bluuebunny/crossref_metadata_2025 huggingface dataset:
White matter mean diffusivity correlates with myelination in tuberous sclerosis complex
Authors: Peters Jurriaan M. , Struyven Robbert R. , Prohl Anna K. , Vasung Lana , Stajduhar Andrija , Taquet Maxime , Bushman John J. , Lidov Hart , Singh Jolene M. , Scherrer Benoit , Madsen Joseph R. , Prabhu Sanjay P. , Sahin Mustafa , Afacan Onur , Warfield Simon K.
Published: June 2019

Objective

Diffusion tensor imaging (DTI) of the white matter is a biomarker for neurological disease burden in tuberous sclerosis complex (TSC). To clarify the basis of abnormal diffusion in TSC, we correlated ex vivo high‐resolution diffusion imaging with histopathology in four tissue types: cortex, tuber, perituber, and white matter.

Methods

Surgical specimens of three children with TSC were scanned in a 3T or 7T MRI with a structural image isotropic resolution of 137–300 micron, and diffusion image isotropic resolution of 270‐1,000 micron. We stained for myelin (luxol fast blue, LFB), gliosis (glial fibrillary acidic protein, GFAP), and neurons (NeuN) and registered the digitized histopathology slides (0.686 micron resolution) to MRI for visual comparison. We then performed colocalization analysis in four tissue types in each specimen. Finally, we applied a linear mixed model (LMM) for pooled analysis across the three specimens.

Results

In white matter and perituber regions, LFB optical density measures correlated with fractional anisotropy (FA) and inversely with mean diffusivity (MD). In white matter only, GFAP correlated with MD, and inversely with FA. In tubers and in the cortex, there was little variation in mean LFB and GFAP signal intensity, and no correlation with MRI metrics. Neuronal density correlated with MD. In the analysis of the combined specimens, the most robust correlation was between white matter MD and LFB metrics.

Interpretation

In TSC, diffusion imaging abnormalities in microscopic tissue types correspond to specific histopathological markers. Across all specimens, white matter diffusivity correlates with myelination.
Ribonucleoprotein: A Biomimetic Platform for Targeted siRNA Delivery
Authors: Tai Wanyi , Gao Xiaohu
Published: June 2019

Many small interfering RNA (siRNA) carriers have been developed over the years, mostly based on cationic lipids and polymers that can condense siRNA into nanoparticle complexes and aid in endosomal escape. In comparison, development of charge‐neutral siRNA carriers to avoid or reduce nonspecific binding, aggregation, and toxicity is limited, due to a lack of mechanisms for carrier‐siRNA association beyond electrostatic interaction. Here, a unique, charge‐neutral, biomimetic platform is reported, mimicking the natural state of functional RNA, ribonucleoprotein (RNP). This RNP architecture is simple to make, precise in assembly stoichiometry, stable in serum, and biocompatible. Gene knockdown is achieved in vitro and in vivo, demonstrating excellent potential for translation.
Solid–Liquid Triboelectrification Control and Antistatic Materials Design Based on Interface Wettability Control
Authors: Li Xiaojuan , Zhang Liqiang , Feng Yange , Zhang Xiaolong , Wang Daoai , Zhou Feng
Published: June 2019

Solid–liquid contact triboelectrification has been a hot and important topic due to its severe electrostatic hazards in the petroleum industry and its positive potential application in energy harvesting. Here, the influence of surface structure, composition, and interfacial wettability on the solid–liquid triboelectrification basing on the friction of polypropylene (PP) films and deionized water is systematically studied. PP films with different nanowire structures are prepared by a hot pressing method with varied anodic aluminum oxide as templates. The PP films are surface functionalized with three different functional groups by a surface self‐assembly technology. The results show that compared with the surface structure, the solid–liquid triboelectrification is more sensitive to the surface components. While from the macroscopic view the interfacial wettability plays a dominant role in its electrical output, with the failure of the hydrophobic surface of the PP film, the triboelectrical output continues to deteriorate. Moreover, the increase or decrease of solid–liquid triboelectrification can be achieved by controlling the structure or composition. This study demonstrates the possibility of adjusting the solid–liquid contact electrification in a controllable manner and provides a basis for the utilization or the prevention of solid–liquid friction charges.
Biomimetic Omnidirectional Antireflective Glass via Direct Ultrafast Laser Nanostructuring
Authors: Papadopoulos Antonis , Skoulas Evangelos , Mimidis Alexandros , Perrakis George , Kenanakis George , Tsibidis George D. , Stratakis Emmanuel
Published: June 2019

Here, a single‐step, biomimetic approach for the realization of omnidirectional transparent antireflective glass is reported. In particular, it is shown that circularly polarized ultrashort laser pulses produce self‐organized nanopillar structures on fused silica (SiO2). The laser‐induced nanostructures are selectively textured on the glass surface in order to mimic the spatial randomness, pillar‐like morphology, as well as the remarkable antireflection properties found on the wings of the glasswing butterfly, Greta oto, and various Cicada species. The artificial structures exhibit impressive antireflective properties, both in the visible and infrared frequency ranges, which are remarkably stable over time. Accordingly, the laser‐processed glass surfaces show reflectivity smaller than 1% for various angles of incidence in the visible spectrum for s–p linearly polarized configurations. However, in the near‐infrared spectrum, the laser‐textured glass shows higher transmittance compared to the pristine. It is envisaged that the current results will revolutionize the technology of antireflective transparent surfaces and impact numerous applications from glass displays to optoelectronic devices.
Optical Nanomaterials and Enabling Technologies for High‐Security‐Level Anticounterfeiting
Authors: Ren Wei , Lin Gungun , Clarke Christian , Zhou Jiajia , Jin Dayong
Published: June 2019

Optical nanomaterials have been widely used in anticounterfeiting applications. There have been significant developments powered by recent advances in material science, printing technologies, and the availability of smartphone‐based decoding technology. Recent progress in this field is surveyed, including the availability of optical reflection, absorption, scattering, and luminescent nanoparticles. It is demonstrated that advances in the design and synthesis of lanthanide‐doped upconversion nanoparticles will lead to the next generation of anticounterfeiting technologies. Their tunable optical properties and optical responses to a range of external stimuli allow high‐security level information encoding. Challenges in the scale‐up synthesis of nanomaterials, engineering of assessorial devices for smart‐phone‐based decryption, and alignment to the potential markets which will lead to new directions for research, are discussed.
Rare‐Earth‐Element‐Ytterbium‐Substituted Lead‐Free Inorganic Perovskite Nanocrystals for Optoelectronic Applications
Authors: Moon Byung Joon , Kim Sang Jin , Lee Seungmin , Lee Aram , Lee Hyunjung , Lee Dong Su , Kim Tae‐Wook , Lee Seoung‐Ki , Bae Sukang , Lee Sang Hyun
Published: June 2019

Lead‐(Pb‐) halide perovskite nanocrystals (NCs) are interesting nanomaterials due to their excellent optical properties, such as narrow‐band emission, high photoluminescence (PL) efficiency, and wide color gamut. However, these NCs have several critical problems, such as the high toxicity of Pb, its tendency to accumulate in the human body, and phase instability. Although Pb‐free metal (Bi, Sn, etc.) halide perovskite NCs have recently been reported as possible alternatives, they exhibit poor optical and electrical properties as well as abundant intrinsic defect sites. For the first time, the synthesis and optical characterization of cesium ytterbium triiodide (CsYbI3) cubic perovskite NCs with highly uniform size distribution and high crystallinity using a simple hot‐injection method are reported. Strong excitation‐independent emission and high quantum yields for the prepared NCs are verified using photoluminescence measurements. Furthermore, these CsYbI3 NCs exhibit potential for use in organic–inorganic hybrid photodetectors as a photoactive layer. The as‐prepared samples exhibit clear on–off switching behavior as well as high photoresponsivity (2.4 × 103 A W−1) and external quantum efficiency (EQE, 5.8 × 105%) due to effective exciton dissociation and charge transport. These results suggest that CsYbI3 NCs offer tremendous opportunities in electronic and optoelectronic applications, such as chemical sensors, light emitting diodes (LEDs), and energy conversion and storage devices.
Fabrication of High‐Performance Silver Mesh for Transparent Glass Heaters via Electric‐Field‐Driven Microscale 3D Printing and UV‐Assisted Microtransfer
Authors: Zhu Xiaoyang , Xu Quan , Li Hongke , Liu Mingyang , Li Zhenghao , Yang Kun , Zhao Jiawei , Qian Lei , Peng Zilong , Zhang Guangming , Yang Jianjun , Wang Fei , Li Dichen , Lan Hongbo
Published: June 2019

Great challenges remain concerning the cost‐effective manufacture of high‐performance metal meshes for transparent glass heaters (TGHs). Here, a high‐performance silver mesh fabrication technique is proposed for TGHs using electric‐field‐driven microscale 3D printing and a UV‐assisted microtransfer process. The results show a more optimal trade‐off in sheet resistance (Rs = 0.21 Ω sq−1) and transmittance (T = 93.9%) than for indium tin oxide (ITO) and ITO substitutes. The fabricated representative TGH also exhibits homogeneous and stable heating performance, remarkable environmental adaptability (constant Rs for 90 days), superior mechanical robustness (Rs increase of only 0.04 in harsh conditions–sonication at 100 °C), and strong adhesion force with a negligible increase in Rs (2–12%) after 100 peeling tests. The practical viability of this TGH is successfully demonstrated with a deicing test (ice cube: 21 cm3, melting time: 78 s, voltage and glass thickness: 4 V, 5 mm). All of these advantages of the TGHs are attributed to the successful fabrication of silver meshes with high resolution and high aspect ratio on the glass substrate using the thick film silver paste. The proposed technique is a promising new tool for the inexpensive fabrication of high‐performance TGHs.
Recent Trends in the Silver‐Catalyzed Synthesis of Nitrogen Heterocycles
Authors: Sreedevi Radhakrishnan , Saranya Salim , Anilkumar Gopinathan
Published: June 2019

Heterocycles are generally biologically active compounds and are the main basic scaffolds in many natural and non‐natural moieties. Recently, silver‐catalyzed syntheses have undergone remarkable progress in the field of synthetic heterocyclic chemistry. This review summarizes the recent trends in the silver‐catalyzed synthesis of nitrogen‐containing heterocyclic compounds.

magnified image
14.1% CsPbI3 Perovskite Quantum Dot Solar Cells via Cesium Cation Passivation
Authors: Ling Xufeng , Zhou Sijie , Yuan Jianyu , Shi Junwei , Qian Yuli , Larson Bryon W. , Zhao Qian , Qin Chaochao , Li Fangchao , Shi Guozheng , Stewart Connor , Hu Jiaxin , Zhang Xuliang , Luther Joseph M. , Duhm Steffen , Ma Wanli
Published: June 2019

Surface manipulation of quantum dots (QDs) has been extensively reported to be crucial to their performance when applied into optoelectronic devices, especially for photovoltaic devices. In this work, an efficient surface passivation method for emerging CsPbI3 perovskite QDs using a variety of inorganic cesium salts (cesium acetate (CsAc), cesium idodide (CsI), cesium carbonate (Cs2CO3), and cesium nitrate (CsNO3)) is reported. The Cs‐salts post‐treatment can not only fill the vacancy at the CsPbI3 perovskite surface but also improve electron coupling between CsPbI3 QDs. As a result, the free carrier lifetime, diffusion length, and mobility of QD film are simultaneously improved, which are beneficial for fabricating high‐quality conductive QD films for efficient solar cell devices. After optimizing the post‐treatment process, the short‐circuit current density and fill factor are significantly enhanced, delivering an impressive efficiency of 14.10% for CsPbI3 QD solar cells. In addition, the Cs‐salt‐treated CsPbI3 QD devices exhibit improved stability against moisture due to the improved surface environment of these QDs. These findings will provide insight into the design of high‐performance and low‐trap‐states perovskite QD films with desirable optoelectronic properties.
Lithiophilic CuO Nanoflowers on Ti‐Mesh Inducing Lithium Lateral Plating Enabling Stable Lithium‐Metal Anodes with Ultrahigh Rates and Ultralong Cycle Life
Authors: Huang Kai , Li Zhi , Xu Qunjie , Liu Haimei , Li Hexing , Wang Yonggang
Published: June 2019

Lithium (Li) metal anodes are promising candidates for high‐energy‐density batteries. However, uncontrollable dendritic plating behavior and infinite volume expansion are hindering their practical applications. Herein, a novel CuO@Ti‐mesh (CTM) is prepared by microwave‐assisted reactions, followed by pressing on Li wafers, leading to Li/CuO@Ti‐mesh (LCTM) composite anodes. The lithiophilic CuO nanoflowers on Ti‐mesh provides evenly distributed nucleation sites, inducing uniform Li‐ion lateral plating, which can effectively inhibit the growth of Li dendrites and volume expansion during cycling. The as‐prepared LCTM composite anode exhibits high Coulombic efficiency (CE) of 94.2% at 10 mA cm‐2 over 90 cycles. Meanwhile, the LCTM anode shows a low overpotential of 50 mV at 10 mA cm‐2 over 16 000 cycles and a low overpotential of 90 and 250 mV even at ultrahigh current densities of 20 and 40 mA cm‐2. When paired with Li4Ti5O12 (LTO), it enhances the capacity retention of LTO/Li wafer full cells by about two times from 36.6% to 73.0% and 42.0% to 80.0% at 5C and 10C with long‐term cycling. It is hoped that this LCTM anode with ultrahigh rates and ultralong cycle life may put Li‐metal anode forward to practical applications, such as in Li–S, Li‐air batteries, etc.
A High‐Performance Monolithic Solid‐State Sodium Battery with Ca2+ Doped Na3Zr2Si2PO12 Electrolyte
Authors: Lu Yao , Alonso Jose A. , Yi Qiang , Lu Liang , Wang Zhong Lin , Sun Chunwen
Published: June 2019

Solid‐state sodium batteries (SSSBs) are promising electrochemical energy storage devices due to their high energy density, high safety, and abundant resource of sodium. However, low conductivity of solid electrolyte as well as high interfacial resistance between electrolyte and electrodes are two main challenges for practical application. To address these issues, pure phase Na3Zr2Si2PO12 (NZSP) materials with Ca2+ substitution for Zr4+ are synthesized by a sol‐gel method. It shows a high ionic conductivity of more than 10−3 S cm−1 at 25 °C. Moreover, a robust SSSB is developed by integrating sodium metal anodes into NZSP‐type monolithic architecture, forming a 3D electronic and ionic conducting network. The interfacial resistance is remarkably reduced and the monolithic symmetric cell displays stable sodium platting/striping cycles with low polarization for over 600 h. Furthermore, by combining sodium metal anode with Na3V2(PO4)3 cathode, an SSSB is demonstrated with high rate capability and excellent cyclability. After 450 cycles, the capacity of the cell is still kept at 94.9 mAh g−1 at 1 C. This unique design of monolithic electrolyte architecture provides a promising strategy toward realizing high‐performance SSSBs.
A Fully Reversible Water Electrolyzer Cell Made Up from FeCoNi (Oxy)hydroxide Atomic Layers
Authors: Zhang Qingran , Bedford Nicholas M. , Pan Jian , Lu Xunyu , Amal Rose
Published: June 2019

Renewable electricity powered water electrolysis is a promising solution for the conversion and storage of the intermittent renewable energy resources in the form of hydrogen. Herein, atomically thin FeCoNi ternary (oxy)hydroxide nanosheets (FeCoNi‐ATNs) are developed as efficient and robust bifunctional electrocatalysts for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in 1 m KOH solution (pH = 14). The electrocatalyst shows remarkably high apparent catalytic performance (400 mA cm−2 at 350 mV for OER and 240 mV for HER) and mass activities at modest overpotentials (1931 A g−1 at 330 mV for OER; 1819 A g−1 at 200 mV for HER). Moreover, the OER and HER performance of FeCoNi–ATNs are fully reversible and electrochemically switchable, due to the interconversion attribute of two catalytic states for OER and HER. Using the dual functional properties of this catalyst, a fully reversible water electrolyzer cell is fabricated, exhibiting a robust reversibility between two half reactions in water electrolysis under a high current density (100 mA cm−1), which can effectively overcome the stability issues caused by electrode depolarization during frequent power interruptions, an inevitable phenomenon commonly brought about by the usage of intermittent renewable energy supplies.
Realizing High‐Ranged Out‐of‐Plane ZTs in N‐Type SnSe Crystals through Promoting Continuous Phase Transition
Authors: Chang Cheng , Wang Dongyang , He Dongsheng , He Wenke , Zhu Fangyuan , Wang Guangtao , He Jiaqing , Zhao Li‐Dong
Published: June 2019

Thermoelectric technology enables direct conversion between heat and electricity. The conversion efficiency of a thermoelectric device is determined by the average dimensionless figure of merit ZTave. Here, a record high ZTave of ≈1.34 in the range of 300–723 K in n‐type SnSe based crystals is reported. The remarkable thermoelectric performance derives from the high power factor and the reduced thermal conductivity in the whole temperature range. The high power factor is realized by promoting the continuous phase transition in SnSe crystals through alloying PbSe, which results in a higher symmetry of the crystal structure and the correspondingly modified electronic band structure. Moreover, PbSe alloying induces mass and strain fluctuations, which enables the suppression of thermal transport. These findings provide a new strategy to enhance the thermoelectric performance for the continuous phase transition materials.
In vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin
Authors: Hedges Jason B. , Ryan Katherine S.
Published: June 2019

Nitroimidazoles are one of the most effective ways to treat anaerobic bacterial infections. Synthetic nitroimidazoles are inspired by the structure of azomycin, isolated from Streptomyces eurocidicus in 1953. Despite its foundational role, no biosynthetic gene cluster for azomycin has been found. Guided by bioinformatics, we identified a cryptic biosynthetic gene cluster in Streptomyces cattleya and then carried out in vitro reconstitution to deduce the enzymatic steps in the pathway linking l‐arginine to azomycin. The gene cluster we discovered is widely distributed among soil‐dwelling actinobacteria and proteobacteria, suggesting that azomycin and related nitroimidazoles may play important ecological roles. Our work sets the stage for development of biocatalytic approaches to generate azomycin and related nitroimidazoles.
Polybenzimidazole as proton conducting filler in polydimethylsiloxane: Enhanced oxidative stability and membrane properties
Authors: Satheesh Kumar B. , Sana Balakondareddy , Unnikrishnan G. , Jana Tushar , Santhosh Kumar K. S.
Published: June 2019

In this work, pyridine‐based low‐molecular‐weight polybenzimidazole (LMP) was synthesized (inherent viscosity: 0.52 dL g−1) by controlling the reaction time. The synthesized LMP was incorporated into polydimethylsiloxane (PDMS) matrix to impart proton conductivity. The composite membrane containing 30 wt % of LMP exhibited proton conductivity of 16 mS cm−1 at 100–120 °C. The LMP chains were bundled and formed clusters (aggregates) in the PDMS matrix as observed in field emission scanning electron microscopy. This is attributed to nonpolar (siloxane)–polar (polybenzimidazole) repulsion. An impressive weight loss of 8.6% was observed after 120 h Fenton's test that indicates the high oxidative stability of composite membranes. However, elongation of composite membranes was decreased compared to that of pristine PDMS, which is attributed to the incorporation of rigid LMP chains. The resultant composite membranes exhibited moderate proton conductivity, low moisture absorption, and good thermal stability. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48151.
Preparation of regenerated silk fibroin‐based heat‐management sponge for wound healing
Authors: Li Yu , Zhao Liang , Wang Hao , Li Baohua
Published: June 2019

In the present study, a regenerated silk fibroin (RSF) sponge incorporated with the phase change microcapsules were synthesized by facile and effective routes. The microcapsules with the phase change materials (PCMs) core and the RSF wall were prepared by simple coacervation. By altering the synthesis parameters including the emulsifier concentration and the RSF concentration, the microcapsules exhibiting optimized spherical geometry, high encapsulation efficiency, high phase change enthalpies, good thermal cycling performance, and high thermal stability were synthesized. As to the preparation of the microstructurally aligned RSF sponge, a new type of freeze–thaw method was used for the first time, the resultant sponge exhibited high elastic resilience. Subsequently, the combination of microcapsules with the RSF sponge was achieved by a convenient deposition method with the aid of ultrasonic agitation, which showed well maintained porous structure and satisfactory phase change enthalpies of 23.16 and 23.32 J•g−1 corresponding to the heating and cooling process, respectively. Therefore, the PCMs‐incorporated RSF sponge exhibited the capacity to regulate the temperature in order to create a stable “microclimate.” Regarding the exceptional biocompatibility, biodegradability, and super comfort of RSF materials, the RSF‐based sponge can be an ideal candidate for wound dressing applications. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48173.
Optical variability of blazars
Authors: Abrahamyan H. V. , Mickaelian Areg M. , Paronyan G. M. , Mikayelyan G. A.
Published: June 2019

The analysis of blazars' parameters from BZCAT leads to a conclusion that they do not have the same properties. The preliminary criterion to include an object in the catalog was the strong radio emission; however, two type of radio sources were selected: BL Lacertae (BLL) objects and Flat Spectrum Radio Quasars (FSRQ). As a number of properties are typical of blazars (strong radio emission, optical variability, continuum optical spectra, polarization, high luminosity, etc.), using the optical data, we investigate them to clarify which property plays the most significant role in their classification as blazars. We found that 60% of blazars have optical variability. We use a technique developed based on POSS1 and POSS2 photometry and group the variability into extreme, strong, medium, and low classes. In the optical range, 51 blazars have powerful variability (extreme variables), and 126 are high variables. In addition, 63% of blazars have detected radiation in X‐ray and 28% have detected radiation in gamma rays. We give the average statistical characteristics of blazars based on our analysis and calculations.
Improving Product Specificity of Whole‐Cell Alkane Oxidation in Nonconventional Media: A Multivariate Analysis Approach
Authors: Kolmar Johannes F. , Thum Oliver , Baganz Frank
Published: June 2019

Two‐liquid‐phase reaction media have long been used in bioconversions to supply or remove hydrophobic organic reaction substrates and products to reduce inhibitory and toxic effects on biocatalysts. In case of the terminal oxyfunctionalization of linear alkanes by the AlkBGT monooxygenase the excess alkane substrate is often used as a second phase to extract the alcohol, aldehyde, and acid products. However, the selection of other carrier phases or surfactants is complex due to a large number of parameters that are involved, such as biocompatibility, substrate bioavailability, and product extraction selectivity. This study combines systematic high‐throughput screening with chemometrics to correlate physicochemical parameters of a range of cosolvents to product specificity and yield using a multivariate regression model. Partial least‐squares regression shows that the defining factor for product specificity is the solubility properties of the reaction substrate and product in the cosolvent, as measured by Hansen solubility parameters. Thus the polarity of cosolvents determines the accumulation of either alcohol or acid products. Whereas usually the acid product accumulates during the reaction, by choosing a more polar cosolvent the 1‐alcohol product can be accumulated. Especially with Tergitol as a cosolvent, a 3.2‐fold improvement in the 1‐octanol yield to 18.3  mmol  L−1 is achieved relative to the control reaction without cosolvents.
Microbioreactor Cultivations of Fab‐Producing Escherichia coli Reveal Genome‐Integrated Systems as Suitable for Prospective Studies on Direct Fab Expression Effects
Authors: Fink Mathias , Vazulka Sophie , Egger Esther , Jarmer Johanna , Grabherr Reingard , Cserjan‐Puschmann Monika , Striedner Gerald
Published: June 2019

Despite efforts to develop concepts for efficient antibody fragment (Fab) production in Escherichia coli (E. coli) and the high degree of similarity within this protein class, a generic platform technology is still not available. Indeed, feasible production of new Fab candidates remains challenging. In this study, a setup that enables direct characterization of host cell response to Fab expression by utilizing genome‐integrated (GI) systems is established. Among the multitude of factors that influence Fab expression, the variable domain, the translocation mechanism, the host strain, as well as the copy number of the gene of interest (GOI) are varied. The resulting 32 production clones are characterized in carbon‐limited microbioreactor cultivations with yields of 0–7.4 mg Fab per gram of cell dry mass. Antigen‐binding region variations have the greatest effect on Fab yield. In most cases, the E. coli HMS174(DE3) strain performs better than the BL21(DE3) strain. Translocation mechanism variations mainly influence leader peptide cleavage efficiency. Plasmid‐free systems, with a single copy of the GOI integrated into the chromosome, reach Fab yields in the range of 80–300% of plasmid‐based counterparts. Consequently, the GI Fab production clones could greatly facilitate direct analyses of systems response to different impact factors under varying production conditions.
A machine‐learning approach to calibrate generic Raman models for real‐time monitoring of cell culture processes
Authors: Tulsyan Aditya , Schorner Gregg , Khodabandehlou Hamid , Wang Tony , Coufal Myra , Undey Cenk
Published: June 2019

The manufacture of biotherapeutic proteins consists of complex upstream unit operations requiring multiple raw materials, analytical techniques, and control strategies to produce safe and consistent products for patients. Raman spectroscopy is a ubiquitous multipurpose analytical technique in biopharmaceutical manufacturing for real‐time predictions of critical parameters in cell culture processes. The accuracy of Raman spectroscopy relies on chemometric models that need to be carefully calibrated. The existing calibration procedure is nontrivial to implement as it necessitates executing multiple carefully designed experiments for generating relevant calibration sets. Further, existing procedure yields calibration models that are reliable only in operating conditions they were calibrated in. This creates a unique challenge in clinical manufacturing where products have limited production history. In this paper, a novel machine‐learning procedure based on just‐in‐time learning (JITL) is proposed to calibrate Raman models. Unlike traditional techniques, JITL‐based generic Raman models can be reliably used for different modalities, cell lines, culture media, and operating conditions. The accuracy of JITL‐based generic models is demonstrated on several validation studies involving real‐time predictions of critical cell culture performance parameters, such as glucose, glutamate, glutamine, ammonium, lactate, sodium, calcium, viability, and viable cell density. The proposed JITL framework introduces a paradigm shift in the way industrial Raman models are calibrated, which to the best of authors’ knowledge have not been done before.
Synthesis of β‐Chiral Amines by Dynamic Kinetic Resolution of α‐Branched Aldehydes Applying Imine Reductases
Authors: Matzel Philipp , Wenske Sebastian , Merdivan Simon , Günther Sebastian , Höhne Matthias
Published: June 2019

Imine reductases (IREDs) allow the one‐step preparation of optically active secondary and tertiary amines by reductive amination of ketones. Until now, mainly α‐chiral amines have been prepared by this route. In this study, we explored the possibility of synthesizing β‐chiral amines, a class of compounds which is also frequently found as structural motif in pharmaceuticals but much more challenging to prepare due to the following reasons: (i) The aldehyde substrate already contains the chiral center and needs to be racemized to enable full conversion. (ii) Because the intermediate imine bears the stereo center two carbon atoms remote to the imine nitrogen, it is more challenging to achieve high enantioselectivity compared to α‐chiral amine synthesis. For investigating the proof of concept, we first confirmed that different IREDs are able to convert a variety of α‐branched aldehydes when combined with five different amine substrates. The IRED from Streptomyces ipomoeae was a suitable enzyme facilitating the dynamic kinetic resolution of 2‐phenylpropanal and a substituted 2‐methyl‐3‐phenylpropanal: the corresponding N‐methylated β‐chiral amines were obtained with >95 % conversion and 78 and 95 %ee. Other amines were formed with low to moderate enantiomeric excess. This exemplifies the potential of IREDs for the one‐step synthesis of secondary β‐chiral amines, but also the challenge to identify highly selective enzymes for a desired amine product.
Electrocatalytic H2 Evolution by the Co‐Mabiq Complex Requires Tempering of the Redox‐Active Ligand
Authors: Tok G. Ceren , Freiberg Anna T. S. , Gasteiger Hubert A. , Hess Corinna R.
Published: June 2019

H2 is a promising fuel for sustainable energy conversion and storage. The development of effective earth abundant H2 evolution catalysts is integral to advancing hydrogen‐based technologies. H2 evolution by molecular complexes classically involves the formation of metal hydride intermediates. Recently, the use of redox‐active ligands has emerged as an alternate strategy for electron and proton storage. Herein, we examine the electrocatalytic behavior of [CoII(Mabiq)(THF)](PF6) (CoMbq), containing a redox‐active macrocyclic ligand, in acidic, organic media (using para‐cyanoanilinium (pCA) as the proton source). Cyclic voltammetry (CV) and Rotating Ring Disk Electrode (RRDE) voltammetry evidence a pre‐catalytic process that leads to the formation of a protonated, two‐electron reduced intermediate. This species evolves H2 at potentials negative of −1.1 VFc, as confirmed by On‐line Electrochemical Mass Spectrometry (OEMS). OEMS results further reveal a catalyst deactivation pathway. The electrochemical data denote the involvement of the redox‐active Mabiq ligand in the hydrogen evolution reaction (HER), with implications for the use of such scaffolds in electrocatalytic complexes.
KRAS Binders Hidden in Nature
Authors: Bergner Andreas , Cockcroft Xiaoling , Fischer Gerhard , Gollner Andreas , Hela Wolfgang , Kousek Roland , Mantoulidis Andreas , Martin Laetitia J. , Mayer Moriz , Müllauer Barbara , Siszler Gabriella , Wolkerstorfer Bernhard , Kessler Dirk , McConnell Darryl B.
Published: June 2019

Natural products have proven to be a rich source of molecular architectures for drugs. Here, an integrated approach to natural product screening is proposed, which uncovered eight new natural product scaffolds for KRAS—the most frequently mutated oncogenic driver in human cancers, which has remained thus far undrugged. The approach combines aspects of virtual screening, fragment‐based screening, structure‐activity relationships (SAR) by NMR, and structure‐based drug discovery to overcome the limitations in traditional natural product approaches. By using our approach, a new “snugness of fit” scoring function and the first crystal‐soaking system of the active form of KRASG12D, the protein–ligand X‐ray structures of a tricyclic indolopyrrole fungal alkaloid and an indoloisoquinolinone have been successfully elucidated. The natural product KRAS hits discovered provide fruitful ground for the optimization of highly potent natural‐product‐based inhibitors of the active form of oncogenic RAS. This integrated approach for screening natural products also holds promise for other “undruggable” targets.
Synthesis of spirostanol saponins via gold(I)‐catalyzed glycosylation in the presence of Ga(OTf)3, In(OTf)3, or HOTf
Authors: Ehianeta Teddy Stephen , Shen Dacheng , Xu Peng , Yu Biao
Published: June 2019

Summary of main observation and conclusion

An effective approach relying on a Lewis acid‐ or Brønsted acid‐assisted gold(I)‐catalyzed glycosylation has been reported in the synthesis of a panel of the representative natural spirostanol saponins, namely polyphyllin D (1), polyphyllin V (2), dioscin (3), formosanin C (4), and a derivative of polyphyllin D bearing a terminal azide group (5). This approach highlights the engagement of low loadings of Ph3AuPOTf (≤ 0.5 mol%) in the presence of Ga(OTf)3, In(OTf)3, or HOTf (~10mol%) as a co‐catalyst, at practical reaction rates as an alternative to the conventional ~10 mol% loadings of the gold(I) catalyst in the glycosylation. Polyphyllin D (1) was obtained in 41% overall yield over six steps compared to the maximum 30% yield in previous syntheses where conventional donors and promoters were used. By exploiting a regioselective rhamnosylation, a “one‐pot” approach was adopted to assemble 1 and 5, thus further strengthening the efficiency of the gold(I)‐catalyzed glycosylation.
Neuropsychological and socioeconomic outcomes in adult survivors of pediatric low‐grade glioma
Authors: Ris M. Douglas , Leisenring Wendy M. , Goodman Pamela , Di Chongzhi , Noll Jennie , Levy Wendy , Robison Leslie L. , Armstrong Gregory T.
Published: June 2019

Background

Current estimates suggest that 75% of children diagnosed with a central nervous system (CNS) tumor will become 5‐year survivors. However, survivors of childhood CNS tumors are at increased risk for long‐term morbidity.

Methods

To determine long‐term neuropsychological and socioeconomic status (SES) outcomes, adult survivors of pediatric low‐grade gliomas (n = 181) in the Childhood Cancer Survivor Study and a sibling comparison group that was frequency‐matched by age and sex (n = 105) completed a comprehensive battery of standardized neuropsychological tests and an SES assessment. Multivariable regression models compared treatment‐specific groups for neuropsychological and SES outcomes and evaluated associations with tumor location, age at diagnosis, sex, and age at evaluation.

Results

In adjusted models, survivors treated with surgery and radiotherapy (surgery+RT; median age at diagnosis, 7 years; median age at assessment, 41 years) scored lower on estimated IQ than survivors treated with surgery only, who scored lower than siblings (surgery+RT, 93.9; surgery only, 101.2; siblings, 108.5; all P values <.0001). Survivors diagnosed at younger ages had low scores for all outcomes (P < .05) except for attention/processing speed. For SES outcomes, survivors treated with surgery+RT had lower occupation scores (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.1‐5.9), lower income (OR, 2.6; 95% CI, 1.3‐5.0), and less education (OR, 2.1; 95% CI, 1.1‐4.0) than those treated with surgery only.

Conclusions

Decades after treatment, survivors treated with radiotherapy and at younger ages had poorer neuropsychological and SES outcomes. Lifelong surveillance of survivors of pediatric low‐grade gliomas may be warranted as life events, stages, and transitions (employment, family, and aging) present new challenges and risks.
DFT Study of Methanol Adsorption on Defect‐Free CeO2 Low‐Index Surfaces
Authors: Liu Zhao , Sorrell Charles C. , Koshy Pramod , Hart Judy N.
Published: June 2019

Methanol decomposition is a promising method for hydrogen production. However, the performance of current catalysts for this process is not sufficient for commercial applications. In this work, methanol adsorption on the CeO2 low‐index surfaces is studied by density functional theory (DFT). The results show that methanol always dissociates spontaneously on the (100) surface, whereas dissociation on the (110) surface is site‐selective; dissociation does not occur at all on the (111) surface, where only weak physisorption is found. The results confirm that surfaces with higher energies are more catalytically active. Analysis of the surface geometries shows that the dominant factors for the dissociation of methanol are the degree of undercoordination and the charges of the surface ions. The adsorption energy of each methanol molecule decreases with increasing coverage and there is a transition threshold between dissociative and associative adsorption. The present work indicates that a strategy to design catalysts with high activity is to maximize exposure of surfaces on which the ions have a high degree of undercoordination and a strong tendency to donate/accept electrons. The results demonstrate the importance of appropriately selecting and controlling exposed facets and particle morphology for optimizing catalyst performance.
Odd‐Even Effect on Luminescence Properties of Europium Aliphatic Dicarboxylate Complexes
Authors: Assunção Israel P. , Carneiro Neto Albano N. , Moura Renaldo T. , Pedroso Cássio C. S. , Silva Ivan G. N. , Felinto Maria C. F. C. , Teotonio Ercules E. S. , Malta Oscar L. , Brito Hermi F.
Published: June 2019

The odd–even effect in luminescent [Eu2(L)3(H2O)x]⋅y(H2O) complexes with aliphatic dicarboxylate ligands (L: OXA, MAL, SUC, GLU, ADP, PIM, SUB, AZL, SEB, UND, and DOD, where x=2–6 and y=0–4), prepared by the precipitation method, was observed for the first time in lanthanide compounds. The final dehydration temperatures of the Eu3+ complexes show a zigzag pattern as a function of the carbon chain length of the dicarboxylate ligands, leading to the so‐called odd‐even effect. The FTIR data confirm the ligand–metal coordination via the mixed mode of bridge–chelate coordination, except for the Eu3+‐oxalate complex. XRD results indicate that the highly crystalline materials belong to the monoclinic system. The odd–even effect on the 4 f–4 f luminescence intensity parameters (Ω2 and Ω4) is explained by using an extension of the dynamic coupling mechanism, herein named the ghost‐atom model. In this method, the long‐range polarizabilities (
) were simulated by a ghost atom located at the middle of each ligand chain. The values of
were estimated using the localized molecular orbital approach. The emission intrinsic quantum yield (
) of the Eu3+ complexes also presented an the odd‐even effect, successfully explained in terms of the zigzag behavior shown by the Ω2 and Ω4 intensity parameters. Luminescence quenching due to water molecules in the first coordination sphere is also discussed and rationalized.
Lead‐Free Perovskites: Metals Substitution towards Environmentally Benign Solar Cell Fabrication
Authors: Shalan Ahmed Esmail , Kazim Samrana , Ahmad Shahzada
Published: June 2019

Perovskite solar cells have attracted significant attention during the current decade owing to their efficacy and photovoltaics performance, which has reached a new milestone in the thin‐film category. Perovskite solar cells have witnessed a remarkable 25.2 % light‐to‐electricity conversion efficiency; however, the toxicity of the commonly employed Pb counterpart towards humans as well as the environment, in addition to material instability, are current bottlenecks towards commercial application. The scientific community has explored other metal ions as substitutions for Pb, while preserving the unique properties of the material, to produce environment‐friendly perovskites. In this Review, we highlight the recent developments and challenges of Pb‐free halide perovskite‐based light harvesters for solar cell applications. This summary is intended to aid in the further development of a materials library for this sustainable technology.
Applications of Flow Cytometric Immunophenotyping in the Diagnosis and Posttreatment Monitoring of B and T Lymphoblastic Leukemia/Lymphoma
Authors: DiGiuseppe Joseph A. , Wood Brent L.
Published: June 2019

In this review, we discuss applications of flow cytometric immunophenotyping (FCI) in the diagnostic evaluation and posttreatment monitoring of B and T lymphoblastic leukemia/lymphoma. We describe practical approaches to FCI at the time of diagnosis, with an emphasis on blast identification, lineage assignment, and distinction of B and T lymphoblastic leukemia/lymphoma from their morphologic and immunophenotypic mimics. We further review flow cytometric assays for the detection of minimal or measurable residual disease (MRD) after treatment, and illustrate both standard approaches, and newer strategies for improving sensitivity and circumventing the loss of immunophenotypic targets after immunotherapy. © 2019 International Clinical Cytometry Society
Web video classification with visual and contextual semantics
Authors: Afzal Mehtab , Shah Nadir , Muhammad Tufail
Published: June 2019

On the social Web, the amount of video content either originated from wireless devices or previously received from media servers has increased enormously in the recent years. The astounding growth of Web videos has stimulated researchers to propose new strategies to organize them into their respective categories. Because of complex ontology and large variation in content and quality of Web videos, it is difficult to get sufficient, precisely labeled training data, which causes hindrance in automatic video classification. In this paper, we propose a novel content‐ and context‐based Web video classification framework by rendering external support through category discriminative terms (CDTs) and semantic relatedness measure (SRM). Mainly, a three‐step framework is proposed. Firstly, content‐based video classification is proposed, where twofold use of high‐level concept detectors is leveraged to classify Web videos. Initially, category classifiers induced from VIREO‐374 detectors are trained to classify Web videos, and then concept detectors with high confidence for each video are mapped to CDT through SRM‐assisted semantic content fusion function to further boost the category classifiers, which intuitively provide a more robust measure for Web video classification. Secondly, a context‐based video classification is proposed, where twofold use of contextual information is also harnessed. Initially, cosine similarity and then semantic similarity are measured between text features of each video and CDT through vector space model (VSM)‐ and SRM‐assisted semantic context fusion function, respectively. Finally, classification results from content and context are fused to compensate for the shortcomings of each other, which enhance the video classification performance. Experiments on large‐scale video dataset validate the effectiveness of the proposed solution.
Taking insight into the gut microbiota of three spider species: No characteristic symbiont was found corresponding to the special feeding style of spiders
Authors: Hu Guowen , Zhang Lihua , Yun Yueli , Peng Yu
Published: June 2019

Microorganisms in insect guts have been recognized as having a great impact on their hosts' nutrition, health, and behavior. Spiders are important natural enemies of pests, and the composition of the gut microbiota of spiders remains unclear. Will the bacterial taxa in spiders be same as the bacterial taxa in insects, and what are the potential functions of the gut bacteria in spiders? To gain insight into the composition of the gut bacteria in spiders and their potential function, we collected three spider species, Pardosa laura, Pardosa astrigera, and Nurscia albofasciata, in the field, and high‐throughput sequencing of the 16S rRNA V3 and V4 regions was used to investigate the diversity of gut microbiota across the three spider species. A total of 23 phyla and 150 families were identified in these three spider species. The dominant bacterial phylum across all samples was Proteobacteria. Burkholderia, Ralstonia, Ochrobactrum, Providencia, Acinetobacter, Proteus, and Rhodoplanes were the dominant genera in the guts of the three spider species. The relative abundances of Wolbachia and Rickettsiella detected in N. albofasciata were significantly higher than those in the other two spider species. The relative abundance of Thermus, Amycolatopsis, Lactococcus, Acinetobacter Microbacterium, and Koribacter detected in spider gut was different among the three spider species. Biomolecular interaction networks indicated that the microbiota in the guts had complex interactions. The results of this study also suggested that at the genus level, some of the gut bacteria taxa in the three spider species were the same as the bacteria in insect guts.
Homoploid hybridization of plants in the Hengduan mountains region
Authors: Yang Rui , Folk Ryan , Zhang Ningning , Gong Xun
Published: June 2019

The Hengduan Mountains Region (HMR) is a major global biodiversity hotspot. Complex tectonic and historical climatic conditions created opportunities for natural interspecific hybridization. Likewise, anthropogenic disturbance potentially raises the frequency of hybridization. Among species studies to date, the frequency of homoploid hybridization appears in the HMR. Of nine taxa in which natural hybridization has been detected, three groups are involved in homoploid hybrid speciation, and species pairs from the remaining six genera suggest that continuous gene flow occurs in hybrid zones. Reproductive isolation may greatly affect the dynamic and architecture of hybrid zones in the HMR. Asymmetrical hybridization and introgression can primarily be attributed to both prezygotic and postzygotic barriers. The frequent observation of such asymmetry may imply that reproductive barrier contributes to maintaining species boundaries in the alpine region. Ecological isolations with environmental disturbance may promote breeding barriers between parental species and hybrids. Hybrid zones may be an important phase for homoploid hybrid speciation. Hybrid zones potentially provided abundant genetic resources for the diversification of the HMR flora. The ecological and molecular mechanisms of control and mediation for natural hybridization will help biologists to understand the formation of biodiversity in the HMR. More researches from ecological and molecular aspects were required in future studies.