bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimized protocol for the hepatic differentiation of induced pluripotent stem cells in a fluidic microenvironment
Authors: Danoy Mathieu , Bernier Myriam Lereau , Kimura Keiichi , Poulain Stephane , Kato Sachi , Mori Daiki , Kido Taketomo , Plessy Charles , Kusuhara Hiroyuki , Miyajima Atsushi , Sakai Yasuyuki , Leclerc Eric 
Published: March 2019

AbstractIn the present study, we evaluated the performance of different protocols for the hepatic differentiation of human‐induced pluripotent stem cells (hiPSCs) in microfluidic biochips. Strategies for complete and partial on‐chip differentiation were tested. Unlike full on‐chip differentiation, the transfer of iPSCs from Petri dishes to biochips during the differentiation process produced a heterogeneous tissue with enhanced hepatic features compared with control cultures in Petri dishes. The tissue in biochips was constituted of cells expressing either stabilin‐1 or albumin, while no stabilin‐1 was detected in controls. Functional analysis also revealed double the production rate for albumin in biochips (about 2,000 ng per day per 106 cells). Besides this, tissues obtained in biochips and controls exhibited the metabolism of a specific bile acid. Whole transcriptome analysis with nanoCAGE exhibited a differential expression of 302 genes between control and biochip cultures and a higher degree of hepatic differentiation in biochips, together with increased promoter motif activity for typical liver transcription factors such as estrogen related receptor alpha (
ESRRA), hepatic nuclear factor 1 (
HNF1A), hepatic nuclear factor 4 (
HNF4A), transcription factor 4 (
TCF4), and CCAAT enhancer binding protein alpha (
CEBPA). Gene set enrichment analysis identified several pathways related to the extracellular matrix, tissue reorganization, hypoxia‐inducible transcription factor, and glycolysis that were differentially modulated in biochip cultures. However, the presence of CK19/ALB‐positive cells and the
ɑ‐fetoprotein levels measured in the cultures still reflect primitive differentiation patterns. Overall, we identified key parameters for improved hepatic differentiation on‐chip, including the maturation stage of hepatic progenitors, inoculation density, adhesion time, and perfusion flow rate. Optimization of these parameters further led to establish a protocol for reproducible differentiation of hiPSCs into hepatocyte‐like cells in microfluidic biochips with significant improvements over Petri dish cultures.
Coping with inadvertent lysis of Escherichia coli cultures: Strains resistant to lysogeny and infection by the stealthy lysogenic phage Φ80
Authors: Srinivas Swaminath , Cronan John E 
Published: March 2019

AbstractPhage Φ80 can infect Escherichia coli in a stealthy manner and persist by forming lysogens. Such Φ80 lysogens are fairly common and often go undetected unless the host is grown at temperatures below 37°C. Since low growth temperatures are required for growing temperature‐sensitive mutants and often preferred for large‐scale applications such as protein production, Φ80‐resistant strains would be useful. We report the construction of E. coli strains that cannot be efficiently lysogenized or infected by bacteriophage Φ80. These strains contain combinations of deletions or mutations in the bacterial attachment site for Φ80 integration and/or deletions in the genes required for phage absorption to the host outer membrane. These strains should help contain and prevent Φ80 infection of E. coli cultures in a laboratory or industrial setting.
Adenovirus 5 recovery using nanofiber ion‐exchange adsorbents
Authors: Turnbull Jordan , Wright Bernice , Green Nicola K. , Tarrant Richard , Roberts Iwan , Hardick Oliver , Bracewell Daniel G. 
Published: March 2019

AbstractViral vectors such as adenovirus have successful applications in vaccines and gene therapy but the manufacture of the high‐quality virus remains a challenge. It is desirable to use the adsorption‐based chromatographic separations that so effectively underpin the therapeutic protein manufacture. However fundamental differences in the size and stability of this class of product mean it is necessary to revisit the design of sorbent's morphology and surface chemistry. In this study, the behaviour of a cellulose nanofiber ion‐exchange sorbent derivatised with quaternary amine ligands at defined densities is characterised to address this. This material was selected as it has a large accessible surface area for viral particles and rapid process times. Initially, the impact of surface chemistry on infective product recovery using low (440 µmol/g), medium (750 µmol/g), and high (1029 µmol/g) ligand densities is studied. At higher densities product stability is reduced, this effect increased with prolonged adsorption durations of 24 min with just ~10% loss at low ligand density versus ~50% at high. This could be mitigated by using a high flow rate to reduce the cycle time to ~1 min. Next, the impact of ligand density on the separation's resolution was evaluated. Key to understanding virus quality is the virus particle: infectious virus particle ratio. It was found this parameter could be manipulated using ligand density and elution strategy. Together this provides a basis for viral vector separations that allows for their typically low titres and labile nature by using high liquid velocity to minimise both load and on‐column times while separating key product and process‐related impurities.
Impact of resection margin status on recurrence and survival in pancreatic cancer surgery
Authors: Tummers W S , Groen J V , Sibinga Mulder B G , Farina-Sarasqueta A , Morreau J , Putter H , van de Velde C J , Vahrmeijer A L , Bonsing B A , Mieog J S , Swijnenburg R J 
Published: March 2019

AbstractBackgroundThe prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is poor and selection of patients for surgery is challenging. This study examined the impact of a positive resection margin (R1) on locoregional recurrence (LRR) and overall survival (OS); and also aimed to identified tumour characteristics and/or technical factors associated with a positive resection margin in patients with PDAC.MethodsPatients scheduled for pancreatic resection for PDAC between 2006 and 2016 were identified from an institutional database. The effect of resection margin status, patient characteristics and tumour characteristics on LRR, distant metastasis and OS was assessed.ResultsA total of 322 patients underwent pancreatectomy for PDAC. A positive resection (R1) margin was found in 129 patients (40·1 per cent); this was associated with decreased OS compared with that in patients with an R0 margin (median 15 (95 per cent c.i. 13 to 17) versus 22 months; P &lt; 0·001). R1 status was associated with reduced time to LRR (median 16 versus 36 (not estimated, n.e.) months; P = 0·002). Disease recurrence patterns were similar in the R1 and R0 groups. Risk factors for early recurrence were tumour stage, positive lymph nodes (N1) and perineural invasion. Among 100 patients with N0 disease, R1 status was associated with shorter OS compared with R0 resection (median 17 (10 to 24) versus 45 (n.e.) months; P = 0·002), whereas R status was not related to OS in 222 patients with N1 disease (median 14 (12 to 16) versus 17 (15 to 19) months after R1 and R0 resection respectively; P = 0·068).ConclusionAlthough pancreatic resection with a positive margin was associated with poor survival and early recurrence, particularly in patients with N1 disease, disease recurrence patterns were similar between R1 and R0 groups.
Self‐reported navigation ability is associated with optic flow‐sensitive regions’ functional connectivity patterns during visual path integration
Authors: Zajac Lauren , Burte Heather , Taylor Holly A. , Killiany Ronald 
Published: March 2019

AbstractIntroductionSpatial navigation is a complex cognitive skill that varies between individuals, and the mechanisms underlying this variability are not clear. Studying simpler components of spatial navigation may help illuminate factors that contribute to variation in this complex skill; path integration is one such component. Optic flow provides self‐motion information while moving through an environment and is sufficient for path integration. This study aims to investigate whether self‐reported navigation ability is related to information transfer between optic flow‐sensitive (OF‐sensitive) cortical regions and regions important to navigation during environmental spatial tasks.MethodsFunctional magnetic resonance imaging was used to define OF‐sensitive regions and map their functional connectivity (FC) with the retrosplenial cortex and hippocampus during visual path integration (VPI) and turn counting (TC) tasks. Both tasks presented visual self‐motion through a real‐world environment. Correlations predicting a positive association between self‐reported navigation ability (measured with the Santa Barbara Sense of Direction scale) and FC strength between OF‐sensitive regions and retrosplenial cortex and OF‐sensitive regions and the hippocampus were performed.ResultsDuring VPI, FC strength between left cingulate sulcus visual area (L CSv) and right retrosplenial cortex and L CSv and right hippocampus was positively associated with self‐reported navigation ability. FC strength between right cingulate sulcus visual area (R CSv) and right retrosplenial cortex during VPI was also positively associated with self‐reported navigation ability. These relationships were specific to VPI, and whole‐brain exploratory analyses corroborated these results.ConclusionsThese findings support the hypothesis that perceived spatial navigation ability is associated with communication strength between OF‐sensitive and navigationally relevant regions during visual path integration, which may represent the transformation accuracy of visual motion information into internal spatial representations. More broadly, these results illuminate underlying mechanisms that may explain some variability in spatial navigation ability.
Cross‐linked enzyme aggregates of recombinant Candida antarctica lipase B for the efficient synthesis of olvanil, a nonpungent capsaicin analogue
Authors: Diaz‐Vidal Tania , Armenta‐Perez Vicente Paul , Rosales‐Rivera Luis Carlos , Mateos‐Díaz Juan C. , Rodríguez Jorge A. 
Published: March 2019

AbstractDespite the proven therapeutic role of capsaicin in human health, its usage is still hampered by its high pungency. In this sense, nonpungent capsaicin analogues as olvanil are a feasible alternative to the unpleasant sensations produced by capsaicin while maintaining a similar pharmacological profile. Olvanil can be obtained by a lipase‐catalyzed chemoenzymatic process. In the present work, recombinant Candida antarctica lipase B (CALB) was expressed in Pichia pastoris and subsequently immobilized by cross‐linked enzyme aggregate (CLEA) methodology for the synthesis of olvanil. The CALB‐CLEAs were obtained directly from the fermentation broth of P. pastoris without any purification step in order to assess the role of the contaminant proteins of the crude extract as co‐feeders. The CALB‐CLEAs were also bioimprinted to enhance the catalytic performance in olvanil synthesis. When CALB was precipitated with isopropanol, the obtained CALB‐CLEAs exhibited the highest activity in the synthesis of olvanil, regardless of the glutaraldehyde concentration. The maximum product synthesis was found at 72 hr obtaining 6.8 g L−1 of olvanil with a reaction yield of 16%. When CALB was bioimprinted with olvanil, the synthesis was enhanced 1.3 times, reaching 10.7 g L−1 of olvanil at 72 hr of reaction with a reaction yield of 25%. Scanning electron microscopy images indicated different morphologies of the CLEAs depending on the precipitating agent and the template used for bioimprinting. Recombinant CALB‐CLEAs obtained directly from the fermentation broth are a suitable alternative to commercial enzymatic preparations for the synthesis of olvanil in organic medium.
Chemical and Electrochemical Lithiation of van der Waals Tetrel‐Arsenides
Authors: Mark Justin , Hanrahan Michael P. , Woo Katherine E. , Lee Shannon , Rossini Aaron J. , Kovnir Kirill 
Published: March 2019

AbstractLithiation of van der Waals tetrel‐arsenides, GeAs and SiAs, has been investigated. Electrochemical lithiation demonstrated large initial capacities of over 950 mAh g−1 accompanied by rapid fading over successive cycling in the voltage range 0.01–2 V. Limiting the voltage range to 0.5–2 V achieved more stable cycling, which was attributed to the intercalation process with lower capacities. Ex situ powder X‐ray diffraction confirmed complete amorphization of the samples after lithiation, as well as recrystallization of the binary tetrel‐arsenide phases after full delithiation in the voltage range 0.5–2 V. Solid‐state synthetic methods produce layered phases, in which Si‐As or Ge‐As layers are separated by Li cations. The first layered compounds in the corresponding ternary systems were discovered, Li0.9Ge2.9As3.1 and Li3Si7As8, which crystallize in the Pbam (No. 55) and P2/m (No. 10) space groups, respectively. Semiconducting layered GeAs and SiAs accommodate the extra charge from Li cations through structural rearrangement in the Si‐As or Ge‐As layers and eventually by replacement of the tetrel dumbbells with sets of Li atoms. Ge and Si monoarsenides demonstrated high structural flexibility and a mild ability for reversible lithiation.
Manganese(III) Porphyrin‐Catalyzed Dehydrogenation of Alcohols to form Imines, Tertiary Amines and Quinolines
Authors: Azizi Kobra , Akrami Sedigheh , Madsen Robert 
Published: March 2019

AbstractManganese(III) porphyrin chloride complexes have been developed for the first time as catalysts for the acceptorless dehydrogenative coupling of alcohols and amines. The reaction has been applied to the direct synthesis of imines, tertiary amines and quinolines where only hydrogen gas and/or water are formed as the by‐product(s). The mechanism is believed to involve the formation of a manganese(III) alkoxide complex which degrades into the aldehyde and a manganese(III) hydride species. The latter reacts with the alcohol to form hydrogen gas and thereby regenerates the alkoxide complex.
Rapid Access to Oxa‐Bridged Bicyclic Skeletons through Gold‐Catalyzed Tandem Rearrangement Reaction
Authors: Zhang Jiantao , Liao Zhehui , Chen Lianfen , Zhu Shifa 
Published: March 2019

AbstractA gold (I)‐catalyzed reaction of enyne‐ethers to rapidly construct oxa‐bridged compounds via a tandem 1,2‐acyloxy migration/intramolecular oxonium formation/1,2‐rearrangement process was reported. The reaction was shown to be robust with a wide range of substitution patterns tolerated to provide the corresponding oxygen‐containing bridged products in good to excellent yields.
Colourful questions of an Indian village
Authors: Smith Dianne 
Published: March 2019

AbstractHow we understand and recall colour in the environments we encounter is reliant on the context. Drawing on a repeated experience of the author in a rural Indian village, a number of questions were raised regarding visual distinctiveness and its impact on the identity of place embedded in the memories of the village. A photographic walk‐through was undertaken to determine the existing colour palette and its relationship to the character of the memories of the village. Combined with observations and theory drawn from the literature, it is proposed that considering the experience from a pluralist perspective enables insights to emerge. In this case, colour moments and colour contrast are key attributes of memories and identity construction for the village visitor.
Dennd1a, a susceptibility gene for polycystic ovary syndrome, is essential for mouse embryogenesis
Authors: Shi Jingjing , Gao Qing , Cao Yongzhi , Fu Jiang 
Published: March 2019

AbstractBackgroundThe DENND1A has been identified as a guanine nucleotide exchange factor for small GTPase Rab35, which functions in endocytic trafficking to mediate the recycling of selective cargos. Genetic alterations within the DENND1A gene have been implicated in human disease such as polycystic ovary syndrome (PCOS). However, the role of DENND1A in developmental and reproductive processes is largely unknown.ResultsUsing Dennd1a gene knockout mice, we uncovered that homogeneous Dennd1a−/− mutants died around embryonic day (E) 14.5. The brain of Dennd1a−/− embryos exhibited defects, partially attributed to the dysregulation of cell division and survival in the telencephalon. The transcription of Fgf8 mRNA was ectopically elevated in the dorsal midline of telencephalon, concomitant with a decrease of active β‐catenin and Axin2 in the brain of Dennd1a−/− embryos. During liver morphogenesis, the ablation of Dennd1a impaired hepatic cell proliferation, the differentiation of hepatocyte, and hepatic hematopoiesis. In addition, loss of Dennd1a also affected the development of primordial germ cells.ConclusionsWe demonstrate that Dennd1a, a susceptibility gene for PCOS, is essential for embryogenesis, probably through the mediation of endocytic recycling of selective cargos that are involved in cell signaling crucial for the development of multiple embryonic organ systems.
Mice conditionally expressing RET(C618F) mutation display C cell hyperplasia and hyperganglionosis of the enteric nervous system
Authors: Okamoto Mitsumasa , Yoshioka Yuta , Maeda Kosaku , Bito Yuko , Fukumoto Takumi , Uesaka Toshihiro , Enomoto Hideki 
Published: March 2019

SummaryMedullary thyroid carcinoma (MTC) develops from hyperplasia of thyroid C cells and represents one of the major causes of thyroid cancer mortality. Mutations in the cysteine‐rich domain (CRD) of the RET gene are the most prevalent genetic cause of MTC. The current consensus holds that such cysteine mutations cause ligand‐independent dimerization and constitutive activation of RET. However, given the number of the CRD mutations left uncharacterized, our understanding of the pathogenetic mechanisms by which CRD mutations lead to MTC remains incomplete. We report here that RET(C618F), a mutation identified in MTC patients, displays moderately high basal activity and requires the ligand for its full activation. To assess the biological significance of RET(C618F) in organogenesis, we generated a knock‐in mouse line conditionally expressing RET(C618F) cDNA by the Ret promoter. The RET(C618F) allele can be made to be Ret‐null and express mCherry by Cre‐loxP recombination, which allows the assessment of the biological influence of RET(C618F) in vivo. Mice expressing RET(C618F) display mild C cell hyperplasia and increased numbers of enteric neurons, indicating that RET(C618F) confers gain‐of‐function phenotypes. This mouse line serves as a novel biological platform for investigating pathogenetic mechanisms involved in MTC and enteric hyperganglionosis.
The relationship between body mass index, body dissatisfaction, and eating pathology in sexual minority women
Authors: Jones Cherrelle L. , Fowle Jillianne L. , Ilyumzhinova Rimma , Berona Johnny , Mbayiwa Kimberley , Goldschmidt Andrea B. , Bodell Lindsay P. , Stepp Stephanie D. , Hipwell Alison E. , Keenan Kate E. 
Published: March 2019

AbstractObjectiveEating pathology is more prevalent among women compared to men, but prevalence and correlates associated with eating pathology likely vary among subgroups of women. This study examines prevalence and correlates of restrictive and weight control‐related eating pathology in sexual minority women.MethodData were collected from the Pittsburgh Girls Study (PGS). Participants reported on sexual orientation, and race, and body mass index (BMI) was derived from interviewer collected height and weight. Participants completed the Body Image Measure and the Eating Attitudes Test‐26.ResultsSexual minority women reported higher BMIs [F (1, 862) = 14.69, p < .001], higher levels of body dissatisfaction [F (1, 960) = 3.12, p < .01], and higher levels of eating pathology [F (1, 950) = 14.21, p < .001] than heterosexual women. Body dissatisfaction mediated the relationship between BMI and eating pathology, and levels of associations were not attenuated by sexual minority status. Race moderated the association between sexual orientation and eating pathology; compared to all other groups, White sexual minority women had the highest level of eating pathology.DiscussionResults indicate that White sexual minority women have higher levels of eating pathology than Black sexual minority women and both Black and White heterosexual women. Future studies that draw from larger and more diverse, community‐based samples are needed.
Thermal design and optimization of lithium ion batteries for unmanned aerial vehicles
Authors: Ma Yanjun , Chiang Sum Wai , Chu Xiaodong , Li Jia , Gan Lin , Xu Chengjun , Yao Youwei , He Yanbing , Li Baohua , Kang Feiyu , Du Hongda 
Published: March 2019

AbstractIn this article, a novel lithium ion batteries thermal design to manage ultrahigh thermal shock of a commercial small four‐rotor electric unmanned aerial vehicle (UAV) is developed and optimized. The cooling relies on internal heat pipe and convective cooling of UAV body, so that the heat generated by the battery can reach exterior cooling through a dedicated thermal path. The thermal management system is passive and requires no additional energy consumption. Finite element simulation is established to model the system and advanced thermal materials, and the system is optimized by response surface method in a dual objectives approach: minimizing maximum battery temperature and weight of the UAV. Simulation results show that the new passive cooling system can keep the temperature of the lithium ion battery within a reasonable range. The effects of convective heat transfer coefficient, discharge rate, and fuselage thermal conductivity were studied. After optimizing the system, the highest temperature of battery discharging at 3C rate can be kept no more than 36°C in the cost of 32.18 g weight increment.
Resource allocation in RF energy harvesting‐assisted underlay D2D communication
Authors: Yu Shuo , Ejaz Waleed , Guan Ling , Anpalagan Alagan , Rizvi Imran A. 
Published: March 2019

AbstractDevice to device (D2D) communication is capable to address the increasing demand for data rates in fifth generation (5G) and beyond networks. However, D2D communication is usually convoluted with interference scenarios since both D2D users and cellular users share the same spectrum resources. Furthermore, D2D systems can trace back to limited battery life. The battery life problem is becoming more challenging with the exponential increase of devices in the future networks. Therefore, efficient resource allocation schemes need investigation to offer better quality of service for both cellular and D2D users under the constraints of interference and energy. In this paper, we address these two problems (interference and energy) simultaneously by efficiently allocating resources in energy harvesting‐assisted underlay D2D communication. We propose a deterministic model in which D2D users harvest energy only when required. We propose a resource allocation scheme, which jointly allocate resources and transmit power. We formulate an optimization problem with an objective to maximize sum throughput of D2D system while satisfying constraints on quality of service, power, and interference. To solve the problem, we adopt the nonlinear optimization by mesh adaptive direct search algorithm to obtain the suboptimal solution. We show the effectiveness of the proposed scheme in comparison with existing algorithms through simulation results.