bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryonic cell migratory capacity is impaired upon exposure to glucose in vivo and in vitro
Authors: Herion Nils Janis , Kruger Claudia , Staszkiewicz Jaroslaw , Kappen Claudia , Salbaum J. Michael 
Published: November 2018

BackgroundImpairments in cell migration during vertebrate gastrulation lead to structural birth defects, such as heart defects and neural tube defects. These defects are more frequent in progeny from diabetic pregnancies, and we have recently provided evidence that maternal diabetes leads to impaired migration of embryonic mesodermal cells in a mouse model of diabetic pregnancy.MethodsWe here report the isolation of primary cell lines from normal and diabetes‐exposed embryos of the nonobese diabetic mouse strain, and characterization of their energy metabolism and expression of nutrient transporter genes by quantitative real‐time PCR.ResultsExpression levels of several genes in the glucose transporter and fatty acid transporter gene families were altered in diabetes‐exposed cells. Notably, primary cells from embryos with prior in vivo exposure to maternal diabetes exhibited reduced capacity for cell migration in vitro.ConclusionsPrimary cells isolated from diabetes‐exposed embryos retained a “memory” of their in vivo exposure, manifesting in cell migration impairment. Thus, we have successfully established an in vitro experimental model for the mesoderm migration defects observed in diabetes‐exposed mouse embryos.
Comprehensive analysis of the atenolol – DNA complex by viscometric, molecular docking and spectroscopic techniques
Authors: Kale Kishor B. , Ottoor Divya P. 
Published: November 2018

AbstractThis paper discusses multi‐spectroscopic and molecular docking analysis of the interaction between atenolol (ATN) and deoxyribose nucleic acid (DNA) using alizarin (ALZ) as a spectroscopic probe. ATN is a β1‐receptor antagonist belonging to the β‐blocker class of molecules. Experimental findings that were based on different spectroscopic analysis, melting studies, viscometric analysis, 1H nuclear magnetic resonance and circular dichroism studies revealed the presence of a grove‐binding mode. The effect of ionic strength was also studied, and observations suggested that electrostatic interaction also played a minor role during interaction. Molecular docking analysis suggested that the dominant force for the grove‐binding phenomenon was hydrogen bonding between the 24‐H residue of ATN and O of the 10‐G residue, and the 40‐H residue of ATN and N of the 17‐A base residue. Competitive binding study of the ALZ−DNA complex with ATN showed that, despite an increase in the amount of ATN in the ALZ−DNA complex, the overall absorbance remained unchanged. The decrease in fluorescence in the ALZ−DNA system may be due to new non‐fluorescent ATN−DNA−ALZ complex formation.
Enhanced production of glutaric acid by NADH oxidase and GabD‐reinforced bioconversion from l‐lysine
Authors: Hong Yun‐Gi , Moon Yu‐Mi , Choi Tae‐Rim , Jung Hye‐Rim , Yang Soo‐Yeon , Ahn Jung‐Oh , Joo Jeong‐Chan , Park Kyungmoon , Kim Yun‐Gon , Bhatia Shashi Kant , Lee Yoo Kyung , Yang Yung‐Hun 
Published: November 2018

AbstractGlutaric acid is a promising alternative chemical to phthalate plasticizer since it can be produced by the bioconversion of lysine. Though, recent studies have enabled the high‐yield production of its precursor, 5‐aminovaleric acid (AMV), glutaric acid production via the AMV pathway has been limited by the need for cofactors. Introduction of NAD(P)H oxidase (Nox) with GabTD enzyme remarkably diminished the demand for oxidized nicotinamide adenine dinucleotide (NAD+). Supply of oxygen through vigorous shaking had a significant effect on the conversion of AMV with a reduced requirement of NAD
+. A high conversion rate was achieved in Nox coupled GabTD reaction under optimized expression vector, terrific broth (TB), and pH 8.5 at high cell density. Supplementary expression of GabD resulted in the production of 353 ± 35 mM glutaric acid with 88.3 ± 8.7% conversion from 400 mM AMV. Moreover, the reaction with a higher concentration of AMV could produce 528 ± 21 mM glutaric acid with 66.0 ± 2.7% conversion. In addition, the co‐biotransformation strategy of GabTD and DavBA whole cells could produce 282 mM glutaric acid with 70.8% conversion from lysine, compared to the 111 mM glutaric acid yield from the combined GabTD–DavBA system.
Virus study for continuous low pH viral inactivation inside a coiled flow inverter
Authors: David Laura , Maiser Benjamin , Lobedann Martin , Schwan Peter , Lasse Michael , Ruppach Horst , Schembecker Gerhard 
Published: November 2018

AbstractContinuous processing for the production of monoclonal antibodies (mAb) gains more and more importance. Several solutions exist for all the necessary production steps, leading to the possibility to build fully continuous processes. Low pH viral inactivation is a part of the standard platform process for mAb production. Consequently, Klutz et al. introduced the coiled flow inverter (CFI) as a tool for continuous low pH viral inactivation. Besides theoretical calculations of viral reduction, no viral clearance study has been presented so far. In addition, the validation of continuous viral clearance is often neglected in the already existing studies for continuous processing.This study shows in detail the development and execution of a virus study for continuous low pH viral inactivation inside a CFI. The concept presented is also valid for adaptation to other continuous viral clearance steps. The development of this concept includes the technical rationale for an experimental setup, a valid spiking procedure, and finally a sampling method. The experimental results shown represent a viral study using xenotropic murine leukemia virus as a model virus. Two different protein A (ProtA) chromatography setups with varying pH levels were tested. In addition, one of these setups was tested against a batch experiment utilizing the same process material. The results show that sufficient low pH viral inactivation (decadic logarithm reduction value >4) was achieved in all experiments. Complete viral inactivation took place within the first 14.5 min for both continuous studies and the batch study, hence showing similar results. This study therefore represents a successful virus study concept and experiment for a continuous viral inactivation step. Moreover, it was shown that the transfer from batch results to the continuous process is possible. This is accomplished by the narrow residence time distribution of the CFI, showing how close the setup approaches the ideal plug flow and with that batch operation.
Combinatorial impact of Sec signal peptides from Bacillus subtilis and bioprocess conditions on heterologous cutinase secretion by Corynebacterium glutamicum
Authors: Hemmerich Johannes , Moch Matthias , Jurischka Sarah , Wiechert Wolfgang , Freudl Roland , Oldiges Marco 
Published: November 2018

AbstractThe impact of Sec signal peptides (SPs) from Bacillus subtilis in combination with isopropyl‐β‐
d‐1‐thiogalactopyranoside concentration and feeding profile was investigated for heterologous protein secretion performance by
Corynebacterium glutamicum using cutinase as model enzyme. Based on a comprehensive data set of about 150 bench‐scale bioreactor cultivations in fed‐batch mode and choosing the cutinase yield as objective, it was shown that relative secretion performance for bioprocesses remains very similar, irrespective of the applied SP enabling Sec‐mediated cutinase secretion. However, to achieve the maximal absolute cutinase yield, careful adjustment of bioprocess conditions was found to be necessary. A model‐based, two‐step multiple regression approach resembled the collected data in a comprehensive way. The corresponding results suggest that the choice of the heterologous Sec SP and its interaction with the adjusted exponential feeding profile is highly relevant to maximize absolute cutinase yield in this study. For example, the impact of Sec SP is high at low growth rates and low at high growth rates. However, promising Sec SPs could be inferred from less complex batch cultivations. The extensive data were also evaluated in terms of cutinase productivity, highlighting the well‐known trade‐off between yield and productivity in bioprocess development in detail. Conclusively, only the right combination of target protein, Sec SP, and bioprocess conditions is the key to success.
Creation and validation of a reactor engineering model for multiphase red wine fermentations
Authors: Miller Konrad V. , Oberholster Anita , Block David E. 
Published: November 2018

AbstractRed wine fermentations are performed in the presence of grape skins and seeds to ensure the extraction of color and other phenolics. The presence of these solids results in two distinct phases in the fermentor, as the solids float to the top to form a “cap.” Modeling of red wine fermentation is, therefore, complex and must consider spatial heterogeneity to predict fermentation kinetics. We have developed a reactor‐engineering model for red wine fermentations that includes the fundamentals of fermentation kinetics, heat transfer, diffusion, and compressible fluid flow. To develop the heat transfer component of the model, the heat transfer properties of grapes were experimentally determined as a function of fermentation progression. COMSOL was used to solve all components of the model simultaneously utilizing a finite element analysis approach. Predictions from this model were validated using prior experimental work. Model prediction and experimental data showed excellent agreement. The model was then used to predict spatial profiles of active yeast cell concentration and ethanol productivity, as well as liquid velocity profiles. Finally, the model was used to predict how these gradients would change with differences in initial bioavailable nitrogen concentration, a key parameter in predicting fermentation outcome in nitrogen‐limited wine fermentations.
Structure of an engineered intein reveals thiazoline ring and provides mechanistic insight
Authors: Pearson C. Seth , Nemati Reza , Liu Binbin , Zhang Jing , Scalabrin Matteo , Li Zhong , Li Hongmin , Fabris Dan , Belfort Marlene , Belfort Georges 
Published: November 2018

AbstractWe have engineered an intein which spontaneously and reversibly forms a thiazoline ring at the native N‐terminal Lys‐Cys splice junction. We identified conditions to stablize the thiazoline ring and provided the first crystallographic evidence, at 1.54 Å resolution, for its existence at an intein active site. The finding bolsters evidence for a tetrahedral oxythiazolidine splicing intermediate. In addition, the pivotal mutation maps to a highly conserved B‐block threonine, which is now seen to play a causative role not only in ground‐state destabilization of the scissile N‐terminal peptide bond, but also in steering the tetrahedral intermediate toward thioester formation, giving new insight into the splicing mechanism. We demonstrated the stability of the thiazoline ring at neutral pH as well as sensitivity to hydrolytic ring opening under acidic conditions. A pH cycling strategy to control N‐terminal cleavage is proposed, which may be of interest for biotechnological applications requiring a splicing activity switch, such as for protein recovery in bioprocessing.
Low‐cost customizable microscale toolkit for rapid screening and purification of therapeutic proteins
Authors: Andar Abhay U. , Deldari Sevda , Gutierrez Erick , Burgenson David , Al‐Adhami Mustafa , Gurramkonda Chandrasekhar , Tolosa Leah , Kostov Yordan , Frey Douglas D. , Rao Govind 
Published: November 2018

AbstractBiopharmaceutical separations require tremendous amounts of optimization to achieve acceptable product purity. Typically, large volumes of reagents and biological materials are needed for testing different parameters, thus adding to the expense of biopharmaceutical process development. This study demonstrates a versatile and customizable microscale column (µCol) for biopharmaceutical separations using immobilized metal affinity chromatography (IMAC) as an example application to identify key parameters. µCols have excellent precision, efficiency, and reproducibility, can accommodate any affinity, ion‐exchange or size‐exclusion‐based resin and are compatible with any high‐performance liquid chromatography (HPLC) system. µCols reduce reagent amounts, provide comparable purification performance and high‐throughput, and are easy to automate compared with current conventional resin columns. We provide a detailed description of the fabrication methods, resin packing methods, and µCol validation experiments using a conventional HPLC system. Finite element modeling using COMSOL Multiphysics was used to validate the experimental performance of the µCols. In this study, µCols were used for improving the purification achieved for granulocyte colony stimulating factor (G‐CSF) expressed using a cell‐free CHO in vitro translation (IVT) system and were compared to a conventional 1 ml IMAC column. Experimental data revealed comparable purity with a 10‐fold reduction in the amount of buffer, resin, and purification time for the μCols compared with conventional columns for similar protein yields.
Doxorubicin‐induced heart failure in cancer patients: A cohort study based on the Korean National Health Insurance Database
Authors: Kim Young Ae , Cho Hyunsoon , Lee Nayoung , Jung So‐Youn , Sim Sung Hoon , Park In Hae , Lee Sunmi , Lee Eun Sook , Kim Hak Jin 
Published: November 2018

AbstractBackgroundDoxorubicin is a typical anticancer drug that causes cardiomyopathy and heart failure (HF). The aim of our study was to investigate incidence, risk factors for doxorubicin‐induced HF in Korean cancer patients and their survival rate, utilizing a nationwide population‐based cohort.MethodsWe analyzed 58 541 cancer patients who received doxorubicin between 2003 and 2010. Descriptive analysis was performed in patients with breast cancer, hematologic malignancy, gynecological malignancy, and sarcoma. Risk factors associated with doxorubicin‐induced HF were investigated using a Cox proportional hazards model. The survival rate of doxorubicin‐induced HF patients was compared with that of patients without doxorubicin‐induced HF.ResultsA total of 2324 (4%) were diagnosed with doxorubicin‐induced HF. In patients with breast cancer, predictive risk factors for doxorubicin‐induced HF included age over 65 years [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.05‐1.72], hypertension [HR 2.45 (2.12‐ 2.84)], diabetes mellitus [HR 1.26 (1.05‐1.51)], coronary artery disease [HR 2.08 (1.63‐2.66)], advanced stage [HR 1.31 (1.13‐1.50)], and trastuzumab administration [HR 2.94 (2.54‐3.40)]. In patients with hematologic malignancy, predictive risk factors included age over 65 years [HR 1.75 (1.49‐2.07)], hypertension [HR 1.62 (1.37‐1.92)], and coronary artery disease [HR 2.28 (1.80‐2.89)]. Five‐year survival rates of patients with doxorubicin‐induced HF were significantly lower relative to those of patients without HF in breast cancer and hematologic malignancy: 80% vs 84% and 69% vs 75%, respectively (P < 0.001).ConclusionsIn cancer patients treated with doxorubicin, management of risk factors, early detection, and treatment for doxorubicin‐induced HF might be critical for patient survival.
Quantifying the Relationship between Attention‐Deficit/Hyperactivity Disorder and Experiences of Child Maltreatment: A Meta‐Analysis
Authors: Clayton Kylee , Lee Janelle Boram , Cheung Kristene , Theule Jennifer , Henrikson Brenna 
Published: November 2018

The purpose of this study was to examine the association between attention‐deficit/hyperactivity disorder (ADHD) and experiences of child maltreatment. This study employed several meta‐analyses. Studies included in the meta‐analysis contained a comparison of experiences of child maltreatment in individuals with and without ADHD or assessed the relationship between ADHD symptoms and experiences of child maltreatment. There were 18 studies that met the eligibility criteria. Individuals with ADHD had higher odds of having been maltreated in childhood compared to individuals without ADHD (odds ratio = 2.39, p < 0.001). There was a significant association between ADHD symptoms and experiences of child maltreatment (r = 0.28, p < 0.001). Clinicians need to be cognisant of the risk of child maltreatment when working with individuals with ADHD, and vice versa.‘Examine[s] the association between ADHD and experiences of child maltreatment’
Antineoplastic Constituents from the Chemical Diversified Extract ofRadix puerariae
Authors: Zhang Jian‐Long , Xu Wei , Zhou Zhen‐Ru , Li Juan , Jiang Lin‐Lin , Zhang Xing‐Xiao , Jiang Ren‐Wang 
Published: November 2018

AbstractTo enhance the structural diversity of isoflavonoids and provide more derivatives for the biological screening, a semisynthetic mixture was generated by diversification of the crude extract ofRadix puerariae(Pueraria montanavar. lobata) through the chemical reaction with hydrazine hydrate. Eleven 3,4‐diarylpyrazoles (1–11) and two 5‐phenyl‐6‐benzyldihydropyridazinones (12and13) were isolated from the semisynthetic mixture, and their structures were identified by spectroscopic methods in combination with X‐ray crystallographic analysis. Among them, nine compounds (5–13) were new derivatives. All the compounds were evaluated on the inhibitory activities against the prostate cancer cell lines LNCaP and PC3. Compounds12and13were found to exhibit much more potent inhibitory activities against the androgen dependent LNCaP cells than the androgen independent PC3 cells. Rapid synthesis of new 3,4‐diarylpyrazoles and two 5‐phenyl‐6‐benzyldihydropyridazinones with significant biological activity highlights the great potential of one‐pot combinatorial modification for the diversification of natural products.
Therapy‐related acute myeloid leukemia after chemotherapy in extensive disease‐small cell lung cancer
Authors: Ueda Naoko , Fujita Kohei , Okuno Yoshiaki , Nakatani Koichi , Mio Tadashi 
Published: November 2018

Key Clinical MessageWe experienced therapy‐related acute myeloid leukemia (t‐AML) in a patient with extensive disease‐small cell lung cancer (ED‐SCLC). This case is rare and has educational message because ED‐SCLC has a poor prognosis and often cannot survive until developing therapy related hematological malignancy. Furthermore this case had unique chromosomal abnormalities. With recent advances in chemotherapy and radiotherapy, the prognosis of lung cancer has improved, while t‐AML has been increasing in frequency.
One‐Shot Measurement of Effectiveness Factors of Chemical Conversion in Porous Catalysts
Authors: Chmelik Christian , Liebau Michael , Al‐Naji Majd , Möllmer Jens , Enke Dirk , Gläser Roger , Kärger Jörg 
Published: November 2018

AbstractFrom the earliest days of heterogeneous catalysis, high surface area solids were extensively used for attaining largest possible densities of active sites and, correspondingly, for maximizing turnover. Since sites are active in the real sense of the word only if they are occupied by reactants, i. e., by molecules still to be converted, the relative fraction of pore volume occupied by reactants (the “effectiveness factor”) is a key number for the efficiency of a catalyst in a given reaction. Its determination, so far generally based on reaction rate measurements with purposefully varied catalyst particles, remained to date a challenging task since it must be based on additional assumptions. The “one‐shot determination” of effectiveness factors by IR microimaging, here exemplified on considering the catalytic hydrogenation of benzene to cyclohexane by platinum dispersed on nanoporous glass, is shown to open up a promising route to overcome these limitations.
Toward High‐Voltage, Energy‐Dense, and Durable Aqueous Organic Redox Flow Batteries: Role of the Supporting Electrolytes
Authors: Chen Ruiyong 
Published: November 2018

AbstractSustainable energy supply from renewable sources requires highly efficient and economically competitive energy‐storage technologies. With flexible design, high energy‐storage efficiency, and long‐term cyclability, redox flow batteries are superior candidates for peak shaving and load leveling for smart grids in the energy generation, storage and distribution networks. With natural abundance, structural diversity and tunability, redox‐active organic species as valuable alternatives to the traditional inorganic‐based materials are promising to tackle the resource and performance limitations. To design aqueous organic redox flow batteries toward energy‐dense, high‐rate performance and durability, in this Review, strategies to maximize the cell voltage, effective concentration of organic species, and operating current density are discussed. Besides the inherent nature of the organic molecules, suitable solvents and supporting ions can affect their solvation behavior and promote their chemical stability.
Conductive Polypyrrole Coated Hollow NiCo2O4 Microspheres as Anode Material with Improved Pseudocapacitive Contribution and Enhanced Conductivity for Lithium‐Ion Batteries
Authors: Luo Yani , Guo Ruisong , Li Tingting , Li Fuyun , Meng Leichao , Yang Zhiwei , Wan Yizao , Luo Honglin 
Published: November 2018

AbstractConductive polypyrrole (PPy) coated urchin‐like hollow NiCo2O4 (NCO) porous microspheres (NCO@PPy) were synthesized by an easy and cost‐effective method. The NCO@PPy shows improved cycling stability and rate capability in comparison with the pure NiCo2O4 when used as anode material for lithium‐ion batteries. In order to undersatnd the improvement of electrochemical performance of NCO@PPy, kinetic parameters and the lithium storage mechanism are investigated by EIS spectra and sweep voltammetry measurements. The sweep‐rate‐dependent CV (cyclic voltammetry) curves demonstrate an ever‐increasing redox capacitive‐controlled lithium storage originating from both, the hierarchical hollow structure and the effect of the PPy coating layer. The apparent Li+ ion diffusion coefficient of NCO@PPy and NCO derived from EIS and CV curves indicates that PPy coating layer reduces the charge‐transfer resistances and improves the lithium‐ion diffusion coefficient.
Efficient variable selection algorithm adopting variance inflated resampling weight vector into model population analysis
Authors: Mahanty Biswanath 
Published: November 2018

AbstractVariable iterative space shrinkage approach (VISSA) is an important variable selection algorithm known for its improved accuracy and outcome stability in partial least squares (PLS) regression models. However, time efficiency of VISSA is not very promising. In this work, three strategies to inflate the variance of resampling weight vector (RWV) have been proposed to accelerate the space shrinkage in VISSA. The original RWV (ie, average binary frequency of variables) is replaced with average of unit normalized regression coefficients (UNRC), fitness normalized regression coefficients (FNRC), or logarithmically transformed regression coefficients (LTRC) of selected PLS sub‐models. Although prediction efficiencies for UNRC and FNRC are marginally inferior to the original binary‐weight VISSA, the stability of retained variables and remarkable improvements in algorithm speed is evident for relatively large size NIR data set (700 variables). LTRC with moderate degree of RWV variance inflation is indisputably a better choice. Chimeric algorithm, incorporating UNRC, FNRC, or LTRC in first round of original VISSA, maintained the model fitness per se while significantly improving time efficiency. With small dimensional NIR data set (100 variables), proposed weighting schemes have no additional advantage over original VISSA implementation.