bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure‐Based Design of a Macrocyclic PROTAC
Authors: Testa Andrea , Hughes Scott J. , Lucas Xavier , Wright Jane E. , Ciulli Alessio 
Published: November 2019

AbstractConstraining a molecule in its bioactive conformation via macrocyclization represents an attractive strategy to rationally design functional chemical probes. While this approach has been applied to enzyme inhibitors or receptor antagonists, to date it remains unprecedented for bifunctional molecules that bring proteins together, such as PROTAC degraders. Herein, we report the design and synthesis of a macrocyclic PROTAC by adding a cyclizing linker to the BET degrader MZ1. A co‐crystal structure of macroPROTAC‐1 bound in a ternary complex with VHL and the second bromodomain of Brd4 validated the rational design. Biophysical studies revealed enhanced discrimination between the second and the first bromodomains of BET proteins. Despite a 12‐fold loss of binary binding affinity for Brd4, macroPROTAC‐1 exhibited cellular activity comparable to MZ1. Our findings support macrocyclization as an advantageous strategy to enhance PROTAC degradation potency and selectivity between homologous targets.
Performance comparison of feedforward neural network training algorithms in modelling microwave pyrolysis of oil palm fibre for hydrogen and biochar production
Authors: Nasrudin Nor Anisa , Jewaratnam Jegalakshimi , Hossain Md Arafat , Ganeson Poo Balan 
Published: November 2019

AbstractMicrowave pyrolysis of oil palm fibre (OPF) was conducted to study the effect of microwave power, temperature, and nitrogen (N2) flow rate on the production of hydrogen and biochar. The effect of microwave power ranging from 400 to 900 W, reaction temperatures ranging from 450°C to 700°C, and N2 flow rates ranging 200 to 1,200 cm3 min−1 were investigated. The microwave power, reaction temperature, and N2 flow rates are directly proportional to hydrogen and inversely proportional to biochar yield. The characteristics of the biochar were analysed using CHNOS, scanning electron microscopy, and Brunauer–Emmett–Teller results. Central composite design was used to optimize the number of experiment. The optimized experimental datasets were used as inputs for developing a model that can predict the weight of hydrogen and biochar from microwave pyrolysis of OPF. A multilayer feedforward neural network model was developed by comparing the performance of 11 different types of backpropagation training algorithms. The 11 training algorithms belong to six classes, which are (a) additive momentum, (b) self‐adaptive learning rate, (c) resilient backpropagation, (d) conjugate gradient, (e) quasi‐Newton, and (f) Bayesian regulation (BR). Best performing training algorithm was selected based on the lowest error values computed. The objective of this research is to identify the most suitable training algorithm for this process. Levenberg–Marquardt and BR exhibited very good performance. BR exhibited best performance with lowest error values in predicting weight of hydrogen and biochar. The testing data error values for hydrogen weight is 0.216 root mean square error (RMSE), 0.144 mean absolute error (MAE), and 0.020 mean absolute percentage error (MAPE), and biochar is 0.886 RMSE, 0.489 MAE, and 0.019 MAPE. The optimum number of hidden neuron for this algorithm is 19 with mean square error 0.23. The biochar exhibits porous structure suggesting possible land application.
Study on the formation process of low‐temperature ash deposition induced by ammonium bisulfate in pulverized coal‐fired boiler
Authors: Wang Limin , Bu Yufan , Tang Chunli , Lv Cheng , Chen Xun , Che Defu 
Published: November 2019

AbstractIn order to explore the mechanism of low‐temperature ash deposition induced by ammonium bisulfate (ABS), ash deposits, and a corroded heat transfer plate in the rotary air preheater (RAPH) of a 1,000‐MW pulverized coal‐fired power plant in China were analyzed by X‐ray fluorescence, ion chromatography, X‐ray diffraction, and scanning electron microscope equipped with energy dispersive X‐ray spectroscopy. The element composition, main compounds, and ammonium ion in the samples were analyzed. The thermal gravimetric analysis of ash samples was conducted to infer the type of ammonium salt ultimately existing in the ash. The prediction of the ABS deposition range coincides well with both the area of serious ash deposition and the area of NH4+ distribution obtained by ion chromatography. The cause for corrosion and plugging in the RAPH was proposed by analyzing the reactions or mineral transformations involved in the ash deposits. The results indicate that ABS can form in a large height range in the RAPH. The ammonium induces the sulfur trioxide to deposit on and react with the metal plate or the ash particles to form sulfates, which act as the bridging agent, finally leading to serious plugging problems in the RAPH.
Lanthanide‐Based Luminescent Materials for Waveguide and Lasing
Authors: Chen Xian , Sun Tianying , Wang Feng 
Published: November 2019

AbstractMicrolasers and waveguides have wide applications in the fields of photonics and optoelectronics. Lanthanide‐doped luminescent materials featuring large Stokes/anti‐Stokes shift, long excited‐state lifetime as well as sharp emission bandwidth are excellent optical components for photonic applications. In the past few years, great progress has been made in the design and fabrication of lanthanide‐based waveguides and lasers at the micrometer length scale. Waveguide structures and microcavities can be fabricated from lanthanide‐doped amorphous materials through top‐down process. Alternatively, lanthanide‐doped organic compounds featuring large absorption cross‐section can self‐assemble into low‐dimensional structures of well‐defined size and morphology. In recent years, lanthanide‐doped crystalline structures displaying highly tunable excitation and emission properties have emerged as promising waveguide and lasing materials, which substantially extends the range of lasing wavelength. In this minireview, we discuss recent advances in lanthanide‐based luminescent materials that are designed for waveguide and lasing applications. We also attempt to highlight challenging problems of these materials that obstacle further development of this field.
State‐feedback stabilization and inverse optimal control for stochastic high‐order nonlinear systems with time‐varying powers
Authors: Li Wuquan , Liu Ying , Yao Xiaoxiao 
Published: November 2019

AbstractThis paper considers the stability and optimality problems associated with stochastic high‐order nonlinear systems with time‐varying powers. This research extends previous studies on the plant with constant powers. In this paper, we firstly construct a state‐feedback controller to ensure that the equilibrium at the origin of the closed‐loop system is globally asymptotically stable (GAS) in probability. Then we redesign a new optimal controller with infinite gain margin to solve the inverse optimal stabilization (IOS) problem. Specifically, the optimal controller is not only optimal with respect to a meaningful cost functional but also globally asymptotically stabilizes the closed‐loop system. The efficiency of the designed controllers is demonstrated by a simulation example.
Sulfolane‐Based Ethylene Carbonate‐Free Electrolytes for LiNi0.6Mn0.2Co0.2O2−Li4Ti5O12 Batteries
Authors: Björklund Erik , Göttlinger Mara , Edström Kristina , Younesi Reza , Brandell Daniel 
Published: November 2019

AbstractMost electrolytes in today's lithium‐ion batteries contain a large proportion of ethylene carbonate (EC) mixed with other alkyl carbonate‐based solvents. EC has, however, been shown to be unstable at the high potentials at which several novel cathode materials are electrochemically active. Here, different mixtures of sulfolane and DMC are investigated in this context. The electrochemical stability is explored in addition to galvanostatic cycling of LiNi0.6Mn0.2Co0.2O2‐Li4Ti5O12 (NMC‐LTO) cells. The measurement of the ionic conductivity showed that mixing 25 % sulfolane into DMC improved the electrolyte properties as compared to pure DMC, making the conductivity similar to EC:DEC electrolytes and therefore fully functional. Moreover, the addition of sulfolane slightly enhanced the capacity retention, likely caused by formation of thinner and more stable surface layers on the LTO electrodes as determined by X‐ray photoelectron spectroscopy (XPS). The cycling performance is especially improved for sulfolane‐based electrolytes during cycling at sub‐zero temperatures.
Cellular Adaptation Relies on Regulatory Proteins Having Episodic Memory
Authors: Stan Razvan C. , Bhatt Darshak K. , de Camargo Maristela M. 
Published: November 2019

AbstractThe ability to memorize changes in the environment is present at all biological levels, from social groups and individuals, down to single cells. Trans‐generational memory is embedded subcellularly through genetic and epigenetic mechanisms. Evidence that cells process and remember features of the immediate environment using protein sensors is reviewed. It is argued that this mnemonic ability is encapsulated within the protein conformational space and lasts throughout its lifetime, which can overlap with the lifespan of the organism. Means to determine diachronic changes in protein activity are presented.
Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv
Authors: Henriksson M. , Björnsson B. , Sternby Eilard M. , Lindell G. , Strömberg C. , Hemmingsson O. , Isaksson B. , Rizell M. , Sandström P. 
Published: November 2019

Abstract

Background
Consistent data on clinical features, treatment modalities and long-term survival in patients with hepatocellular carcinoma (HCC) using nationwide quality registers are lacking. This study aimed to describe treatment patterns and survival outcomes in patients diagnosed with HCC using a national maintained database.

Methods
Characteristics and treatment patterns in patients diagnosed with HCC and registered in the national register of liver and bile duct tumours (SweLiv) between 2009 and 2016 were reviewed. Overall survival (OS) was estimated using Kaplan–Meier analysis and the log rank test to compare subgroups for clinical features, treatment modalities and outcomes according to the year of treatment.

Results
A total of 3376 patients with HCC were registered over 8 years, 246 (7·3 per cent) of whom underwent transplantation. Some 501 (14·8 per cent) and 390 patients (11·6 per cent) had resection and ablation as primary treatment. Transarterial chemoembolization and systemic sorafenib treatment were intended in 476 (14·1 per cent) and 426 patients (12·6 per cent) respectively; the remaining 1337 (39·6 per cent) were registered but referred for best supportive care (BSC). The 5-year survival rate was approximately 75 per cent in the transplantation group. Median OS was 4·6 (i.q.r. 2·0 to not reached) years after resection and 3·1 (2·3–6·7) years following ablation. In patients referred for palliative treatment, median survival was 1·4 (0·8–2·9), 0·5 (0·3–1·2) and 0·3 (0·1–1·0) years for the TACE, sorafenib and BSC groups respectively (P &lt; 0·001). Median survival was 0·9 years for the total HCC cohort in 2009–2012, before publication of the Swedish national treatment programme, increasing to 1·4 years in 2013–2016 (P &lt; 0·001).

Conclusion
The survival outcomes reported were in line with previous results from smaller cohorts. The introduction of national guidelines may have contributed to improved survival among patients with HCC in Sweden.
Computational simulation and experimental validation of an engineering problem: A case study on heat transfer in cylindrical fin with phase‐change material
Authors: R. Prithvi Raj , M. P. Midhun , D. Prakash 
Published: November 2019

AbstractIn this study, an extensive numerical simulation on the fins with a phase‐change material (PCM) has been conducted under various design aspects to understand the heat transfer mechanism through a project‐based learning system. A detailed methodology on the use of computational fluid dynamics (CFD) tools for an engineering problem is discussed along with experimental validation. Initially, a required experimental test setup has been developed, and a cylindrical fin with PCM is fabricated and tested for heat transfer. Cylindrical fin is made from aluminum material, and paraffin is used as PCM since its application is widely spread in energy industries. Later, CFD simulation is performed on the cylindrical fin in ANSYS Workbench by including both heat transfer and phase‐change phenomenon of PCM. The CFD solver solves the partial differential equation through the finite volume method and the results obtained from the CFD simulation are checked for grid independence. Also, the obtained results are compared with experimental results for validation and found a good agreement. After validation, the influence of the PCM zone aspect ratio, PCM zone location, and groove over fin on heat transfer are numerically studied. From the obtained results, it is noticed that increasing the PCM volume increases the melting time and also lowers the fin tip temperature. Finally, fins with peripheral grooves and PCM proves as a good combination for a better heat transfer rate. This kind of simulation studies helps the students to understand the complex heat transfer mechanism through project‐based learning and also expertise the students.
CD44‐associated radioresistance of glioblastoma in irradiated brain areas with optimal tumor coverage
Authors: Liu Wei‐Hsiu , Lin Jang‐Chun , Chou Yu‐Ching , Li Ming‐Hsien , Tsai Jo‐Ting 
Published: November 2019

AbstractGlioblastoma multiforme (GBM) requires radiotherapy (RT) as its definitive management. However, GBM still has a high local recurrence rate even after RT. Cancer stem‐like cells (CSCs) might enable GBM to evade irradiation damage and cause therapeutic failure. The optimal RT plan should achieve a planning target volume (PTV) coverage of more than 95% but cannot always meet the requirements. Here, we demonstrate that irradiation with different tumor coverage rates to different brain areas has similar effects on GBM. To retrospectively analyze the relationship between PTV coverage and the survival rate in 26 malignant glioblastoma patients, we established primary cell lines from patient‐derived malignant glioblastoma cells with the PTV95 (PTV coverage of more than 95%) program (GBM‐MG1 cells) and the Non‐PTV95 (poor PTV coverage of less than 95%) program (GBM‐MG2 cells). The clinical results of PTV95 and Non‐PTV95 showed no difference in the overall survival (OS) rate (P = .390) between the two different levels of PTV coverage. GBM‐MG1 (PTV95 program) cells exhibited higher radioresistance than GBM‐MG2 (Non‐PTV95 program) cells. CD44 promotes radioresistance, CSC properties, angiogenesis and cell proliferation in GBM‐MG1 (PTV95 program) cells. GBM patients receiving RT with the PTV95 program exhibited higher radioresistance, CSC properties, angiogenesis and cell proliferation than GBM patients receiving RT with the Non‐PTV95 program. Moreover, CD44 plays a crucial role in these properties of GBM patients with the PTV95 program.
A V‐Nitrogenase Variant Containing a Citrate‐Substituted Cofactor
Authors: Newcomb Megan P. , Lee Chi Chung , Tanifuji Kazuki , Jasniewski Andrew J. , Liedtke Jasper , Ribbe Markus W. , Hu Yilin 
Published: November 2019

AbstractNitrogenases catalyze the ambient reduction of N2 and CO at its cofactor site. Herein we present a biochemical and spectroscopic characterization of an Azotobacter vinelandii V nitrogenase variant expressing a citrate‐substituted cofactor. Designated VnfDGKCit, the catalytic component of this V nitrogenase variant has an αβ2(δ) subunit composition and carries an 8Fe P* cluster and a citrate‐substituted V cluster analogue in the αβ dimer, as well as a 4Fe cluster in the “orphaned” β‐subunit. Interestingly, when normalized based on the amount of cofactor, VnfDGKCit shows a shift of N2 reduction from H2 evolution toward NH3 formation and an opposite shift of CO reduction from hydrocarbon formation toward H2 evolution. These observations point to a role of the organic ligand in proton delivery during catalysis and imply the use of different reaction sites/mechanisms by nitrogenase for different substrate reductions. Moreover, the increased NH3/H2 ratio upon citrate substitution suggests the possibility to modify the organic ligand for improved ammonia synthesis in the future.
A case of giant cell arteritis simultaneously diagnosed with chronic subdural hematoma
Authors: Otani Yuichiro , Kanno Keishi , Kikuchi Yuka , Kametani Takahiro , Kobayashi Tomoki , Tazuma Susumu 
Published: November 2019

AbstractHere, we describe a case of giant cell arteritis (GCA) simultaneously diagnosed with chronic subdural hematoma. In this case, head to chest computed tomography angiography was useful for the diagnosis and treatment of GCA.
Two‐Dimensional Metal–Organic Framework Nanosheets with Cobalt‐Porphyrins for High‐Performance CO2 Electroreduction
Authors: Zhang Xiang‐Da , Hou Shu‐Zhen , Wu Jian‐Xiang , Gu Zhi‐Yuan 
Published: November 2019

AbstractThe electrochemical reduction of CO2 presents a promising strategy to mitigate the greenhouse effect and reduce excess carbon dioxide emission to realize a carbon‐neutral energy cycle, but it suffers from the lack of high‐performance electrocatalysts. In this work, catalytic active cobalt porphyrin [TCPP(Co)=(5,10,15,20)‐tetrakis(4‐carboxyphenyl)porphyrin‐CoII] was precisely anchored onto water‐stable 2D metal–organic framework (MOF) nanosheets (Zr‐BTB) to obtain ultrathin 2D MOF nanosheets [TCPP(Co)/Zr‐BTB] with accessible catalytic sites for the CO2 reduction reaction. Compared with molecular cobalt porphyrin, the TCPP(Co)/Zr‐BTB exhibits an ultrahigh turnover frequency (TOF=4768 h−1 at −0.919 V vs. reversible hydrogen electrode, RHE) owing to high active‐site utilization. In addition, three post‐modified 2D MOF nanosheets [TCPP(Co)/Zr‐BTB‐PABA, TCPP(Co)/Zr‐BTB‐PSBA, TCPP(Co)/Zr‐BTB‐PSABA] were obtained, with the modifiers of p‐(aminomethyl)benzoic acid (PABA), p‐sulfobenzoic acid potassium (PSBA), and p‐sulfamidobenzoic acid (PSABA), to change the micro‐environments around TCPP(Co) through the tuning of steric effects. Among them, the TCPP(Co)/Zr‐BTB‐PSABA exhibited the best performance with a faradaic efficiency (FECO) of 85.1 %, TOF of 5315 h−1, and jtotal of 6 mA cm−2 at −0.769 V (vs. RHE). In addition, the long‐term durability of the electrocatalysts is evaluated and the role of pH buffer is revealed.
A Mild and Versatile Friedel–Crafts Methodology for the Diversity‐Oriented Synthesis of Redox‐Active 3‐Benzoylmenadiones with Tunable Redox Potentials
Authors: Cotos Leandro , Donzel Maxime , Elhabiri Mourad , Davioud‐Charvet Elisabeth 
Published: November 2019

AbstractA series of highly diversified 3‐aroylmenadiones was prepared by a new Friedel–Crafts acylation variant/oxidative demethylation strategy. A mild and versatile acylation was performed between 1,4‐dimethoxy‐2‐methylnaphthalene and various activated/deactivated benzoic and heteroaromatic carboxylic acids, in the presence of mixed trifluoroacetic anhydride and triflic acid, at room temperature and in air. The 1,4‐dimethoxy‐2‐methylnaphthalene‐derived benzophenones were isolated in high yield, and submitted to oxidative demethylation with cerium ammonium nitrate to produce 3‐benzoylmenadiones. All 1,4‐naphthoquinone derivatives were investigated as redox‐active electrophores by cyclic voltammetry. The electrochemical data recorded for 3‐acylated menadiones are characterized by a second redox process, the potentials of which cover a wide range of values (500 mV). These data emphasize the ability of the generated structural diversity at the 3‐aroyl chain of these electrophores to fine‐tune their corresponding redox potentials. These properties are of significance in the context of antimalarial drug development and understanding of the mechanism of bioactivation/action.
Designing Molecular Spanners to Throw in the Protein Networks
Authors: Serapian Stefano A. , Colombo Giorgio 
Published: November 2019

AbstractProteins govern most aspects of cellular life and, through specific interfaces, are typically involved in intricate protein–protein interaction (PPI) networks and signaling pathways. Subtle up‐ or downregulation of key protein functions and PPIs results in disease; still, the preferred option to contrast the role of a protein in disease and healthy conditions alike remains its outright shutdown through orthosteric ligands that block its active site. Here, we explore subtler alternatives to modulate proteins and PPIs. Driven by a view of proteins as dynamic entities, we discuss ways to identify allosteric binding sites, which, when targeted by tailored ligands, can induce significant changes in the active site of a protein, and lead to agonistic or antagonistic effects. We also summarize the selective regulation of specific PPIs—either direct or allosteric—and show that effects can be stabilizing as well as destabilizing, depending on how the conformational equilibrium of a protein is shifted.
Spiro‐Carbon: A Metallic Carbon Allotrope Predicted from First Principles Calculations
Authors: Oliveira Felipe L. , Capaz Rodrigo B. , Esteves Pierre M. 
Published: November 2019

AbstractA structurally stable microporous metallic carbon allotrope, poly(spiro[2.2]penta‐1,4‐diyne) or, for short, spiro‐carbon, withI41/amd(D4h) symmetry is predicted by first‐principles calculations using density functional theory (DFT). The calculations of electronic, vibrational, and structural properties show that spiro‐carbon has lower relative energy than other elusive carbon allotropes such as T‐Carbon and 1‐diamondyne (Y‐Carbon). Its structure can be pictured as a set oftrans‐cisoid‐polyacetylene chains tangled and interconnected together bysp3carbon atoms. Calculations reveal a metallic electronic structure arising from an “intrinsic doping” oftrans‐cisoid‐polyacetylene chains withsp3carbon atoms. Possible synthetic routes and various simulated spectra (XRD, NMR, and IR absorption) are provided in order to guide future efforts to synthesize this novel material.
Preparation of Lipid Nanodiscs with Lipid Mixtures
Authors: Li Mavis Jiarong , Atkins William M. , McClary Wynton D. 
Published: November 2019

AbstractLipid nanodiscs provide a native‐like lipid environment for membrane proteins, and they have become a valuable platform for the study of membrane biophysics. A range of biophysical and biochemical analyses are enabled when membrane proteins are captured in lipid nanodiscs. Two parameters that can be controlled when capturing membrane proteins in lipid nanodiscs are the radius, and hence the surface area of the lipid surface, and the composition of the lipid bilayer. Despite their emergence as a versatile tool, most studies with lipid nanodiscs in the literature have focused on nanodiscs of a single radius with a single lipid. In light of the complexity of biological membranes, it is likely that nanodiscs with multiple membrane components would be more sophisticated models for membrane research. It is possible to prepare nanodiscs with more complex lipid mixtures to probe the effects of lipid composition on several aspects of membrane biochemistry. Detailed protocols are described here for the preparation of nanodiscs with mixtures of phospholipids, incorporation of cholesterol, and incorporation of a spectroscopic lipid probe. These protocols provide starting points for the construction of nanodiscs with more physiological membrane compositions or with useful biophysical probes. © 2019 by John Wiley & Sons, Inc.Basic Protocol 1: Assembly of mixed lipid nanodiscsBasic Protocol 2: Assembly of nanodiscs with cholesterolBasic Protocol 3: Incorporation of laurdan into nanodiscs for membrane fluidity measurements