bluuebunny/crossref_metadata_2025_split huggingface dataset:
Halogen‐Dependent Surface Confinement Governs Selective Alkane Functionalization to Olefins
Authors: Zichittella Guido , Scharfe Matthias , Puértolas Begoña , Paunović Vladimir , Hemberger Patrick , Bodi Andras , Szentmiklósi László , López Núria , Pérez‐Ramírez Javier 
Published: January 2019

AbstractThe product distribution in direct alkane functionalization by oxyhalogenation strongly depends on the halogen of choice. We demonstrate that the superior selectivity to olefins over an iron phosphate catalyst in oxychlorination is the consequence of a surface‐confined reaction. By contrast, in oxybromination alkane activation follows a gas‐phase radical‐chain mechanism and yields a mixture of alkyl bromide, cracking, and combustion products. Surface‐coverage analysis of the catalyst and identification of gas‐phase radicals in operando mode are correlated to the catalytic performance by a multi‐technique approach, which combines kinetic studies with advanced characterization techniques such as prompt‐gamma activation analysis and photoelectron photoion coincidence spectroscopy. Rationalization of gas‐phase and surface contributions by density functional theory reveals that the molecular level effects of chlorine are pivotal in determining the stark selectivity differences. These results provide strategies for unraveling detailed mechanisms within complex reaction networks.
Study on single and binary catalytic systems of pyridine‐imine catalysts based on nickel and iron in synthesis of reactor blends and low‐density polyethylene nanocomposites
Authors: Mogheiseh Mohsen , Zohuri Gholam Hossein , Khoshsefat Mostafa 
Published: January 2019

ABSTRACTIn the presence of modified methylaluminoxane as cocatalyst, the behavior of a binary catalytic system based on pyridine‐imine nickel (N) and iron (F) catalysts was evaluated in order to reach a proper mixture of polyethylene (PE). A computational study along with kinetic profile suggested that the catalyst F with higher electron affinity (A) and electrophilicity (ω) in the methyl cationic active center and stronger interaction with the monomer led to high integrated monomer consumption and higher activity. In addition, the samples produced by the mixture of catalysts showed a higher value of [19.4 × 104 g (PE) mol (Fe+Ni)−1 h−1)], melting point (127.8 °C), and crystallinity extent (41.29%) than the samples produced by the single catalysts. The addition of multiwalled carbon nanotubes (MWCNT) into the polymerization media reduced the activity of catalysts [from 7.50 × 104 to 0.66 × 104 g (PE) mol (Fe+Ni)−1 h−1] and the thermal properties of the low‐density polyethylene nanocomposite samples. However, the sample containing 2.33% MWCNT20‐30 improved the total thermal stability of the neat polyethylene blend up to 400 °C. Scanning electron microscope images of the samples demonstrated irregular to virtually uniform morphologies were obtained through the in situ and solution‐mixing techniques. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47376.
Oligoamide Foldamers as Helical Chloride Receptors—the Influence of Electron‐Withdrawing Substituents on Anion‐Binding Interactions
Authors: Helttunen Kaisa , Annala Riia , Suhonen Aku , Iloniemi Juho , Kalenius Elina , Aragay Gemma , Ballester Pablo , Tuononen Heikki M. , Nissinen Maija 
Published: January 2019

AbstractThe anion‐binding properties of three closely related oligoamide foldamers were studied using NMR spectroscopy, isothermal titration calorimetry and mass spectrometry, as well as DFT calculations. The 1H NMR spectra of the foldamers in [D6]acetone solution revealed partial preorganization by intramolecular hydrogen bonding, which creates a suitable cavity for anion binding. The limited size of the cavity, however, enabled efficient binding by the inner amide protons only for the chloride anion resulting in the formation of a thermodynamically stable 1:1 complex. All 1:1 chloride complexes displayed a significant favourable contribution of the entropy term. Most likely, this is due to the release of ordered solvent molecules solvating the free foldamer and the anion to the bulk solution upon complex formation. The introduction of electron‐withdrawing substituents in foldamers 2 and 3 had only a slight effect on the thermodynamic constants for chloride binding compared to the parent receptor. Remarkably, the binding of chloride to foldamer 3 not only produced the expected 1:1 complex but also open aggregates with 1:2 (host:anion) stoichiometry.
Squaraine Dyes: Interaction with Bovine Serum Albumin to Investigate Supramolecular Adducts with Aggregation‐Induced Emission (AIE) Properties
Authors: Barbero Nadia , Butnarasu Cosmin , Visentin Sonja , Barolo Claudia 
Published: January 2019

AbstractBovine serum albumin (BSA)–squaraine supramolecular adducts with aggregation‐induced emission (AIE) properties were prepared and characterized by spectroscopic methods. While squaraine dyes showed a very low fluorescence quantum yield in water, a great enhancement in the fluorescence of the aggregated BSA adducts was achieved due to the abnormal aggregation‐induced emission properties of squaraines. The adducts formation was studied from a kinetic point of view showing unexpected structure–properties relationships.
Estimation of log‐odds ratio from group testing data using Firth correction
Authors: Roy Surupa , Banerjee Tathagata 
Published: January 2019

AbstractWe consider the estimation of the prevalence of a rare disease, and the log‐odds ratio for two specified groups of individuals from group testing data. For a low‐prevalence disease, the maximum likelihood estimate of the log‐odds ratio is severely biased. However, Firth correction to the score function leads to a considerable improvement of the estimator. Also, for a low‐prevalence disease, if the diagnostic test is imperfect, the group testing is found to yield more precise estimate of the log‐odds ratio than the individual testing.
Control of IgG glycosylation by in situ and real‐time estimation of specific growth rate of CHO cells cultured in bioreactor
Authors: Li Meng‐Yao , Ebel Bruno , Blanchard Fabrice , Paris Cédric , Guedon Emmanuel , Marc Annie 
Published: January 2019

AbstractThe cell‐specific growth rate (µ) is a critical process parameter for antibody production processes performed by animal cell cultures, as it describes the cell growth and reflects the cell physiological state. When there are changes in these parameters, which are indicated by variations ofµ, the synthesis and the quality of antibodies are often affected. Therefore, it is essential to monitor and control the variations ofµto assure the antibody production and achieve high product quality. In this study, a novel approach for on‐line estimation ofµwas developed based on the process analytical technology initiative by using an in situ dielectric spectroscopy. Critical moments, such as significantµdecreases, were successfully detected by this method, in association with changes in cell physiology as well as with an accumulation of nonglycosylated antibodies. Thus, this method was used to perform medium renewals at the appropriate time points, maintaining the values ofµclose to its maximum. Using this method, we demonstrated that the physiological state of cells remained stable, the quantity and the glycosylation quality of antibodies were assured at the same time, leading to better process performances compared with the reference feed‐harvest cell cultures carried out by using off‐line nutrient measurements.
Combining orthogonal CRISPR and CRISPRi systems for genome engineering and metabolic pathway modulation in Escherichia coli
Authors: Sung Li‐Yu , Wu Meng‐Ying , Lin Mei‐Wei , Hsu Mu‐Nung , Truong Vu Anh , Shen Chih‐Che , Tu Yi , Hwang Kuen‐Yuan , Tu An‐Pang , Chang Yu‐Han , Hu Yu‐Chen 
Published: January 2019

AbstractCRISPR utilizing Cas9 from Streptococcus pyogenes (SpCas9) and CRISPR interference (CRISPRi) employing catalytically inactive SpCas9 (SpdCas9) have gained popularity for
Escherichia coli engineering. To integrate the SpdCas9‐based CRISPRi module using CRISPR while avoiding mutual interference between SpCas9/SpdCas9 and their cognate single‐guide RNA (sgRNA), this study aimed at exploring an alternative Cas nuclease orthogonal to SpCas9. We compared several Cas9 variants from different microorganisms such as
Staphylococcus aureus (SaCas9) and
Streptococcus thermophilius CRISPR1 (St1Cas9) as well as Cas12a derived from
Francisella novicida (FnCas12a). At the commonly used
E. coli model genes
LacZ, we found that SaCas9 and St1Cas9 induced DNA cleavage more effectively than FnCas12a. Both St1Cas9 and SaCas9 were orthogonal to SpCas9 and the induced DNA cleavage promoted the integration of heterologous DNA of up to 10 kb, at which size St1Cas9 was superior to SaCas9 in recombination frequency/accuracy. We harnessed the St1Cas9 system to integrate SpdCas9 and sgRNA arrays for constitutive knockdown of three genes, knock‐in
pyc and knockout
adhE, without compromising the CRISPRi knockdown efficiency. The combination of orthogonal CRISPR/CRISPRi for metabolic engineering enhanced succinate production while inhibiting byproduct formation and may pave a new avenue to
E. coli engineering.
Three‐dimensional spherical gelatin bubble‐based scaffold improves the myotube formation of H9c2 myoblasts
Authors: Mei Chieh , Chao Chih‐Wei , Lin Che‐Wei , Li Shing Tak , Wu Kuan‐Han , Yang Kai‐Chiang , Yu Jiashing 
Published: January 2019

AbstractMicroenvironmental factors including physical and chemical cues can regulate stem cells as well as terminally differentiated cells to modulate their biological function and differentiation. However, one of the physical cues, the substrate's dimensionality, has not been studied extensively. In this study, the ﬂow‐focusing method with a microﬂuidic device was used to generate gelatin bubbles to fabricate highly ordered three‐dimensional (3D) scaffolds. Rat H9c2 myoblasts were seeded into the 3D gelatin bubble‐based scaffolds and compared to those grown on 2D gelatin‐coating substrates to demonstrate the influences of spatial cues on cell behaviors. Relative to cells on the 2D substrates, the H9c2 myoblasts were featured by a good survival and normal mitochondrial activity but slower cell proliferation within the 3D scaffolds. The cortical actin filaments of H9c2 cells were localized close to the cell membrane when cultured on the 2D substrates, while the F‐actins distributed uniformly and occupied most of the cell cytoplasm within the 3D scaffolds. H9c2 myoblasts fused as multinuclear myotubes within the 3D scaffolds without any induction but cells cultured on the 2D substrates had a relatively lower fusion index even differentiation medium was provided. Although there was no difference in actin α 1 and myosin heavy chain 1, H9c2 cells had a higher myogenin messenger RNA level in the 3D scaffolds than those of on the 2D substrates. This study reveals that the dimensionality influences differentiation and fusion of myoblasts.
Distinct timescales of RNA regulators enable the construction of a genetic pulse generator
Authors: Westbrook Alexandra , Tang Xun , Marshall Ryan , Maxwell Colin S. , Chappell James , Agrawal Deepak K. , Dunlop Mary J. , Noireaux Vincent , Beisel Chase L. , Lucks Julius , Franco Elisa 
Published: January 2019

AbstractTo build complex genetic networks with predictable behaviors, synthetic biologists use libraries of modular parts that can be characterized in isolation and assembled together to create programmable higher‐order functions. Characterization experiments and computational models for gene regulatory parts operating in isolation are routinely used to predict the dynamics of interconnected parts and guide the construction of new synthetic devices. Here, we individually characterize two modes of RNA‐based transcriptional regulation, using small transcription activating RNAs (STARs) and clustered regularly interspaced short palindromic repeats interference (CRISPRi), and show how their distinct regulatory timescales can be used to engineer a composed feedforward loop that creates a pulse of gene expression. We use a cell‐free transcription‐translation system (TXTL) to rapidly characterize the system, and we apply Bayesian inference to extract kinetic parameters for an ordinary differential equation‐based mechanistic model. We then demonstrate in simulation and verify with TXTL experiments that the simultaneous regulation of a single gene target with STARs and CRISPRi leads to a pulse of gene expression. Our results suggest the modularity of the two regulators in an integrated genetic circuit, and we anticipate that construction and modeling frameworks that can leverage this modularity will become increasingly important as synthetic circuits increase in complexity.
In vitro vascularized liver and tumor tissue microenvironments on a chip for dynamic determination of nanoparticle transport and toxicity
Authors: Ozkan Alican , Ghousifam Neda , Hoopes Paul Jack , Yankeelov Thomas Edward , Rylander Marissa Nichole 
Published: January 2019

AbstractThis paper presents the development of a vascularized breast tumor and healthy or tumorigenic liver microenvironments‐on‐a‐chip connected in series. This is the first description of a vascularized multi tissue‐on‐a‐chip microenvironment for modeling cancerous breast and cancerous/healthy liver microenvironments, to allow for the study of dynamic and spatial transport of particles. This device enables the dynamic determination of vessel permeability, the measurement of drug and nanoparticle transport, and the assessment of the associated efficacy and toxicity to the liver. The platform is utilized to determine the effect of particle size on the spatiotemporal diffusion of particles through each microenvironment, both independently and in response to the circulation of particles in varying sequences of microenvironments. The results show that when breast cancer cells were cultured in the microenvironments they had a 2.62‐fold higher vessel porosity relative to vessels within healthy liver microenvironments. Hence, the permeability of the tumor microenvironment increased by 2.35‐ and 2.77‐fold compared with a healthy liver for small and large particles, respectively. The extracellular matrix accumulation rate of larger particles was 2.57‐fold lower than smaller particles in a healthy liver. However, the accumulation rate was 5.57‐fold greater in the breast tumor microenvironment. These results are in agreement with comparable in vivo studies. Ultimately, the platform could be utilized to determine the impact of the tissue or tumor microenvironment, or drug and nanoparticle properties, on transport, efficacy, selectivity, and toxicity in a dynamic, and high‐throughput manner for use in treatment optimization.
Analysis of Golgi pH in Chinese hamster ovary cells using ratiometric pH‐sensitive fluorescent proteins
Authors: Lee Jong Hyun , Kim Jihoon , Park Jong‐Ho , Heo Won Do , Lee Gyun Min 
Published: January 2019

AbstractAcidic Golgi pH plays an important role in protein glycosylation, one of the critical quality attributes of therapeutic proteins. To determine the intracellular Golgi pH during culture, stable Chinese hamster ovary (CHO) cell clones expressing pHluorin2, a ratiometric pH‐sensitive fluorescent protein (FP), in the cis‐ and trans‐Golgi, were constructed by fusing pHluorin2 with specific targeting proteins, acetylglucosaminyltransferase, and a galactosyltransferase, respectively. Stable CHO cell clones expressing pHluorin2 in the cytoplasm were also constructed. The subcellular localization of FPs was confirmed by immunofluorescence analysis. Live‐cell imaging revealed that the intracellular pH (pHi) of clones expressing the ratiometric pH‐sensitive FPs converged to a specific pH range (cis‐Golgi: 6.4–6.5; trans‐Golgi: 5.9–6.0; and cytoplasm: 7.1–7.2). The pHi was successfully evaluated in various culture conditions. Although culture pH was maintained at 7.2 in a bioreactor, the Golgi pH increased with culture time. Elevated ammonia concentration and osmolality were partially responsible for the increased Golgi pH during bioreactor cultures. Taken together, the application of ratiometric pH‐sensitive FPs in monitoring the Golgi pH of CHO cells during culture provides a new perspective to improve protein glycosylation through pHi control.
Continuous integrated antibody precipitation with two‐stage tangential flow microfiltration enables constant mass flow
Authors: Burgstaller Daniel , Jungbauer Alois , Satzer Peter 
Published: January 2019

AbstractContinuous precipitation is a new unit operation for the continuous capture of antibodies. The capture step is based on continuous precipitation with PEG6000 and Zn++ in a tubular reactor integrated with a two‐stage continuous tangential flow filtration unit. The precipitate cannot be separated with centrifugation, because a highly compressed sediment results in poor resolubilization. We developed a new two‐stage tangential flow microfiltration method, where part of the concentrated retentate of the first stage was directly fed to the second stage, together with the wash buffer. Thus, the precipitate was concentrated and washed in a continuous process. We obtained 97% antibody purity, a 95% process yield during continuous operation, and a fivefold reduction in pre‐existing high‐molecular‐weight impurities. For other unit operations, surge tanks are often required, due to interruptions in the product mass flow out of the unit operation (e.g., the bind/elute mode in periodic counter‐current chromatography). Our setup required no surge tanks; thus, it provided a truly continuous antibody capture operation with uninterrupted product mass flow. Continuous virus inactivation and other flow‐through unit operations can be readily integrated downstream of the capture step to create truly continuous, integrated, downstream antibody processing without the need for hold tanks.
Effect of precise control of flux ratio between the glycolytic pathways on mevalonate production in Escherichia coli
Authors: Kamata Kentaro , Toya Yoshihiro , Shimizu Hiroshi 
Published: January 2019

AbstractMevalonate is a useful metabolite synthesized from three molecules of acetyl‐CoA, consuming two molecules of NADPH. Escherichia coli (
E. coli) catabolizes glucose to acetyl‐CoA via several routes, such as the Embden–Meyerhof–Parnas (EMP) and the oxidative pentose phosphate (oxPP) pathways. Although the oxPP pathway supplies NADPH, it is disadvantageous in terms of acetyl‐CoA supply, compared with the EMP pathway. In this study, the optimal flux ratio between the EMP and oxPP pathways on the mevalonate yield was investigated. Expression level of
pgi was controlled by isopropyl β‐D‐1‐thiogalactopyranoside (IPTG) inducible promoter in an engineered mevalonate‐producing
E. coli strain. The relationship between the flux ratio and mevalonate yield was evaluated by changing the flux ratio by varying IPTG concentration. At the stationary phase, the mevalonate yield was maximum at an EMP flux of 39.7%, and was increased by 25% compared with that with no flux control (EMP flux of 70.4%). The optimal flux ratio was consistent with the theoretical value based on the mass balance of NADPH. The flux ratio between EMP and oxPP pathways affects the synthesis fluxes of mevalonate and acetate from acetyl‐CoA. Fine tuning of the flux ratio would be necessary to achieve an optimized production of metabolites that require NADPH.
Altered functional connectivity in binge eating disorder and bulimia nervosa: A resting‐state fMRI study
Authors: Stopyra Marion A. , Simon Joe J. , Skunde Mandy , Walther Stephan , Bendszus Martin , Herzog Wolfgang , Friederich Hans‐Christoph 
Published: January 2019

AbstractIntroductionThe etiology of bulimic‐type eating (BTE) disorders such as binge eating disorder (BED) and bulimia nervosa (BN) is still largely unknown. Brain networks subserving the processing of rewards, emotions, and cognitive control seem to play a crucial role in the development and maintenance of eating disorders. Therefore, further investigations into the neurobiological underpinnings are needed to discern abnormal connectivity patterns in BTE disorders.MethodsThe present study aimed to investigate functional as well as seed‐based connectivity within well‐defined brain networks. Twenty‐seven individuals with BED, 29 individuals with BN, 28 overweight, and 30 normal‐weight control participants matched by age, gender, and education underwent resting‐state functional magnetic resonance imaging. Functional connectivity was assessed by spatial group independent component analysis and a seed‐based correlation approach by examining the default mode network (DMN), salience network (SN), and executive network (EN).ResultsGroup comparisons revealed that BTE disorder patients exhibit aberrant functional connectivity in the dorsal anterior cingulate cortex (dACC) within the SN, as well as in the medial prefrontal cortex within the DMN. Furthermore, BED and BN groups differed from each other in functional connectivity within each network. Seed‐based correlational analysis revealed stronger synchronous dACC‐retrosplenial cortex activity in the BN group.ConclusionOur findings demonstrate abnormalities in brain networks involved in salience attribution, self‐referential processing, and cognitive control in bulimic‐type eating disorders. Together with our observation of functional connectivity differences between BED and BN, this study offers a differentiated account of both similarities and differences regarding brain connectivity in BED and BN.
Fecal Fusobacterium nucleatum for the diagnosis of colorectal tumor: A systematic review and meta‐analysis
Authors: Zhang Xinyu , Zhu Xiaoqiang , Cao Yingying , Fang Jing‐Yuan , Hong Jie , Chen Haoyan 
Published: January 2019

AbstractThe fecal Fusobacterium nucleatum has been reported as a potential noninvasive biomarker for colorectal tumor in several studies, but its exact diagnostic accuracy was ambiguous due to the wide range of sensitivity and specificity. To assess the diagnostic accuracy of fecal F. nucleatum for colorectal tumor, we searched electronic databases including PubMed, Cochrane Library, Embase, and Web of Science, without any date and language restrictions. Two reviewers independently extracted data and appraised study quality with Quality Assessment of Diagnostic Accuracy Studies. We included ten studies comprising 13 cohorts for colorectal cancer (CRC) and seven cohorts for colorectal adenoma (CRA). A total of 1450 patients and 1421 controls for CRC and 656 patients and 827 controls for CRA were included. The pooled sensitivity and specificity of fecal F. nucleatum for CRC were 71% (95% CI, 61%‐79%) and 76% (95% CI, 66%‐84%), with the area under the receiver‐operating characteristics (AUC) curve of 0.80 (95% CI, 0.76‐0.83). The pooled sensitivity and specificity of fecal F. nucleatum for CRA were 36% (95% CI, 27%‐46%) and 73% (95% CI, 65%‐79%), with an AUC of 0.60 (95% CI, 0.56‐0.65). Substantial heterogeneity among studies existed, which was partly caused by DNA extraction kits, regions of study, sample size, and demographic characteristics of participants. Fecal F. nucleatum was valuable for the diagnosis of CRC although it performed below expectation. For CRA, the specificity of fecal F. nucleatum indicated the possibility of noninvasive screening. Subgroup analyses for adenoma were incomplete due to lack of data. Heterogeneity limited the credibility of the study.