bluuebunny/crossref_metadata_2025 huggingface dataset:
Single Carbon Fibers with a Macroscopic‐Thickness, 3D Highly Porous Carbon Nanotube Coating
Authors: Zou Mingchu , Zhao Wenqi , Wu Huaisheng , Zhang Hui , Xu Wenjing , Yang Liusi , Wu Shiting , Wang Yunsong , Chen Yijun , Xu Lu , Cao Anyuan
Published: February 2018

Carbon fiber (CF) grafted with a layer of carbon nanotubes (CNTs) plays an important role in composite materials and other fields; to date, the applications of CNTs@CF multiscale fibers are severely hindered by the limited amount of CNTs grafted on individual CFs and the weak interfacial binding force. Here, monolithic CNTs@CF fibers consisting of a 3D highly porous CNT sponge layer with macroscopic‐thickness (up to several millimeters), which is directly grown on a single CF, are fabricated. Mechanical tests reveal high sponge–CF interfacial strength owing to the presence of a thin transitional layer, which completely inhibits the CF slippage from the matrix upon fracture in CNTs@CF fiber–epoxy composites. The porous conductive CNTs@CF hybrid fibers also act as a template for introducing active materials (pseudopolymers and oxides), and a solid‐state fiber‐shaped supercapacitor and a fiber‐type lithium‐ion battery with high performances are demonstrated. These CNTs@CF fibers with macroscopic CNT layer thickness have many potential applications in areas such as hierarchically reinforced composites and flexible energy‐storage textiles.
In situ Optical Study of Gold Nanorod Coupling with Graphene
Authors: Zhao Jingyi , Cao Zhengmin , Cheng Yuqing , Xu Jianning , Wen Te , Hu Aiqin , Gong Qihuang , Lu Guowei
Published: February 2018

Electron or energy transfer process is critical to understand the interaction between graphene and metal nanostructures. Combining atomic force microscope nanomanipulation with single‐particle spectroscopy enables in situ investigation of the interaction between single gold nanorod and monolayer graphene. This paper reveals that scattering and photoluminescence intensity of the nanorod decreased after coupling with monolayer graphene. The coupling strength is distance dependent and different for diverse nanoparticles, resulting in intensity quenching ratio varying from 20% to 60%, and broadening of resonance linewidth varying from 18 to 38 meV. These results clarify previous controversy between ensemble studies and single‐particle measurements, and that contributes to the deeper understanding of plasmonic graphene hybrids.
Photomultiplication Type Organic Photodetectors with Broadband and Narrowband Response Ability
Authors: Miao Jianli , Zhang Fujun , Du Mingde , Wang Wenbin , Fang Ying
Published: February 2018

It is a great challenge to achieve highly sensitive organic photodetectors (OPDs) with broadband and narrowband response ability. The OPDs with an extraordinary structure of ITO/PFN‐OX/P3HT:PTB7‐Th:PC61BM (100‐x:x:1, wt/wt/wt)/Al are elaborately fabricated, exhibiting tunable spectral response dependent on the bias polarity. The optimized ternary OPDs with 3 µm P3HT:PTB7‐Th:PC61BM (40:60:1) as active layers exhibit broadband spectral response from 350 to 800 nm under forward bias and narrowband spectral response from 750 to 850 nm with a full width half maximum (FWHM) of ≈40 nm under reverse bias. In particular, the FWHM of narrowband response windows can be kept well under different reverse biases. Moreover, the optimized ternary OPDs also exhibit photomultiplication (PM) phenomenon under forward and reverse bias, resulting from the interfacial trap‐assisted hole tunneling injection from external circuit. This should be the first demonstration of PM type OPDs with broadband and narrowband response ability, which would possess wide potential applications, especially in integrated optoelectronic products.
Intermolecular Electrochemical C(sp3)‐H/N‐H Cross‐coupling of Xanthenes with N‐alkoxyamides: Radical Pathway Mediated by Ferrocene as a Redox Catalyst
Authors: Lin Meng‐Ying , Xu Kun , Jiang Yang‐Ye , Liu Yong‐Guo , Sun Bao‐Guo , Zeng Cheng‐Chu
Published: February 2018

Efficient intermolecular dehydrogenative cross‐coupling of N‐alkyloxyamides with xanthenes is reported. The protocol is carried out in an undivided cell under constant current conditions employing simple, cheap and readily available ferrocene (Fc) as a redox catalyst. Cyclic voltammetry and control experiments disclosed that the dehydrogenative cross‐coupling reaction may proceed via an amidyl radical.

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Synthesis and properties of an acrylamide‐based polymer for enhanced oil recovery: A preliminary study
Authors: Wu Gang , Yu Liangmin , Jiang Xiaohui
Published: February 2018

This research evaluates performance of an acrylamide‐based polymer which can be used for displacing reservoir oil. Three associated polymeric systems were proposed based on hydrolyzed polyacrylamide (HPAM), reported PAAHO, and the novel synthesized and characterized functionalized copolymer PAAHAI. Polymer solution behaviors were used to examine the changes in viscosity when the polymer was applied under certain reservoir conditions. PAAHAI showed a higher resistance and tolerance to temperature and salt content than HPAM and PAAHO. The antimicrobial degradation rates of PAAHAI could reach up to 13.2% and 21.7% for Bacillus sp. PAH‐2 and Pseudomonas sp. LP‐7, respectively. The inhibition efficiency of PAAHAI could reach as high as 93.08% in 1M HCl at 25°C. These results indicate that PAAHAI can be suitable for application in enhanced oil recovery.
Thickness‐dependent optical and structural properties of polytetrafluoroethylene/zinc oxide films by radio frequency magnetron sputtering
Authors: Tripathi Shilpa , De Rajnarayan , Rao Kompalli D. , Haque Sheikh M. , Goud Bhujagouni K. , Prathap Chillakala , Misal Jitendra S. , Patidar Manju M. , Ganesan Vedachalaiyer , Sahoo Naba K.
Published: February 2018

PTFE/ZnO films with varying ZnO thickness were prepared by RF magnetron sputtering under high vacuum (100W RF power). The PTFE/ZnO films show slight enhancement in transmission in the visible range as compared to bare ZnO films. There is a clear UV light cutoff (rapid fall below 380 nm with negligible transmission below ~300 nm) after 10‐min deposition of ZnO, which remains unaffected by further depositing PTFE. Transmission data reveal that absorption edge falls in the range of 300–380 nm, below which, the transmission reduced to only ~0.02% giving an optical density of 4 (for the film deposited for 20 min [total thickness ~415 nm]) in the 200–250 nm range. As the ZnO layer thickness increases, the polycrystallinity increases and simultaneously, roughness increases. It leads to a change in crystallite orientations and also in the distribution of grains on film surface. Corresponding AFM image shows island‐like growth, leading to an intermixed ZnO/PTFE layer. The roughness of surface in lower as well as higher thickness range is found to be high (~8–9 nm) except the film in which continuous layer seems to be grown. Based on this, a layer model was developed that consists of glass substrate, native oxide SiO2 layer on this substrate, then a dense ZnO layer followed by mixed PTFE/ZnO layer which is then covered by top PTFE as evident from the ellipsometry fitting. Overall results suggest that by choosing proper thicknesses and number of layers, such thin films might be used in antireflection coatings with UV protection below 400 nm. Based on these experimental results, an optimized simulated layer model consisting of suitable layer thicknesses of ZnO and PTFE has been suggested to achieve high transmission in the visible wavelength region.
Interface Modulation and Optimization of Electrical Properties of HfGdO/GaAs Gate Stacks by ALD‐Derived Al2O3 Passivation Layer and Forming Gas Annealing
Authors: Jiang Shanshan , He Gang , Liu Mao , Zhu Li , Liang Shuang , Li Wendong , Sun Zhaoqi , Tian Mingliang
Published: February 2018

Metal‐oxide‐semiconductor (MOS) capacitors with sputtering‐deposited Gd‐doped HfO2(HGO) high k gate dielectric thin films and ALD‐derived Al2O3 interfacial passivation layer were fabricated on GaAs substrates. The effects of the passivation layer and the forming gas annealing (FGA) temperature were explored by studying the interfacial chemical bonding states and electrical properties of HGO/GaAs and HGO/Al2O3/GaAs gate stacks via x‐ray photoelectron spectroscopy (XPS), capacitance‐voltage (C–V), and leakage current density‐voltage ( J–V) measurements. Results indicated that the MOS capacitors performances were enhanced by performing FGA. The electrical analysis revealed that the 300 °C‐annealed Al/HGO/GaAs/Al MOS capacitor with 20 cycles Al2O3 passivation layer experienced improved electrical properties, with a dielectric constant of 44, a flat band voltage of 0.64 V, a hysteresis of 0.02 V corresponding to the oxide charge density of −6.2 × 1012 cm2, border trapped oxide charge density of −3.02 × 1011 cm2, a leakage current density 5.87 × 10‐6 A/cm2 at a bias voltage of 2 V. The low temperature (77–300 K) dependent detailed current conduction mechanisms (CCMs) of the 300 °C‐annealed MOS capacitor at low temperatures were also systematically investigated. The optimized interface chemistry and the excellent electrical properties suggested that HGO/Al2O3/GaAs potential gate stacks could be applied in future III‐V‐based MOSFET devices.
Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein–Taybi syndrome
Authors: Menke Leonie A. ,   The DDD study, Gardeitchik Thatjana , Hammond Peter , Heimdal Ketil R. , Houge Gunnar , Hufnagel Sophia B. , Ji Jianling , Johansson Stefan , Kant Sarina G. , Kinning Esther , Leon Eyby L. , Newbury‐Ecob Ruth , Paolacci Stefano , Pfundt Rolph , Ragge Nicola K. , Rinne Tuula , Ruivenkamp Claudia , Saitta Sulagna C. , Sun Yu , Tartaglia Marco , Terhal Paulien A. , van Essen Anthony J. , Vigeland Magnus D. , Xiao Bing , Hennekam Raoul C.
Published: February 2018

In 2016, we described that missense variants in parts of exons 30 and 31 of CREBBP can cause a phenotype that differs from Rubinstein–Taybi syndrome (RSTS). Here we report on another 11 patients with variants in this region of CREBBP (between bp 5,128 and 5,614) and two with variants in the homologous region of EP300. None of the patients show characteristics typical for RSTS. The variants were detected by exome sequencing using a panel for intellectual disability in all but one individual, in whom Sanger sequencing was performed upon clinical recognition of the entity. The main characteristics of the patients are developmental delay (90%), autistic behavior (65%), short stature (42%), and microcephaly (43%). Medical problems include feeding problems (75%), vision (50%), and hearing (54%) impairments, recurrent upper airway infections (42%), and epilepsy (21%). Major malformations are less common except for cryptorchidism (46% of males), and cerebral anomalies (70%). Individuals with variants between bp 5,595 and 5,614 of CREBBP show a specific phenotype (ptosis, telecanthi, short and upslanted palpebral fissures, depressed nasal ridge, short nose, anteverted nares, short columella, and long philtrum). 3D face shape demonstrated resemblance to individuals with a duplication of 16p13.3 (the region that includes CREBBP), possibly indicating a gain of function. The other affected individuals show a less specific phenotype. We conclude that there is now more firm evidence that variants in these specific regions of CREBBP and EP300 result in a phenotype that differs from RSTS, and that this phenotype may be heterogeneous.
The molecular epidemiology of Huntington disease is related to intermediate allele frequency and haplotype in the general population
Authors: Kay Chris , Collins Jennifer A. , Wright Galen E.B. , Baine Fiona , Miedzybrodzka Zosia , Aminkeng Folefac , Semaka Alicia J. , McDonald Cassandra , Davidson Mark , Madore Steven J. , Gordon Erynn S. , Gerry Norman P. , Cornejo‐Olivas Mario , Squitieri Ferdinando , Tishkoff Sarah , Greenberg Jacquie L. , Krause Amanda , Hayden Michael R.
Published: February 2018

Huntington disease (HD) is the most common monogenic neurodegenerative disorder in populations of European ancestry, but occurs at lower prevalence in populations of East Asian or black African descent. New mutations for HD result from CAG repeat expansions of intermediate alleles (IAs), usually of paternal origin. The differing prevalence of HD may be related to the rate of new mutations in a population, but no comparative estimates of IA frequency or the HD new mutation rate are available. In this study, we characterize IA frequency and the CAG repeat distribution in fifteen populations of diverse ethnic origin. We estimate the HD new mutation rate in a series of populations using molecular IA expansion rates. The frequency of IAs was highest in Hispanic Americans and Northern Europeans, and lowest in black Africans and East Asians. The prevalence of HD correlated with the frequency of IAs by population and with the proportion of IAs found on the HD‐associated A1 haplotype. The HD new mutation rate was estimated to be highest in populations with the highest frequency of IAs. In European ancestry populations, one in 5,372 individuals from the general population and 7.1% of individuals with an expanded CAG repeat in the HD range are estimated to have a molecular new mutation. Our data suggest that the new mutation rate for HD varies substantially between populations, and that IA frequency and haplotype are closely linked to observed epidemiological differences in the prevalence of HD across major ancestry groups in different countries.
Computed tomography analysis of frontal cell prevalence according to the International Frontal Sinus Anatomy Classification
Authors: Choby Garret , Thamboo Andrew , Won Tae‐Bin , Kim Jooyeon , Shih Liang Chun , Hwang Peter H.
Published: February 2018

Background

The International Frontal Sinus Anatomy Classification (IFAC) is an international consensus document published in 2016 to standardize the nomenclature of cells in the region of the frontal recess and frontal sinus. The IFAC was designed to be surgically relevant and anatomically precise. The current study was undertaken to assess the prevalence of the frontal cell variants as defined by the IFAC, as well as to determine the interrater reliability of the IFAC.

Methods

Three independent reviewers examined triplanar nondiseased maxillofacial computed tomography (CT) scans to assess the anatomy of the frontal recess according to the IFAC system. The prevalence of each cell type was assessed and interrater reliability was measured using an intraclass correlation coefficient (ICC).

Results

One hundred CT scans (200 sides) were examined. Of the 200 sides, 96.5% contained an agger nasi cell (ICC, 0.82; 95% confidence interval [CI], 0.77‐0.86), 30.0% contained a supra agger cell (ICC, 0.89; 95% CI, 0.86‐0.92), 20.0% contained a supra agger frontal cell (ICC 0.80; 95% CI 0.74‐0.84), 72.0% contained a supra bulla cell (ICC, 0.81; 95% CI, 0.76‐0.85), 5.5% contained a supra bulla frontal cell (ICC, 0.71; 95% CI, 0.63‐0.77), 28.5% contained a supraorbital ethmoid cell (ICC, 0.78; 95% CI, 0.72‐0.83), and 30.0% contained a frontal septal cell (ICC, 0.80; 95% CI, 0.74‐0.84). The ICC was good to excellent for identification of all frontal cell types.

Conclusions

This study describes the normative distribution of frontal recess cells in a nondiseased population according to IFAC and demonstrates favorable interrater reliability of the classification system.
Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia
Authors: Avansini Simoni H. , Torres Fábio R. , Vieira André S. , Dogini Danyella B. , Rogerio Fabio , Coan Ana C. , Morita Marcia E. , Guerreiro Marilisa M. , Yasuda Clarissa L. , Secolin Rodrigo , Carvalho Benilton S. , Borges Murilo G. , Almeida Vanessa S. , Araújo Patrícia A. O. R. , Queiroz Luciano , Cendes Fernando , Lopes‐Cendes Iscia
Published: February 2018

Objective

Focal cortical dysplasias (FCDs) are an important cause of drug‐resistant epilepsy. In this work, we aimed to investigate whether abnormal gene regulation, mediated by microRNA, could be involved in FCD type II.

Methods

We used total RNA from the brain tissue of 16 patients with FCD type II and 28 controls. MicroRNA expression was initially assessed by microarray. Quantitative polymerase chain reaction, in situ hybridization, luciferase reporter assays, and deep sequencing for genes in the mTOR pathway were performed to validate and further explore our initial study.

Results

hsa‐let‐7f (p = 0.039), hsa‐miR‐31 (p = 0.0078), and hsa‐miR34a (p = 0.021) were downregulated in FCD type II, whereas a transcription factor involved in neuronal and glial fate specification, NEUROG2 (p < 0.05), was upregulated. We also found that the RND2 gene, a NEUROG2‐target, is upregulated (p < 0.001). In vitro experiments showed that hsa‐miR‐34a downregulates NEUROG2 by binding to its 5′‐untranslated region. Moreover, we observed strong nuclear expression of NEUROG2 in balloon cells and dysmorphic neurons and found that 28.5% of our patients presented brain somatic mutations in genes of the mTOR pathway.

Interpretation

Our findings suggest a new molecular mechanism, in which NEUROG2 has a pivotal and central role in the pathogenesis of FCD type II. In this way, we found that the downregulation of hsa‐miR‐34a leads to upregulation of NEUROG2, and consequently to overexpression of the RND2 gene. These findings indicate that a faulty coupling in neuronal differentiation and migration mechanisms may explain the presence of aberrant cells and complete dyslamination in FCD type II. Ann Neurol 2018;83:623–635
Rissbreiten an biegebeanspruchten Bauteilen
Authors: Empelmann Martin , Cramer Jonas
Published: February 2018

Obwohl die Rechenansätze zur Ermittlung der Rissbreiten überwiegend an Zugstäben abgeleitet wurden, werden diese in der Praxis auch für die Berechnung von Rissbreiten an biegebeanspruchten Bauteilen angewendet, zum Teil auch, weil entsprechende Angaben in den Bemessungsnormen fehlen. Die bei Biegung vorhandenen rissaufweitenden Faktoren können aber im Vergleich zum „Zugstab‐Rechenwert“ zu einer deutlichen Erhöhung der Rissbreiten am Bauteil führen. Im vorliegenden Beitrag werden die wesentlichen Unterschiede der Rissbildung unter Zug‐ und Biegebeanspruchung erläutert, Einflussfaktoren identifiziert und Vergleiche mit Versuchsergebnissen durchgeführt. Ziel ist es, einen Überblick über die einzelnen Faktoren zu vermitteln, sodass abhängig von projektspezifischen Anforderungen und für eine bessere Vorhersage die am Zugstab abgeleiteten Rissbreitenformeln auf biegebeanspruchte Bauteile erweitert werden können.
Participation in bowel screening among men attending abdominal aortic aneurysm screening
Authors: Quyn A J , Fraser C G , Rodger J , Digan A , Anderson A S , Steele R J C
Published: February 2018

Background

Uptake of population-based screening for colorectal cancer in Scotland is around 55 per cent. Abdominal aortic aneurysm (AAA) screening has recently been introduced for men aged 65 years and the reported uptake is 78 per cent. The aim was to determine the impact of a brief intervention on bowel screening in men who attended AAA screening, but previously failed to complete bowel screening.

Methods

Men invited for AAA screening between September 2015 and March 2016 within NHS Tayside were included. Attendees who had not responded to their latest bowel screening invitation were seen by a colorectal cancer clinical nurse specialist. Reasons for not completing the faecal occult blood test (FOBT) were recorded; brief information on colorectal cancer screening was communicated, and participants were offered a further invitation to complete a FOBT. Those who responded positively were sent a further FOBT from the Scottish Bowel Screening Centre. Subsequent return of a completed FOBT within 6 months was recorded.

Results

A total of 556 men were invited for AAA screening, of whom 38·1 per cent had not completed a recent FOBT. The primary reason stated for not participating was the time taken to complete the test or forgetting it (35·1 per cent). Other reasons included: lack of motivation (23·4 per cent), confusion regarding the aim of screening (16·2 per cent), disgust (19·8 per cent), fear (6·3 per cent) and other health problems (9·9 per cent). Following discussion, 81·1 per cent agreed to complete the FOBT and 49 per cent subsequently returned the test.

Conclusion

A substantial proportion of previous bowel screening non-responders subsequently returned a completed FOBT following a brief intervention with a nurse specialist. Attendance at non-bowel screening appointments may provide a valuable opportunity to improve bowel screening uptake.
Comparison of two prognostic models in trauma outcome
Authors: Cook A , Osler T , Glance L , Lecky F , Bouamra O , Weddle J , Gross B , Ward J , Moore F O , Rogers F , Hosmer D
Published: February 2018

Background

The Trauma Audit and Research Network (TARN) in the UK publicly reports hospital performance in the management of trauma. The TARN risk adjustment model uses a fractional polynomial transformation of the Injury Severity Score (ISS) as the measure of anatomical injury severity. The Trauma Mortality Prediction Model (TMPM) is an alternative to ISS; this study compared the anatomical injury components of the TARN model with the TMPM.

Methods

Data from the National Trauma Data Bank for 2011–2015 were analysed. Probability of death was estimated for the TARN fractional polynomial transformation of ISS and compared with the TMPM. The coefficients for each model were estimated using 80 per cent of the data set, selected randomly. The remaining 20 per cent of the data were used for model validation. TMPM and TARN were compared using calibration curves, measures of discrimination (area under receiver operating characteristic curves; AUROC), proximity to the true model (Akaike information criterion; AIC) and goodness of model fit (Hosmer–Lemeshow test).

Results

Some 438 058 patient records were analysed. TMPM demonstrated preferable AUROC (0·882 for TMPM versus 0·845 for TARN), AIC (18 204 versus 21 163) and better fit to the data (32·4 versus 153·0) compared with TARN.

Conclusion

TMPM had greater discrimination, proximity to the true model and goodness-of-fit than the anatomical injury component of TARN. TMPM should be considered for the injury severity measure for the comparative assessment of trauma centres.
Determination of homogentisic acid in urine for diagnosis of alcaptonuria: Capillary electrophoretic method optimization using experimental design
Authors: Öztekin Nevin , Balta Gülfem S. , Cansever M. Şerif
Published: February 2018

Homogentisic acid (HGA) is a diagnostic metabolite that accumulates in the urine and tissues of patients with alkaptonuria which is a rare autosomal recessive disease. HGA is a specific metabolite in urine and serum, which is used for diagnosis of alkaptonuria. This study presents an inexpensive and easy capillary electrophoretic method for the quantitative determination of HGA in urine samples. The method was optimized using full factorial experimental design. The optimal separation electrolyte and separation voltage were revealed as 45 mmol/L phosphate buffer at pH 7.0 and 22 kV, respectively. Under these conditions the presence of HGA was detected in 6 min. Repeatability of migration times and corrected peak areas of HGA (as RSD) were 0.37 and 1.99, respectively. The detection limit was 0.56 μg/mL, 3 times of the average noise, and the quantification limit was 1.85 μg/mL, 10 times the average noise for HGA. Urine samples were directly injected to the capillary without any pretreatment step.
Probing lactate metabolism variations in large‐scale bioreactors
Authors: Xu Sen , Jiang Rubin , Mueller Roland , Hoesli Nadja , Kretz Thomas , Bowers John , Chen Hao
Published: February 2018

Lactate metabolism variations are frequently encountered in mammalian cell culture processes, especially during process scale‐up. In this study, we took a multipronged approach to investigate the impact of pH, pCO2, osmolality, base addition, and mixing conditions on the observed lactate variations in a Chinese Hamster Ovary (CHO) fed‐batch process at 2,000 L scale. Two cultivating methods, CO2‐controlled and pH‐controlled, were used to decouple the individual and synergistic effects from those factors. The individual effects from pH, pCO2, and osmolality on lactate consumption/reproduction in the stationary phase were insignificant in the ranges studied though the initial lactate production rates varied. In contrast, lactate metabolism was found to be impacted by an interaction between mixing conditions and CO2 accumulation. High CO2 accumulation and poor mixing led to lactate reproduction, whereas either low CO2 or improved mixing were sufficient to result in lactate consumption. Base addition was not required for pH control in the low CO2 conditions, and therefore lactate reproduction was correlated with base addition under poor mixing conditions. Under good mixing conditions, CO2‐triggered base addition did not significantly impact lactate reproduction. It is reasonable to postulate that increased mixing times further promoted lactate production during base addition. As lactate reproduction results in more base addition to maintain pH, a cycle could be formed between lactate production and base addition. As a remediation, we showed that such lactate reproduction could be eliminated by improving CO2 removal at 2,000 L scale. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:756–766, 2018
Evaluation of differences between dual salt‐pH gradient elution and mono gradient elution using a thermodynamic model: Simultaneous separation of six monoclonal antibody charge and size variants on preparative‐scale ion exchange chromatographic resin
Authors: Lee Yi Feng , Jöhnck Matthias , Frech Christian
Published: February 2018

The efficiencies of mono gradient elution and dual salt‐pH gradient elution for separation of six mAb charge and size variants on a preparative‐scale ion exchange chromatographic resin are compared in this study. Results showed that opposite dual salt‐pH gradient elution with increasing pH gradient and simultaneously decreasing salt gradient is best suited for the separation of these mAb charge and size variants on Eshmuno® CPX. Besides giving high binding capacity, this type of opposite dual salt‐pH gradient also provides better resolved mAb variant peaks and lower conductivity in the elution pools compared to single pH or salt gradients. To have a mechanistic understanding of the differences in mAb variants retention behaviors of mono pH gradient, parallel dual salt‐pH gradient, and opposite dual salt‐pH gradient, a linear gradient elution model was used. After determining the model parameters using the linear gradient elution model, 2D plots were used to show the pH and salt dependencies of the reciprocals of distribution coefficient, equilibrium constant, and effective ionic capacity of the mAb variants in these gradient elution systems. Comparison of the 2D plots indicated that the advantage of opposite dual salt‐pH gradient system with increasing pH gradient and simultaneously decreasing salt gradient is the noncontinuous increased acceleration of protein migration. Furthermore, the fitted model parameters can be used for the prediction and optimization of mAb variants separation in dual salt‐pH gradient and step elution. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:973–986, 2018
A low‐cost feedback control systems laboratory setup via Arduino–Simulink interface
Authors: Uyanik Ismail , Catalbas Bahadir
Published: February 2018

Control theory education, when supported by practice, becomes more comprehendible for students and useful for their professional career. This paper presents low‐cost experiments for laboratory sessions of a feedback control systems course, which introduces them modeling feedback control systems, proportional‐integral‐derivative (PID) controller design, root locus and Bode plots. The experiments are organized around the Arduino‐based identification and control of a DC motor via Matlab/Simulink. The objective of this laboratory session is to support teaching feedback control systems via experimental investigations on a low‐cost laboratory kit. The built in‐house setups support Arduino–Simulink interface, so that students can download their control diagrams in Simulink to the Arduino board directly. This interface allows students to utilize high level control design tools, such as Matlab/Simulink while working on a low‐cost hardware laboratory setup. Students’ performance in the written exams before and after the laboratory setup were reported to evaluate the instructional effectiveness. Besides, student feedback for four semesters are also presented to evaluate the effectiveness of the laboratory experiments.
Fluorine‐Mediated Editing of a G‐Quadruplex Folding Pathway
Authors: Dickerhoff Jonathan , Weisz Klaus
Published: February 2018

A (3+1)‐hybrid‐type G‐quadruplex was substituted within its central tetrad by a single 2′‐fluoro‐modified guanosine. Driven by the anti‐favoring nucleoside analogue, a novel quadruplex fold with inversion of a single G‐tract and conversion of a propeller loop into a lateral loop emerges. In addition, scalar couplings across hydrogen bonds demonstrate the formation of intra‐ and inter‐residual F⋅⋅⋅H8−C8 pseudo‐hydrogen bonds within the modified quadruplexes. Alternative folding can be rationalized by the impact of fluorine on intermediate species on the basis of a kinetic partitioning mechanism. Apparently, chemical or other environmental perturbations are able to redirect folding of a quadruplex, possibly modulating its regulatory role in physiological processes.
Large Negative Differential Resistance and Rectification from a Donor–σ–Acceptor Molecule in the Presence of Dissimilar Electrodes
Authors: Koley Sayantanu , Chakrabarti Swapan
Published: February 2018

A multifunctional spin quantum device obtained by sandwiching 11‐mercaptoundeca‐2,4,8,10‐tetraenenitrile, a donor–σ–acceptor molecule, between gold and iron electrodes is proposed. The device can act as a spin rectifier at lower bias and also exhibits negative differential resistance (NDR) after attaining a bias of 1.3 V. The rectification feature is quite prominent in the spin‐up channel, with an appreciable rectification ratio of 68, whereas the NDR indicator, that is, the peak to valley ratio (≈10) of the current–voltage characteristics after 1.3 V, is also quite significant. To understand the origin of this in silico observation, nonequilibrium green's function based DFT calculations have been performed. Analyses reveal that both properties originate from the bias‐independent energy offset between the frontier orbitals and electrode Fermi levels, popularly known as Fermi‐level pinning. More precisely, rectification results from the Fermi‐level pinning of the HOMO and LUMO with the gold and iron electrodes, respectively; the Fermi‐level pinning forces a HOMO–LUMO crossover that helps to explain the origin of the NDR.
Synthesis of Palladium Nanoscale Octahedra through a One‐Pot, Dual‐Reductant Route and Kinetic Analysis
Authors: Figueroa‐Cosme Legna , Gilroy Kyle D. , Yang Tung‐Han , Vara Madeline , Park Jinho , Bao Shixiong , da Silva Anderson G. M. , Xia Younan
Published: February 2018

Shape‐controlled synthesis of colloidal metal nanocrystals has traditionally relied on the use of an approach that involves the reduction of a metal precursor by a single reductant. Once the concentration of atoms surpasses supersaturation, they will undergo homogeneous nucleation to generate nuclei and then seeds, followed by further growth into nanocrystals. In general, it is a grand challenge to optimize such an approach because the kinetic requirement for nucleation tends to be drastically different from what is needed to guide the growth process. In this work, we overcome this difficulty by switching to a dual‐reductant approach, in which both strong and weak reductants are added into the same reaction solution. By controlling their amounts to program the reduction kinetics, the strong reductant only regulates the homogeneous nucleation process to generate the desired seeds, and once consumed, the weak reductant takes over to control the growth pattern and thereby the shape of the resulting nanocrystals.
An Adverse Effect of Higher Catalyst Loading and Longer Reaction Time on Enantioselectivity in an Organocatalytic Multicomponent Reaction
Authors: Khopade Tushar M. , Mete Trimbak B. , Arora Jyotsna S. , Bhat Ramakrishna G.
Published: February 2018

An enantioselective organocatalytic multicomponent reaction of aldehydes, ketones, and Meldrum's acid has been developed. A cinchona‐based primary amine (1 mol %) catalyses the multicomponent reaction via the formation of the Knoevenagel product and a chiral enamine to form enantiopure δ‐keto Meldrum's acids in a tandem catalytic pathway. An adverse effect of higher catalyst loading and longer reaction time on enantioselectivity was studied. This mild protocol provides an easy access to enantiopure carboxylic acids, esters and amides and the method is scalable on a gram quantity. DFT calculations were carried out on the proposed reaction mechanism and they were in close agreement with the experimental results.
Crosslinked Egg White as Eco‐Friendly, Reusable, and Cost‐Effective Biosorbent for Rapid Removal of Indigo Carmine
Authors: Oymak Tulay , Bağda Esra
Published: February 2018

In the present study, crosslinked egg white is used as a low‐cost biosorbent for removal of a toxic dye, indigo carmine. The biosorbent preparation is easy and only N,N′‐methylenebis(acrylamide) is added for crosslinking. The characterization of the prepared material is done with scanning electron microscopy and IR spectroscopy. The surface charge is determined with point of zero charge method. The prepared biosorbent is used for removal of indigo carmine. The experimental parameters (e.g., pH of solution, initial dye concentration, time) are optimized to achieve quantitative removal. The biosorption data of indigo carmine on crosslinked egg white is fitted with the Langmuir model with a Qmax value of 67.56 mg g−1. The kinetic data are treated with pseudo‐first‐ and second‐order models. The second‐order model best explains the kinetic behavior of the process. The quantitative extraction of indigo carmine is achieved for 25 mg g−1 of IC within 30 min at pH 2. The crosslinked egg white can be used several times after regeneration.
TGFβ1‐induced expression of caldesmon mediates epithelial–mesenchymal transition
Authors: Nalluri Sandeep M. , O'Connor Joseph W. , Virgi Gage A. , Stewart Samantha E. , Ye Dan , Gomez Esther W.
Published: February 2018

Epithelial–mesenchymal transition (EMT) is an important process that mediates organ development and wound healing, and in pathological contexts, it can contribute to the progression of fibrosis and cancer. During EMT, cells exhibit marked changes in cytoskeletal organization and increased expression of a variety of actin associated proteins. Here, we sought to determine the role of caldesmon in mediating EMT in response to transforming growth factor (TGF)‐β1. We find that the expression level and phosphorylation state of caldesmon increase as a function of time following induction of EMT by TGFβ1 and these changes in caldesmon correlate with increased focal adhesion number and size and increased cell contractility. Knockdown and forced expression of caldesmon in epithelial cells reveals that caldesmon expression plays an important role in regulating the expression of the myofibroblast marker alpha smooth muscle actin. Results from these studies provide insight into the role of cytoskeletal associated proteins in the regulation of EMT and may suggest ways to target the cell cytoskeleton for regulating EMT processes.
Neuregulin directed molecular mechanisms of visual cortical plasticity
Authors: Grieco Steven F. , Holmes Todd C. , Xu Xiangmin
Published: February 2018

Experience‐dependent critical period (CP) plasticity has been extensively studied in the visual cortex. Monocular deprivation during the CP affects ocular dominance, limits visual performance, and contributes to the pathological etiology of amblyopia. Neuregulin‐1 (NRG1) signaling through its tyrosine kinase receptor ErbB4 is essential for the normal development of the nervous system and has been linked to neuropsychiatric disorders such as schizophrenia. We discovered recently that NRG1/ErbB4 signaling in PV neurons is critical for the initiation of CP visual cortical plasticity by controlling excitatory synaptic inputs onto PV neurons and thus PV‐cell mediated cortical inhibition that occurs following visual deprivation. Building on this discovery, we review the existing literature of neuregulin signaling in developing and adult cortex and address the implication of NRG/ErbB4 signaling in visual cortical plasticity at the cellular and circuit levels. NRG‐directed research may lead to therapeutic approaches to reactivate plasticity in the adult cortex.
Pharmacogenetic Information in Clinical Guidelines: The European Perspective
Authors: Swen Jesse J. , Nijenhuis Marga , van Rhenen Mandy , de Boer‐Veger Nienke J. , Buunk Anne‐Marie , Houwink Elisa J.F. , Mulder Hans , Rongen Gerard A. , van Schaik Ron H.N. , van der Weide Jan , Wilffert Bob , Deneer Vera H.M. , Guchelaar Henk‐Jan ,   on behalf of the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Pharmacists Association (KNMP)
Published: February 2018

Surveys among pharmacists and physicians show that these healthcare professionals have successfully adopted the concept of pharmacogenomics (PGx).1‐3 In addition, patients are willing to consent to participate in PGx implementation studies.4 However, the surveys also show that healthcare professionals do not frequently order or recommend a PGx test.1,2 Among others, a frequently perceived hurdle for clinical uptake of PGx is the availability of guidelines translating PGx test results into clinical actions for individual patients.5,6
Estimating dispersal in spatiotemporally variable environments using multievent capture–recapture modeling
Authors: Cayuela Hugo , Pradel Roger , Joly Pierre , Bonnaire Eric , Besnard Aurélien
Published: February 2018

Dispersal is a key process in ecological and evolutionary dynamics. Spatiotemporal variation in habitat availability and characteristics has been suggested to be one of the main cause involved in dispersal evolution and has a strong influence on metapopulation dynamics. In recent decades, the study of dispersal has led to the development of capture–recapture (CR) models that allow movement between sites to be quantified, while handling imperfect detection. For studies involving numerous recapture sites, Lagrange et al. () proposed a multieventCRmodel that allows dispersal to be estimated while omitting site identity by distinguishing between individuals that stay and individuals that move. More recently, Cayuela et al. () extended this model to allow survival and dispersal probabilities to differ for the different types of habitat represented by several sites within a study area. Yet in both of these modeling systems, the state of sites is assumed to be static over time, which is not a realistic assumption in dynamic landscapes. For that purpose, we generalized the multieventCRmodel proposed by Cayuela et al. () to allow the estimation of dispersal, survival and recapture probabilities when a site may appear or disappear over time (MODEL1) or when the characteristics of a site fluctuate over space and time (MODEL2). This paper first presents these two new modeling systems, and then provides an illustration of their efficacy and usefulness by applying them to simulatedCRdata and data collected on two metapopulations of amphibians.MODEL1 was tested usingCRdata recorded on a metapopulation of yellow‐bellied toads (Bombina variegata). In this first empirical case, we examined whether the drying‐out dynamics of ponds and the past dispersal status of an individual might affect dispersal behavior. Our study revealed that the probability of facultative dispersal (i.e., from a pond group that remained available/flooded) fluctuated between years and was higher in individuals that had previously dispersed.MODEL2 was tested usingCRdata collected on a metapopulation of great crested newts (Triturus cristatus). In this second empirical example, we investigated whether the density of alpine newts (Ichthyosaura alpestris), a potential competitor, might affect the dispersal and survival of the crested newt. Our study revealed that the departure rate was lower in ponds with a high density of heterospecifics than in ponds with a low density of heterospecifics at both inter‐annual and intra‐annual scales. Moreover, annual survival was slightly higher in ponds with a high density of heterospecifics. Overall, our findings indicate that these multieventCRmodels provide a highly flexible means of modeling dispersal in dynamic landscapes.
Insights into implementation of sacubitril/valsartan into clinical practice
Authors: Martens Pieter , Beliën Hanne , Dupont Matthias , Mullens Wilfried
Published: February 2018

Background

Sacubitril/valsartan significantly reduced heart failure hospitalization and mortality in PARADIGM‐HF (Prospective Comparison of Angiotensin Receptor‐Neprilysin Inhibitor With an Angiotensin‐Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure). However, real‐world data from its use are lacking.

Methods and results

We retrospectively assessed all baseline and follow‐up data of consecutive heart failure patients with reduced ejection fraction receiving therapy with sacubitril/valsartan for Class I recommendation between December 2016 and July 2017. Baseline characteristics and dose titration of sacubitril/valsartan were compared between patients in clinical practice and in PARADIGM‐HF. A total of 120 patients (81% male) were switched from angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. A total of 20.1% of patients received dose uptitration. Patients were treated with an equipotential dose of renin–angiotensin system blockers before and after uptitration of sacubitril/valsartan (57 ± 29% vs. 53 ± 29% of target dose indicated by European Society of Cardiology guidelines; P = 0.286). However, they received a lower dose of sacubitril/valsartan in comparison with those in the PARADIGM‐HF (219 ± 12 vs. 375 ± 75 mg; P < 0.001). In comparison with the patients receiving sacubitril/valsartan in PARADIGM‐HF, patients in clinical practice were older and had a higher serum creatinine, higher New York Heart Association functional classification, and lower left ventricular ejection fraction (all P‐value <0.05). Even in comparison with patients who experienced dropout during the run‐in phase of PARADIGM‐HF, real‐world patients exhibited baseline characteristics indicative of more disease severity. Patients were at high absolute baseline risk for adverse outcome as illustrated by the EMPHASIS‐HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk score of 6 (inter‐quartile range 3), in comparison with 5 (inter‐quartile range 4) in PARADIGM‐HF. After initiation of sacubitril/valsartan, New York Heart Association class significantly improved (P < 0.001), but systolic blood pressure dropped more than was reported in PARADIGM‐HF (7.1 ± 8.0 vs. 3.2 ± 0.4 mmHg; P < 0.001).

Conclusions

Patients in clinical practice exhibit baseline characteristics associated with more severe disease, which might lead to prescription of lower doses. Nevertheless, patients in clinical practice are at high risk of adverse outcome as illustrated by the EMPHASIS‐HF risk score, underscoring the large potential for sacubitril/valsartan therapy to reduce the risk of heart failure hospitalization and all‐cause mortality.
Association between sleep‐disordered breathing and arterial stiffness in heart failure patients with reduced or preserved ejection fraction
Authors: Suzuki Satoshi , Yoshihisa Akiomi , Sato Yu , Watanabe Shunsuke , Yokokawa Tetsuro , Sato Takamasa , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Kunii Hiroyuki , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu‐ichi , Ishida Takafumi , Takeishi Yasuchika
Published: February 2018

Aims

Sleep‐disordered breathing (SDB) is associated with arterial stiffness, which may be one of the factors that lead to heart failure (HF). We examined the relationship between pulse wave velocity (PWV) and SDB in patients who have HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).

Methods and results

We measured the apnoea–hypopnoea index (AHI) by polysomnography, echocardiographic parameters, and PWV in 221 HF patients. Age, blood pressure, and PWV were higher in HFpEF (ejection fraction > 50%, n = 70) patients than in HFrEF (ejection fraction < 50%, n = 151) patients. All HF patients were divided into three groups according to AHI: none‐to‐mild SDB group (AHI < 15 times/h, n = 77), moderate SDB group (15 < AHI < 30 times/h, n = 59), and severe SDB group (AHI > 30 times/h, n = 85). Although blood pressure and echocardiographic parameters did not differ among the three groups, PWV was significantly higher in the severe SDB group than in the none‐to‐mild and moderate SDB groups (P = 0.002). When the HFrEF and HFpEF patients were analysed separately, PWV was significantly higher in the severe SDB group than in the none‐to‐mild and moderate SDB groups in patients with HFpEF (P = 0.002), but not in those with HFrEF (P = 0.068). In the multiple regression analysis to determine PWV, the presence of severe SDB was found to be an independent predictor of high PWV in HFpEF (β = 0.234, P = 0.005), but not in HFrEF patients.

Conclusions

Severe SDB is associated with elevated arterial stiffness and may be related to the pathophysiology of HF, especially in HFpEF patients.
Chloroquine‐induced cardiomyopathy: a reversible cause of heart failure
Authors: Yogasundaram Haran , Hung Whitney , Paterson Ian D. , Sergi Consolato , Oudit Gavin Y.
Published: February 2018

Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti‐rheumatic medications frequently used in the treatment of connective tissue disorders. We present the case of a 45‐year‐old woman with CQ‐induced cardiomyopathy leading to severe heart failure. Electrocardiographic abnormalities included bifascicular block, while structural disease consisted of severe biventricular and biatrial hypertrophy. Appropriate diagnosis via endomyocardial biopsy led to cessation of CQ and subsequent dramatic improvement in symptoms and structural heart disease. Cardiac toxicity is an under‐recognized adverse effect of CQ/HCQ leading to cardiomyopathy with concentric hypertrophy and conduction abnormalities, with the potential for significant morbidity and mortality. Predisposing factors for CQ/HCQ‐induced cardiomyopathy have been proposed. CQ/HCQ cardiomyopathy is a phenocopy of Fabry disease, and α‐galactosidase A polymorphism may account for some heterogeneity of disease presentation.