bluuebunny/crossref_metadata_2025 huggingface dataset:
Donor Promiscuity of a Thermostable Transketolase by Directed Evolution: Efficient Complementation of 1‐Deoxy‐d‐xylulose‐5‐phosphate Synthase Activity
Authors: Saravanan Thangavelu , Junker Sebastian , Kickstein Michael , Hein Sascha , Link Marie‐Kristin , Ranglack Jan , Witt Samantha , Lorillière Marion , Hecquet Laurence , Fessner Wolf‐Dieter
Published: April 2017

Enzymes catalyzing asymmetric carboligation reactions typically show very high substrate specificity for their nucleophilic donor substrate components. Structure‐guided engineering of the thermostable transketolase from Geobacillus stearothermophilus by directed in vitro evolution yielded new enzyme variants that are able to utilize pyruvate and higher aliphatic homologues as nucleophilic components for acyl transfer instead of the natural polyhydroxylated ketose phosphates or hydroxypyruvate. The single mutant H102T proved the best hit toward 3‐methyl‐2‐oxobutyrate as donor, while the double variant H102L/H474S showed highest catalytic efficiency toward pyruvate as donor. The latter variant was able to complement the auxotrophic deficiency of Escherichia coli cells arising from a deletion of the dxs gene, which encodes for activity of the first committed step into the terpenoid biosynthesis, offering the chance to employ a growth selection test for further enzyme optimization.
Influence of shear thinning and material flow on robotic dispensing of poly(ethylene glycol) diacrylate/poloxamer 407 hydrogels
Authors: Kraut Gabriele , Yenchesky Laura , Prieto Fermin , Tovar Günter E. M. , Southan Alexander
Published: April 2017

Robotic dispensing of hydrogels offers a direct way for generating complex hydrogel shapes. For this, there is a general need for hydrogel formulations with suitable rheological properties. In this contribution, hydrogel formulations containing poly(ethylene glycol) diacrylate (PEG‐DA) and Poloxamer 407 are characterized regarding their flow behavior during robotic dispensing. Formulations contain between 15% and 20% PEG‐DA and 22.5% and 25% Poloxamer 407. All formulations show shear thinning which can be described using a power law with a power law index between 0.10 and 0.11 and calculated shear rates at the wall of the dispensing needle of 379 s−1with a dispensing speed of 8 mm s−1and a dispensing needle inner diameter of 0.51 mm. Thus, facilitating the generation of smooth hydrogel strands, three‐dimensional hydrogel objects can be prepared without flow after robotic dispensing and can be cured afterward to elastic hydrogels, retaining the shape of the dispensed object. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2017,134, 45083.
An environmentally friendly clay‐based polymer composite “paper”
Authors: Liang Wei‐Dong , Qian Chen , Zhu Zhao‐Qi , Sun Han‐Xue , Ma Chong‐Hua , Wang Li‐Na , Wang Ran , Li An
Published: April 2017

The paper industry is closely related to our daily life. Vast quantities of paper requirement worldwide lead to astonishing lumber consumption and environmental pollution. So the exploration of alternative paper‐like material should be of great importance. Here, we reported the preparation of a kind of environmentally friendly clay‐based polymer composite paper‐like film by incorporation of a kind of nanometer sized natural clay crystals, in this case attapulgite (ATP), into degradable poly(vinyl alcohol) (PVA) only though a simple blending and subsequently casting method. X‐ray analysis shows that no changes in the crystalline structure of ATP were observed in the PVA matrix. Even with a high content of clay crystals in composites (50 wt %), the resulting ATP‐PVA composite films (named as APCF) show excellent flexibility and tensile strength up to 22.19 MPa. The doping of ATP also results in flame retardant of composites, making it ideal candidate for packing and also building decoration applications. Interestingly, the APCF are printable and also much tough and tensile. Due to the simple fabrication, nearly no pollution emission process and easily to be scaled up, the APCF have great potentials as a kind of alternative for paper materials for diverse applications. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45128.
Sonochemical synthesis and stabilization of concentrated antimicrobial silver‐chitosan nanoparticle dispersions
Authors: Francesko Antonio , Cano Fossas Marta , Petkova Petya , Fernandes Margarida M. , Mendoza Ernest , Tzanov Tzanko
Published: April 2017

This work reports on a green synthetic route to produce concentrated aqueous dispersions of silver nanoparticles (AgNP) employing high‐intensity ultrasound (US) and chitosan (CS) as a nontoxic reducing agent for Ag+ salts and AgNP stabilizer. The sonication simultaneously boosted the synthesis and improved the stability of the AgNP, capping them with CS. Hybrid AgNP‐CS antimicrobial dispersions, stable for at least 6 months, were synthesized in a simple single step process. The use of US allowed for applying relatively mild processing temperatures (60 °C) and reaction time between 30 min and 3 h to obtain concentrated dispersions of AgNP that otherwise could not be obtained even after 72 h under mechanical stirring at the same reaction conditions. Upon sonication spherical AgNP‐CS with a size between 60 and 100 nm were generated, in contrast to the average diameter of ∼200 nm of the particles obtained by stirring. The antibacterial efficiency of the AgNP‐CS hybrids was evaluated against the medically relevant pathogens Staphylococcus aureus and Escherichia coli. The US‐synthesized AgNP‐CS showed more than three fold higher antibacterial activity compared to the particles obtained under stirring, due to their higher concentration and smaller size. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45136.
A large‐scale double‐stage‐screw 3D printer for fused deposition of plastic pellets
Authors: Liu Xiaojun , Chi Baihong , Jiao Zhiwei , Tan Jing , Liu Fengfeng , Yang Weimin
Published: April 2017

Fused deposition molding (FDM) is the most popular technology in the fields of three‐dimensional printing, but it is hard to use a variety of plastic materials due to the limitation of filament form of material. Using plastic pellets as printing materials gives advantages in cost, processing speed, and available materials. In this work, a large‐scale double‐screw FDM three‐dimensional printer based on plastic pellets has been designed. It is capable of printing large plastic products at a low cost and high speed. Using ABS + 10%GF as printing material, this work is first focused on the effects of the pressure and speed of the metering screw on the flowrate of melt. The equation for the relationship of these three parameters was established as well. Based on this equation, the effects of melt flow, printing speed, and layer thickness on the width of fused filament were investigated with experiments. Furthermore, the effects of printing spacing between fused filaments on surface accuracy and bonding strength were also explored. By printing models, it was revealed that the designed printer is able to print products with plastic pellets. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45147.
Synthesis and Structure–Activity Relationships of Novel Benzylamine‐Type Antifungals as Butenafine‐Related Antimycotics
Authors: Krauss Jürgen , Stadler Martina , Bracher Franz
Published: April 2017

Benzylamine‐type antimycotics like naftifine, butenafine, or terbinafine are a well‐known class of antimycotics since the 1980s. The following paper describes the synthesis and biological evaluation of a series of novel benzylamine‐type antimycotics characterized by an isooctyl side chain and various substituents at the benzylamine moiety. The compounds were prepared from benzaldehyde derivatives and 2‐amino‐6‐methylheptane by reductive amination with sodium triacetoxyborohydride and subsequent precipitation with hydrogen chloride. The antimycotic activity of the resulting compounds was evaluated in an agar diffusion assay against the yeasts C. glabrata and Yarrowia lipolytica, the mold Aspergillus niger and the dermatophyte H. burtonii. The compounds were also tested in a microdilution assay against the yeast Candida glabrata and the dermatophyte H. burtonii to determine the minimal inhibitory concentrations (MIC). Compounds with an aromatic ether side chain or a short alkyl ether side chain showed significant antimycotic activity against C. glabrata, comparable to terbinafine or clotrimazole.
Chemogenetic Inhibition of Pain Neurons in a Mouse Model of Osteoarthritis
Authors: Miller Rachel E. , Ishihara Shingo , Bhattacharyya Bula , Delaney Ada , Menichella Daniela M. , Miller Richard J. , Malfait Anne‐Marie
Published: April 2017

Objective

To determine the ability of drugs that activate inhibitory G protein–coupled receptors (GPCRs) expressed in peripheral voltage‐gated sodium channel 1.8 (NaV1.8)–positive sensory neurons to control osteoarthritis (OA)–associated pain.

Methods

We used designer receptors exclusively activated by a designer drug (DREADD) technology, which employs engineered GPCRs to activate or inhibit neurons upon binding the synthetic ligand clozapine N‐oxide (CNO). NaV1.8‐Pdi C57BL/6 mice were generated to express the inhibitory DREADD receptor Pdi in NaV1.8‐expressing sensory neurons. Destabilization of the medial meniscus (DMM) surgery was performed in 10‐week‐old male mice. Four, 8, 12, or 16 weeks after surgery, knee hyperalgesia or hind paw mechanical allodynia was tested. Subsequently, CNO or vehicle was administered, and the effect on pain‐related behaviors was measured by a blinded observer. Morphine was used as a control.

Results

Immunohistochemistry and electrophysiology confirmed functional expression of the inhibitory DREADD receptor Pdi by NaV1.8‐positive sensory neurons. Acute inhibition of NaV1.8‐expressing neurons in mice treated with CNO reduced knee hyperalgesia 4 weeks after DMM surgery and reduced mechanical allodynia 8 weeks after DMM surgery. Inhibition had no effect on pain‐related behaviors 12 and 16 weeks after DMM surgery. Morphine, a drug that activates GPCRs in the peripheral and central nervous systems, was still effective in the later stage of experimental OA.

Conclusion

Chemogenetic inhibition of NaV1.8‐expressing neurons blocks knee hyperalgesia and mechanical allodynia in early experimental OA, but is no longer efficacious in the later stages. These data indicate that activation of inhibitory GPCRs located solely outside the central nervous system may be ineffective in treating chronic OA pain.
Highly Efficient, Green, and Scalable β‐Cyclodextrin‐Assisted Aqueous Exfoliation of Transition‐Metal Dichalcogenides: MoS2 and ReS2 Nanoflakes
Authors: Zhao Wancheng , Tan Xingxing , Jiang Jingyun , Liu Feijie , Mu Tiancheng
Published: April 2017

The β‐cyclodextrin‐assisted aqueous‐exfoliation method was used to prepare transition‐metal dichalcogenide (TMD) nanosheets, in a cheap, highly efficient, scalable and environmentally friendly manner. As study cases, MoS2 and ReS2 nanoflakes were prepared according to this method. Particularly, the effective exfoliation of ReS2 crystals in an aqueous environment was observed for the first time. Moreover, exfoliated nanomaterials can be readily utilized in hydrogen evolution reactions (HERs) as noble‐metal‐free catalysts. This work provides new opportunities for highly efficient exfoliation of TMDs and other 2D nanomaterials into few‐layer nanosheets in aqueous media. Their production process showed high biocompatibility, broad applicability and excellent sustainability.
Synchronization Control for a Swarm of Unicycle Robots: Analysis of Different Controller Topologies
Authors: Gutiérrez H. , Morales A. , Nijmeijer H.
Published: April 2017

This paper proposes a nonlinear synchronization controller for a swarm of unicycle robots performing a cooperative task, i.e., following a desired trajectory per robot while maintaining a prescribed formation. The effect of communication between robots is analyzed and several network topologies are investigated, e.g., all‐to‐all, ring type, undirected, among others. The stability analysis of the closed loop system is provided using the Lyapunov method. Experiments with four unicycle robots are presented to validate the control law and communication analysis. Accumulated errors over the experiment time are presented in order to determine which topology is most efficient.
A dynamical evolution study of 40 2MASS open clusters
Authors: Güneş Orhan , Karataş Yüksel , Bonatto Charles
Published: April 2017

We investigate the dynamical evolution of 40 open clusters (OCs) by means of their astrophysical parameters derived from field‐decontaminated 2MASS photometry. We find a bifurcation in the planes' core radius versus age and cluster radius versus age, in which part of the clusters appear to expand with time probably due to the presence of stellar black holes while others seem to shrink due to dynamical relaxation.

Mass functions (MFs) are built for three‐fourth of the sample (31 OCs), which are used to search for indications of mass segregation and external dynamical processes by means of relations between astrophysical, structural, and evolutionary parameters. We detect a flattening of MF slopes occurring at the evolutionary parameters τcore ≤ 32 and τoverall ≤ 30, respectively.

Within the uncertainties involved, the overall MF slopes of 14 out of 31 OCs with moverall > 500 M⊙ are consistent with Kroupa's initial mass function, implying little, or no dynamical evolution for these clusters. The remaining 17 OCs with MF slopes departing from that of Kroupa show mild/large‐scale mass segregation due to dynamical evolution.
Cosmology with AGN: can we use quasars as standard candles?
Authors: Risaliti G. , Lusso E.
Published: April 2017

The nonlinear relation between X‐ray and UV luminosity in quasars can be used to estimate their distance. Recently, we have shown that, despite the large dispersion of the relation, a Hubble diagram made of large samples of quasars can provide unique constraints on cosmology at high redshift. Furthermore, the dispersion of the relation is heavily affected by measurement errors: until now we have used serendipitous X‐ray observations, but dedicated observations would significantly increase the precision of the distance estimates. We discuss the future role of XMM in this new field, showing (a) the fundamental contribution of the Serendipitous Source Catalog and of large surveys and (b) the breakthrough advancements we may achieve with the observation of a large number of Sloan Digital Sky Survey (SDSS) quasars at high redshift: every ∼10 quasars observed at z∼3 would be equivalent to discovering a supernova at that redshift.
Pharmacokinetic analysis of inhaled salmeterol in asthma patients: Evidence from two dry powder inhalers
Authors: Soulele Konstantina , Macheras Panos , Karalis Vangelis
Published: April 2017

Salmeterol (SAL) is a long‐acting β2‐adrenergic agonist, which is widely used in the therapy of asthma. The aim of this study was to investigate the pharmacokinetics (PK) of inhaled salmeterol in asthma patients using two different dry powder inhalers. This analysis was based on data from 45 subjects who participated in a two‐sequence, four‐period crossover bioequivalence (BE) study after single administration of the test (T) and reference (R) products. In order to mimic more closely the real treatment conditions, activated charcoal was not co‐administered. Plasma concentration–time (C–t) data were initially analysed using classic non‐compartmental PK approaches, while the main objective of the study was to apply population PK modeling. The relative fraction of the dose absorbed via the lungs (RL) was set as a parameter in the structural model. The plasma C–t profiles of salmeterol showed a biphasic time course indicating a parallel pulmonary and gastrointestinal (GI) absorption. A two‐compartment disposition model with first order absorption from the GI and very rapid absorption from lungs (like an i.v. bolus) was found to describe successfully the C–t profiles of salmeterol. The estimated RL value was 13% suggesting a high gut deposition of inhaled salmeterol. Women were found to exert less capability to eliminate salmeterol than men, while body weight (in allometric form) was found to be an important covariate on the peripheral volume of distribution.
Einfluss der Stahlfaserzugabe auf die Spannungs‐Dehnungs‐Linie von Beton unter Druckbeanspruchung
Authors: Müller Corinna
Published: April 2017

Aus zahlreichen Forschungsarbeiten ist bekannt, dass sich durch die Zugabe von Stahlfasern die Verformungseigenschaften und der Bruchmechanismus von Beton unter Druckbeanspruchung beeinflussen lassen (u. a. [1–3]). Um zukünftig die Eigenschaften von Stahlfaserbeton bei der Entwicklung robuster druckbeanspruchter Stahlbetonbauteile berücksichtigen zu können, ist ein Ansatz zur Beschreibung der Spannungs‐Dehnungs‐Linie von Stahlfaserbeton erforderlich. Am iBMB der Technischen Universität Braunschweig wurden experimentelle Untersuchungen durchgeführt, auf Basis derer ein für die praxisüblichen Stahlfasertypen geeigneter Ansatz zur Beschreibung der Spannungs‐Dehnungs‐Linie von Stahlfaserbeton unter Druckbeanspruchung entwickelt worden ist. Der neuartige Ansatz berücksichtigt die Stahlfasertragwirkung über materialspezifische Kennwerte in Anlehnung an die DAfStb‐Richtlinie „Stahlfaserbeton” [4].
Bemessung von Industrieböden aus Beton
Authors: Schwabach Enrico
Published: April 2017

Der Deutsche Beton‐ und Bautechnik‐Verein E.V. (DBV) hat sein Merkblatt „Industrieböden aus Beton für Frei‐ und Hallenflächen” aus dem Jahre 2004 komplett überarbeitet und ergänzt. Das neue Merkblatt „Industrieböden aus Beton” (Fassung Februar 2017) behandelt die Besonderheiten von Industrieböden aus Beton für Hallen‐ und Freiflächen bei Entwurf, Bemessung und Konstruktion sowie der Ausführung. Es wartet beispielsweise mit wesentlichen Neuerungen im Hinblick auf die Bemessung mit reduzierten Teilsicherheitsbeiwerten bzw. das Sicherheitskonzept für nicht tragende und nicht aussteifende Industrieböden auf. Zudem werden sogenannte Entwurfsgrundsätze eingeführt, wie mit der Rissbildung bei Industrieböden umgegangen werden sollte. Die im Merkblatt empfohlenen Regeln sollen allen am Bau Beteiligten, dem Planer, dem Bauausführenden und auch dem Bauherrn eine Hilfe sein, um Industrieböden so zu planen und herzustellen, dass der Bedarf des Bauherrn bzw. des Nutzers im Rahmen der technischen Machbarkeit und der Wirtschaftlichkeit erfüllt wird. Im vorliegenden Beitrag werden einige Neuerungen hinsichtlich der Bemessungs‐ und Konstruktionsregeln für nicht tragende und nicht aussteifende Industrieböden aus Beton vorgestellt.
Evaluating the efficacy of the Headsprout© reading program with children who have spent time in care
Authors: Storey Catherine , McDowell Claire , Leslie Julian C.
Published: April 2017

This study investigated whether Headsprout©, an internet‐based phonics program designed on behavioral principles, is an effective supplementary tool to improve literacy skills of children who have spent time in care and are at risk of reading failure. Participants were 8 children (aged 5 to 10) who had spent over 3 years in care and were fully adopted at the time of the study. Participants' literacy skills were assessed prior to intervention using 2 standardized reading attainment tests. Participants were then randomly assigned to either treatment or a waiting list comparison group. There were 2 Headsprout© treatments, but all participants in the treatment group completed 1 HeadsproutStartCopTextStartCopText© lesson 4 times per week, under the supervision of the first author, while participants in the comparison group interacted with the first author 4 times per week engaging in nonliteracy‐based computer activities. Results from 2 standardized reading attainment tests showed an improvement in word recognition age and oral reading fluency for the HeadsproutStartCopTextStartCopText© learners but scores either remained the same or decreased over a 4‐month period for participants in the comparison group. The findings support the wider use of HeadsproutStartCopTextStartCopText© with at‐risk children though more research is clearly warranted at this time.
Binding of fluphenazine with human serum albumin in the presence of rutin and quercetin: An evaluation of food‐drug interaction by spectroscopic techniques
Authors: Jing Jiao‐Jiao , Liu Bin , Wang Xin , Wang Xin , He Ling‐Ling , Guo Xue‐Yuan , Xu Ming‐Ling , Li Qian‐Yu , Gao Bo , Dong Bo‐Yang
Published: April 2017

The interactions between human serum albumin (HSA) and fluphenazine (FPZ) in the presence or absence of rutin or quercetin were studied by fluorescence, absorption and circular dichroism (CD) spectroscopy and molecular modeling. The results showed that the fluorescence quenching mechanism was static quenching by the formation of an HSA–FPZ complex. Entropy change (ΔS0) and enthalpy change (ΔH0) values were 68.42 J/(mol⋅K) and −4.637 kJ/mol, respectively, which indicated that hydrophobic interactions and hydrogen bonds played major roles in the acting forces. The interaction process was spontaneous because the Gibbs free energy change (ΔG0) values were negative. The results of competitive experiments demonstrated that FPZ was mainly located within HSA site I (sub‐domain IIA). Molecular docking results were in agreement with the experimental conclusions of the thermodynamic parameters and competition experiments. Competitive binding to HSA between flavonoids and FPZ decreased the association constants and increased the binding distances of FPZ binding to HSA. The results of absorption, synchronous fluorescence, three‐dimensional fluorescence, and CD spectra showed that the binding of FPZ to HSA caused conformational changes in HSA and simultaneous effects of FPZ and flavonoids induced further HSA conformational changes.
Genetic engineering of the branched fatty acid metabolic pathway of Bacillus subtilis for the overproduction of surfactin C14 isoform
Authors: Dhali Debarun , Coutte François , Arias Anthony Argüelles , Auger Sandrine , Bidnenko Vladimir , Chataigné Gabrielle , Lalk Michael , Niehren Joachim , de Sousa Joana , Versari Cristian , Jacques Philippe
Published: April 2017

Surfactin, a lipopeptide produced by Bacillus subtilis, is one of the most powerful biosurfactants known. This molecule consists of a cyclic heptapeptide linked to a β‐hydroxy fatty acid chain. The isomery and the length of the fatty acid (FA) chain are responsible for the surfactin's activities. In this study, the gene codY, which encode for the global transcriptional regulator and the gene lpdV, located in the bkd operon (lpdV, bkdAA, bkdAB and bkdB genes), which is responsible for the last step of the branched chain amino acid (BCAA) degradation in acyl‐CoA were deleted. The influence of these deletions on the quantitative and qualitative surfactin production was analysed. The surfactin production was quantified by RP‐HPLC and the surfactin isoforms were characterized using LC‐MS‐MS and GC‐MS analysis. The results obtained in the mutants showed an enhancement of surfactin specific production by a factor of 5.8 for the codY mutant and 1.4 for lpdV mutant. Moreover qualitative analysis of the lpdV mutant reveals that it mainly produced surfactin C14 isoform (2 fold more than the wild type) with linear FA chain. Complete analysis of the extracellular metabolites using 1H quantitative NMR reveals a reduced production of acetoin in this mutant. This work demonstrates for the first time an original approach to overproduce specifically surfactin with C14 FA chain.
Population-based study demonstrating an increase in colorectal cancer in young patients
Authors: Gandhi J , Davidson C , Hall C , Pearson J , Eglinton T , Wakeman C , Frizelle F
Published: April 2017

Background

New Zealand has among the highest rates of colorectal cancer in the world and is an unscreened population. The aim of this study was to determine the trends in incidence and tumour location in the New Zealand population before the introduction of national colorectal cancer screening.

Methods

Data were obtained from the national cancer registry and linked to population data from 1995 to 2012. Incidence rates for colorectal cancer by sex, age (less than 50 years, 50–79 years, 80 years or more) and location (proximal colon, distal colon and rectum) were assessed by linear regression.

Results

Among patients aged under 50 years, the incidence of distal colonic cancer in men increased by 14 per cent per decade (incidence rate ratio (IRR 1·14), 95 per cent c.i. 1·00 to 1·30; P = 0·042); the incidence of rectal cancer in men increased by 18 per cent (IRR 1·18, 1·06 to 1·32; P = 0·002) and that in women by 13 per cent (IRR 1·13, 1·02 to 1·26; P = 0·023). In those aged 50–79 years, there was a reduction in incidence per decade of proximal, distal and rectal cancers in both sexes. In the group aged 80 years and over, proximal cancer incidence per decade increased by 19 per cent in women (IRR 1·19, 1·13 to 1·26; P < 0·001) and by 25 per cent in men (IRR 1·25, 1·18 to 1·32; P < 0·001); among women, the incidence of distal colonic cancer decreased by 8 per cent (IRR 0·92, 0·86 to 0·98); P = 0·012), as did that of rectal cancer (IRR 0·92, 0·86 to 0·97; P = 0·005).

Conclusion

The increasing incidence of rectal cancer among younger patients needs to be considered when implementing screening strategies.
Brachial plexus magnetic resonance imaging differentiates between inflammatory neuropathies and does not predict disease course
Authors: Jongbloed Bas A. , Bos Jeroen W. , Rutgers Dirk , van der Pol Willem Ludo , van den Berg Leonard H.
Published: April 2017

Objective

The main objective of this study was to evaluate the correlation between the distribution of brachial plexus magnetic resonance imaging (MRI) abnormalities and clinical weakness, and to evaluate the value of brachial plexus MRI in predicting disease course and response to treatment in multifocal motor neuropathy (MMN), Lewis‐Sumner syndrome (LSS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Methods

Sixty‐seven patients with an inflammatory neuropathy diagnosed at our tertiary referral center for neuromuscular diseases had undergone bilateral T2‐weighted short tau inversion recovery (STIR) MRI of the brachial plexus. We obtained clinical follow‐up data and scored all MRIs for abnormalities and the symmetry of their distribution.

Results

Brachial plexus MRI abnormalities were detected in 45% of the patients. An abnormal MRI did not predict disease course in terms of patterns of weakness, sensory disturbances or response to treatment. Within the spectrum of radiological abnormalities, asymmetrical clinical syndromes, MMN and LSS were significantly associated with asymmetrical radiological abnormalities, whereas symmetrical abnormalities predominated in CIDP (p < .001, phi 0.791).

Conclusion

T2 STIR brachial plexus MRI abnormalities correspond with the distribution of neurological deficits in inflammatory neuropathies, but do not correlate with specific clinical characteristics, response to treatment or disease course.
Valence and magnitude ambiguity in feedback processing
Authors: Gu Ruolei , Feng Xue , Broster Lucas S. , Yuan Lu , Xu Pengfei , Luo Yue‐jia
Published: April 2017

Background

Outcome feedback which indicates behavioral consequences are crucial for reinforcement learning and environmental adaptation. Nevertheless, outcome information in daily life is often totally or partially ambiguous. Studying how people interpret this kind of information would provide important knowledge about the human evaluative system.

Methods

This study concentrates on the neural processing of partially ambiguous feedback, that is, either its valence or magnitude is unknown to participants. To address this topic, we sequentially presented valence and magnitude information; electroencephalography (EEG) response to each kind of presentation was recorded and analyzed. The event‐related potential components feedback‐related negativity (FRN) and P3 were used as indices of neural activity.

Results

Consistent with previous literature, theFRNelicited by ambiguous valence was not significantly different from that elicited by negative valence. On the other hand, theFRNelicited by ambiguous magnitude was larger than both the large and small magnitude, indicating the motivation to seek unambiguous magnitude information. The P3 elicited by ambiguous valence and ambiguous magnitude was not significantly different from that elicited by negative valence and small magnitude, respectively, indicating the emotional significance of feedback ambiguity. Finally, the aforementioned effects also manifested in the stage of information integration.

Conclusion

These findings indicate both similarities and discrepancies between the processing of valence ambiguity and that of magnitude ambiguity, which may help understand the mechanisms of ambiguous information processing.
Resting state and personality component (BIS/BAS) predict the brain activity (EEG and fNIRS measure) in response to emotional cues
Authors: Balconi Michela , Vanutelli Maria E. , Grippa Elisabetta
Published: April 2017

Introduction

The present study explored the role of resting state and personality component (BIS/BAS measure) on prefrontal cortical responsiveness to emotional cues. Indeed, we supposed that lateralized resting activity (right vs. left) and approach (BAS) versus avoidance (BIS) attitude may explain the successive emotional processing within the prefrontal cortex (PFC) based on the stimulus valence (positive and negative emotional cues).

Methods

Hemodynamic (functional near‐infrared spectroscopy, fNIRS) and electroencephalographic (EEG) measures were considered. The resting and experimental brain activity were registered when subjects (N = 21) viewed emotional positive versus negative stimuli (International Affective Picture System, IAPS). LIReeg and LIRnirs (lateralized Index Response) during resting state, and LIeeg and LInirs during emotional processing were acquired.

Results

A set of regression analyses was applied to the multiple measures. The predictive effect of resting activity and approach/avoidance dichotomy were elucidated. Indeed, more left/right resting activity (for both LIReeg and LIRnirs) predicted the successive more brain left/right response (LIeeg and LInirs) to emotional cues. Second, significant effects were revealed as a function of valence (increased right response to negative stimuli; increased left response to positive stimuli) during emotion processing. Third, higher BAS values explained an increased left cortical activity in resting state and in experimental condition for positive cues. In contrast, higher BIS values marked an increased right activity in resting state and in experimental condition in response to negative cues.

Conclusion

The significance of trait component for both resting and emotional cue processing was discussed at light of the present results.
Low glucose concentrations within typical industrial operating conditions have minimal effect on the transcriptome of recombinant CHO cells
Authors: Gowtham Yogender Kumar , Saski Christopher A. , Harcum Sarah W.
Published: April 2017

Typically, mammalian cell culture medium contains high glucose concentrations that are analogous to diabetic levels in humans, suggesting that mammalian cells are cultivated in excessive glucose. Using RNA‐Seq, this study characterized the Chinese hamster ovary (CHO) cell transcriptome under two glucose concentrations to assess the genetic effects associated with metabolic pathways, in addition to other global responses. The initial extracellular glucose concentrations used represented high (30 mM) and low (10 mM) glucose conditions, where at the time the transcriptomes were compared, the glucose concentrations were approximately 24 and 4.4 mM for the mid‐exponential cultures, where 4.4 mM represents a common target concentration in the biopharmaceutical industry for controlled fed‐batch cultures. A recombinant CHO cell line producing a monoclonal antibody was used, such that the impact on glycosylation genes could be evaluated. Relatively few genes were identified as being significantly different (FDR ≤ 0.01) between the high and low glucose conditions, for example, only 575 genes, and only 40 of these genes had 2‐fold or greater differences. Gene expression differences for glycolysis, TCA cycle, and glycosylation‐related reactions were minimal and unlikely to have biological significance. This transcriptome study indicates that low glucose concentrations in the culture medium are unlikely to cause any biologically significant or detrimental changes to CHO cells at the transcriptome level. Furthermore, it is well‐known that maintaining low glucose concentrations in fed‐batch cultures can reduce lactate production, which in turn improves process outcomes. Taken together, the transcriptome data supports the continued development of low glucose‐based processes to control lactate. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:771–785, 2017
Epitopes rationally selected through computational analyses induce T‐cell proliferation in mice and are recognized by serum from individuals infected with Schistosoma mansoni
Authors: Lopes Marcelo D. , Oliveira Flávio M. , Coelho Ivan E. V. , Passos Maria J. F. , Alves Clarice C. , Taranto Alex G. , Júnior Moacyr C. , Santos Luciana L. , Fonseca Cristina T. , Villar José A. F. P. , Lopes Débora O.
Published: April 2017

Schistosomiasis is the second leading cause of death due to parasitic diseases in the world. Seeking an alternative for the control of disease, the World Health Organization funded the genome sequencing of the major species related to schistosomiasis to identify potential vaccines and therapeutic targets. Therefore, the aim of this work was to select T and B‐cell epitopes from Schistosoma mansoni through computational analyses and evaluate the immunological potential of epitopes in vitro. Extracellular regions of membrane proteins from the Schistosoma mansoni were used to predict promiscuous epitopes with affinity to different human Major Histocompatibility Class II (MHCII) molecules by bioinformatics analysis. The three‐dimensional structure of selected epitopes was constructed and used in molecular docking to verify the interaction with murine MHCII H2‐IAb. In this process, four epitopes were selected and synthesized to assess their ability to stimulate proliferation of CD4+ T lymphocytes in mice splenocyte cultures. The results showed that Sm041370 and Sm168240 epitopes induced significant cell proliferation. Additionally, the four epitopes were used as antigens in the Indirect Enzyme‐Linked Immunosorbent Assay (ELISA) to assess the recognition by serum from individuals infected with Schistosoma mansoni. Sm140560, Sm168240, and Sm041370 epitopes were recognized by infected individuals IgG antibodies. Therefore, Sm041370 and Sm168240 epitopes that stood out in in silico and in vitro analyses could be promising antigens in schistosomiasis vaccine development or diagnostic kits. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:804–814, 2017
Differential scanning calorimetry and fluorimetry measurements of monoclonal antibodies and reference proteins: Effect of scanning rate and dye selection
Authors: Lang Brian E. , Cole Kenneth D.
Published: April 2017

Differential scanning calorimetry (DSC) and differential scanning fluorimetry (DSF) were used to measure the transition temperatures of four proteins: RNase A, invertase, rituximab, and the NISTmAb (NIST Reference Material, RM 8671). The proteins were combined with several different fluorescent dyes for the DSF measurements. This study compares the results of DSC and DSF measurements of transition temperatures with different types of proteins, dye combinations, and thermal scan rates. As protein unfolding is often influenced by kinetic effects, we measured the transition temperatures of the proteins using DSC over a range of temperature scan rates and compared them to the data obtained from DSF over comparable temperature scan rates. The results when the proteins were combined with Sypro Orange® and bis‐ANS for the DSF measurements had the best correlations with the transition temperatures determined by calorimetry. The scan rate was found to be an important variable when comparing results between DSC and DSF. The van't Hoff enthalpy changes for the transitions were calculated from the DSC data by using a non‐two‐state model and from the DSF values using a two‐state model. The calculated van't Hoff enthalpy changes did not show a good correlation between the two methods. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:677–686, 2017
Evaluation of several protein a resins for application to multicolumn chromatography for the rapid purification of fed‐batch bioreactors
Authors: Hilbold Nicolas‐Julian , Le Saoût Xavier , Valery Eric , Muhr Laurence , Souquet Jonathan , Lamproye Alain , Broly Hervé
Published: April 2017

Most of the existing production capacity is based on fed‐batch bioreactors. Thanks to the development of more efficient cell lines and the development of high‐performance culture media, cell productivity dramatically increased. In a manufacturing perspective, it is necessary to clear as quickly as possible the protein A capture step to respect the manufacturing agenda. This article describes the methodology applied for the design of a multicolumn chromatography process with the objective of purifying as quickly as possible 1,000 and 15,000 L fed‐batch bioreactors. Several recent and reference protein A resins are compared based on characteristic values obtained from breakthrough curves. The importance and relevance of resin parameters are explained, and purposely simple indicators are proposed to quickly evaluate the potential of each candidate. Based on simulation data, the optimum BioSC systems associated with each resin are then compared. The quality of the elution delivered by each resin is also compared to complete the assessment. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:941–953, 2017
A nonchromatographic process for purification of secretory immunoglobulins from caprine whey
Authors: Matlschweiger Alexander , Himmler Gottfried , Linhart Clemens , Harasek Michael , Hahn Rainer
Published: April 2017

Secretory immunoglobulins are an important antibody class being primarily responsible for immunoprotection of mucosal surfaces. A simple, non‐chromatographic purification process for secretory immunoglobulins from caprine whey was developed. In the first process step whey was concentrated 30–40‐fold on a 500 kDa membrane, thereby increasing the purity from 3% to 15%. The second step consisted of a fractionated PEG precipitation, in which high molecular weight impurities were removed first and in the second stage the secretory immunoglobulins were precipitated, leaving a majority of the low molecular weight proteins in solution. The re‐dissolved secretory immunoglobulin fraction had a purity of 43% which could then be increased to 72% by diafiltration at a volume exchange factor of 10. Further increase of purity was only possible at the expense of very high buffer consumption. If diafiltration was performed directly after ultrafiltration, followed by precipitation, the yield was higher but purity was only 54%. Overall, filtration performance was characterized by high concentration polarization, therefore process conditions were set to low trans‐membrane pressure and moderate protein concentration. As such purity and to a lesser extent throughput were the major objectives rather than yield, since whey, as a by‐product of the dairy industry, is a cheap raw material of almost unlimited supply. Ultra‐/diafiltration performance was described well by correlations using dimensionless numbers. Compared with a theoretical model (Graetz/Leveque solution) the flux was slightly overestimated. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:642–653, 2017
Protein particulate retention and microorganism recovery for rapid detection of Salmonella
Authors: Ku Seockmo , Kreke Thomas , Ximenes Eduardo , Foster Kirk , Liu Xingya , Gilpin Christopher J. , Ladisch Michael R.
Published: April 2017

The rapid detection of Salmonella in ground meat requires that living microorganisms be brought to levels detectable by PCR, immunoassays, or similar techniques within 8 h. Previously, we employed microfiltration using hollow fiber membranes to rapidly process and concentrate viable bacteria in food extracts through a combination of enzyme treatment and prefiltration in order to prevent blockage or fouling of the hollow fiber membranes. However, scanning electron microscopy and particle size analysis of enzyme hydrolysates showed that enzyme treatment followed by filtration caused submicron particles to form and be trapped within the prefiltration media, which in turn, retained about 80% of the bacteria. Filtering prior to enzyme treatment resulted in formation of a filter cake consisting of protein particles retained on the surface of the filter, while facilitating passage of the much smaller microorganisms through the filter, separating them from particulates. Subsequent enzyme treatment of the filtrate resulted in an extract that was microfiltered in less than an hour, while concentrating viable microorganisms in the extract by 500×. An inoculum of Salmonella enterica cells into turkey burger containing of 1–20 CFU/mL, consisting of spiked cells plus cells already present in the turkey burger sample, was rapidly brought to levels detectable by conventional PCR and BAX® PCR assays. The entire procedure from sample processing to detection of Salmonella enterica was achieved in less than 8 h. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:687–695, 2017
Principles and approach to developing mammalian cell culture media for high cell density perfusion process leveraging established fed‐batch media
Authors: Lin Henry , Leighty Robert Woodrow , Godfrey Scott , Wang Samantha Boran
Published: April 2017

Perfusion medium was successfully developed based on our fed‐batch platform basal and feed media. A systematic development approach was undertaken by first optimizing the ratios of fed‐batch basal and feed media followed by targeted removal of unnecessary and redundant components. With this reduction in components, the medium could then be further concentrated by 2× to increase medium depth. The medium osmolality was also optimized where we found ∼360 mOsm/kg was desirable resulting in a residual culture osmolality of ∼300 mOsm/kg for our cell lines. Further building on this, the amino acids Q, E, N, and D were rebalanced to reduce lactate and ammonium levels, and increase the cell‐specific productivity without compromising on cell viability while leaving viable cell density largely unaffected. Further modifications were also made by increasing certain important vitamin and lipid concentrations, while eliminating other unnecessary vitamins. Overall, an effective perfusion medium was developed with all components remaining in the formulation understood to be important and their concentrations increased to improve medium depth. The critical cell‐specific perfusion rate using this medium was then established for a cell line of interest to be 0.075 nL/cell‐day yielding 1.2 g/L‐day at steady state. This perfusion process was then successfully scaled up to a 100 L single‐use bioreactor with an ATF6 demonstrating similar performance as a 2 L bioreactor with an ATF2. Large volume handling challenges in our fed‐batch facility were overcome by developing a liquid medium version of the powder medium product contained in custom totes for plug‐and‐play use with the bioreactor. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:891–901, 2017
Influence of mixed electrolytes on the adsorption of lysozyme, PEG, and PEGylated lysozyme on a hydrophobic interaction chromatography resin
Authors: Hackemann Eva , Werner Albert , Hasse Hans
Published: April 2017

In a recent work (Werner A and Hasse H in J Chromatogr A 2013;1315:135) the influence of mixed electrolytes on the adsorption of the macromolecules lysozyme, PEG and di‐PEGylated lysozyme on a hydrophobic resin has been studied, but only at one overall ionic strength (3000 mM). The present work, therefore, extends these studies to other ionic strengths (2400 and 2700 mM), and explores the application of a model to predict the entire data set. The adsorbent is Toyopearl PPG‐600M. The solvent is a 25 mM aqueous sodium phosphate buffer at pH 7.0. The studied salts are sodium chloride, sodium sulfate, ammonium chloride and ammonium sulfate. Pure salts as well as binary and ternary mixtures of these salts with varying ratios of the amounts of the salts are studied at 25 °C. The loading of the adsorbent increases with increasing salt concentration for all macromolecules. Synergetic effects of the mixed electrolytes are observed. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1104–1115, 2017
The positive clinical therapeutically effects of Escin on advanced thyroid cancer
Authors: Mei Jin‐Yu , Zhang Ming‐Jun , Wang Yuan‐Yuan , Liu Ye‐Hai
Published: April 2017

The incidences of thyroid cancer keep rising worldwide over the past few decades. Although most thyroid cancers are indolent and highly curable, the treatment for advanced thyroid cancer remains challengeable in clinical practice. We performed two separate cohorts to evaluate the safety and efficiency of Escin in patients with advanced thyroid cancer . In cohort 1, 120 patients were divided into four groups equally and were administrated with placebo or different dosages of Escin. The pharmacokinetics of Escin and the side effects were evaluated. In cohort 2, 120 patients were treated with Escin. Several biomarkers related to the progression of thyroid cancer were evaluated. Kaplan–Meier (KM) analyses were performed to evaluate progression‐free survival (PFS) and overall survival (OS). The serum Escin concentrations were stable during the treatment. Escin (0.6 mg/kg/day for 9 days, intravenous injection) was tolerable for patients with thyroid cancer . Escin significantly reduced the serum levels of TSH, TgAb, Tg, and calcitonin and prolonged the PFS and OS for patients with advanced thyroid cancer. This study showed Escin is efficient and well tolerated in patients with advanced thyroid cancer. Future studies are needed to investigate the mechanism of Escin on thyroid cancer and the proper dosage of Escin clinically.
CCR7 mediates human breast cancer cell invasion, migration by inducing epithelial–mesenchymal transition and suppressing apoptosis through AKT pathway
Authors: Xu Bing , Zhou Minjie , Qiu Wencai , Ye Jueming , Feng Qiming
Published: April 2017

Chemokine and the chemokine receptor have a key role in the tumor progress. Here, we supposed that CCR7 might induce the invasion, migration, and epithelial–mesenchymal transition (EMT) process of breast cancer. In this research, human breast cancer MCF‐7 and MDA‐MB‐231cells were treated with CCL19 and small‐interfering RNA (CCR7 siRNA) for activation and inhibition of CCR7, respectively. Cell invasion and transwell assays were used to detect the effect of CCR7 on invasion and migration. The results demonstrated that CCL19 mediated cell invasion and migration by inducing the EMT, with downregulation of E‐cadherin and up‐regulation of N‐cadherin and vimentin levels. On the other hand, knockdown of CCR7 revealed the changes compared with CCL19 group and the control group. Knockdown of CCR7 inhibits CCL19‐induced breast cancer cell proliferation, the cell cycle, migration, invasion and EMT. Moreover, we demonstrated that CCL19‐induced AKT phosphorylation; however, CCR7 siRNA suppressed CCL19‐induced AKT phosphorylation, a key regulator of tumor metastasis. In conclusion, all findings demonstrated that CCL19/CCR7 axis regulated EMT progress in breast cancer cells and mediated the tumor cell invasion and migration process via activation of AKT signal pathway. Our results suggested that CCR7 may regard as a therapeutic target for the breast cancer treatment.