‐order structures and behaviour.
Calmodulin‐like skin protein suppresses the increase in senescence‐associated β‐galactosidase induced by hydrogen peroxide or ultraviolet irradiation in keratinocytes
Authors: Takahara Yusuke , Miyachi Nobuyuki , Nawa Mikiro , Matsuoka Masaaki 
Published: May 2019

AbstractCalmodulin‐like skin protein (CLSP) is a secreted peptide that is produced by skin keratinocytes and some related epithelial cells. It has previously been shown that CLSP is recruited via the bloodstream into the central nervous system where it likely exerts a neuroprotective effect against toxicity related to Alzheimer's disease (AD) by binding to the heterotrimeric humanin receptor and activating intracellular survival signaling. However, it remains to be elucidated whether secreted CLSP shows a protective effect in the skin tissues. In the current study, using primary keratinocytes treated with hydrogen peroxide (H2O2) or exposed to ultraviolet (UV) irradiation as senescence models of keratinocytes, we addressed whether CLSP affects senescence in skin keratinocytes. We found that CLSP expression was upregulated by H2O2 or UV in keratinocytes. Furthermore, co‐incubation with recombinant CLSP reduced the increase in senescence‐associated β‐galactosidase‐positivity in keratinocytes that were induced by H2O2 or UV. These results suggest that CLSP may function as a senescence‐suppressing factor in keratinocytes.