bluuebunny/crossref_metadata_2025_split huggingface dataset:
Puckering the Planar Landscape of Fragments: Design and Synthesis of a 3D Cyclobutane Fragment Library
Authors: Hamilton David J. , Beemsterboer Marieke , Carter Caroline M. , Elsayed Jasmina , Huiberts Rilana E. M. , Klein Hanna F. , O'Brien Peter , de Esch Iwan J. P. , Wijtmans Maikel 
Published: March 2022

AbstractFragment‐based drug discovery (FBDD) has a growing need for unique screening libraries. The cyclobutane moiety was identified as an underrepresented yet attractive three‐dimensional (3D) scaffold. Synthetic strategies were developed via a key 3‐azido‐cyclobutanone intermediate, giving potential access to a range of functional groups with accessible growth vectors. A focused set of 33 novel 3D cyclobutane fragments was synthesised, comprising three functionalities: secondary amines, amides, and sulfonamides. This library was designed using Principal Component Analysis (PCA) and an expanded version of the rule of three (RO3), followed by Principal Moment of Inertia (PMI) analysis to achieve both chemical diversity and high 3D character. Cis and trans ring isomers of library members were generated to maximise the shape diversity obtained, while limiting molecular complexity through avoiding enantiomers. Property analyses of the cyclobutane library indicated that it fares favourably against existing synthetic 3D fragment libraries in terms of shape and physicochemical properties.
An ensemble method for feature selection and an integrated approach for mitigation of distributed denial of service attacks
Authors: Chanu Usham Sanjota , Singh Khundrakpam Johnson , Chanu Yambem Jina 
Published: March 2022

AbstractDistributed denial of service attacks (DDoS) penetrate numerous computer system and implant malicious codes thereby making them ready for launching a collaborative attack. These attacks paralyze the target system mainly the web server by exhausting their network resources of the target server. The threats posed by DDoS attacks on the Internet demands for effective detection and mitigation methods of these attacks. In the paper, we proposed an integrated method for detection and mitigation of DDoS attack using machine learning and a line of defenses respectively. The detection phase consists of feature selection through ensemble feature selection algorithm and classification using machine learning algorithm. Feature selection algorithms are important as they reduce the dimension of the dataset. The selection of an efficient classification model will improve the detection rate of the proposed system. In the mitigation phase, we introduce two lines of defense to minimize the exhaustion of the victim server's resources. Using the existing dataset, we show experimentally that it is possible to detect the presence of attacks and mitigate them to a minimum level. The proposed integrated method yields an accuracy of 97.8% in detecting the attacks and able to reduce the utilization of processors upto an average of 25.95%.
Evaluating macro‐ and micro‐mineral contents and agronomic traits of Turkish oat landraces
Authors: Kilinç Fatih Mehmet , Sakiroglu Muhammet , Yilmaz Cafer Hakan , Akkaya Aydın , Dokuyucu Tevrican , Gezginç Hasan , Yüce İlker , Dumlupinar Ziya 
Published: March 2022

AbstractThe cultivated oat (Avena sativa L. and A. byzantina Coch.) is an important annual cereal and forage plant. A large collection of historical oat landraces gathered from different diversity centers is maintained in various seed banks. A historical oat collection consisted of 174 Turkish landraces were evaluated for agronomic performance and mineral nutrient content. The experiment was arranged in an augmented design with six replications of 10 check cultivars and 29 landraces in each block. The most important finding of the study was that the landraces manifested a wide range of variation in all agronomic traits and that some historical landraces outperformed the check cultivars. Since it was dry for the grain‐filling period (GFP) in 2019, some drought‐tolerant landraces were identified. In addition, the top 10 landraces for yield and mineral content were also identified based on each year's performance as well as on the 3‐yr average. The landrace TL69/PI411401 was found to be prominent for high calcium (Ca), magnesium (Mg), phosphorus (P), boron (B), and zinc (Zn) content; TL86/PI167378 for Ca, P, potassium (K), and iron (Fe) contents; and TL71/PI411414 for Ca, P, B, and Zn content.
Mechanism of Preferential Hydrogenation of Hydroxymethyl Group to Aldehyde Group in 5‐Hydroxymethylfurfural over W2C‐Based Catalyst
Authors: Tai Wei , Fu Shuai , Liu Ting‐Hao , Yang Hua‐Qing , Hu Chang‐Wei 
Published: March 2022

AbstractA W4C2 cluster was used to model a W2C catalyst with the armchair model of activated carbon support, noted as W4C2/AC. Over W4C2/AC, the mechanism for the hydrogenation of both −H2OH and −CHO groups in 5‐hydroxymethylfurfural (HMF) was theoretically studied in tetrahydrofuran at GGA‐PBE/DNP level. 5‐Methylfurfural was the major product from only hydrodehydration of the −CH2OH group, whereas 2,5‐dihydroxymethylfuran was the minor product from the hydrogenation of both −CH2OH and −CHO groups. The rate‐determining steps were concerned with the −C(H)2−H bond formation for the hydrodehydration of −CH2OH group, and the −(OH)(H)−H bond formation for the hydrogenation of −CHO group. Kinetically, W‐sites promoted the hydrodehydration of −CH2OH group and inhibited the hydrogenation of −CHO group. This stemmed from the strong Lewis acidity of W‐sites, which easily accepted the lone‐pair electrons of the oxygen atom in the −C(OH)(H)− group, making −C(OH)(H)−H bond formation hard, and hampering the hydrogenation of the −CHO group.
Sustainable Catalytic Transformation of Biomass‐Derived 5‐Hydroxymethylfurfural to 2,5‐Bis(hydroxymethyl)tetrahydrofuran
Authors: Chien Truong Cong , Kumar Mishra Dinesh , Hyeok Ko Sang , Jin Kim Yong , Suh Young‐Woong 
Published: March 2022

Abstract5‐Hydroxymethylfurfural (5‐HMF), one of the most important platform molecules in biorefinery, can be directly obtained from a vast diversity of biomass materials. Owing to the reactive functional groups (−CHO and −CH2OH) in the structure, this versatile building block undertakes several transformations to provide a wealth of high value‐added products. Among numerous well‐established paradigms, the catalytic hydrogenation of 5‐HMF towards 2,5‐bis(hydroxymethyl)tetrahydrofuran (BHMTHF) is of great interest because this downstream diol can be exploited in a wide range of industrial applications. Not surprisingly, incessant endeavors from both academia and industry to upgrade this catalytic process have been established over the years. The main aim of this Review was to provide a comprehensive overview on the development of heterogeneous metal catalysts for the 5‐HMF‐to‐BHMTHF transformation. Herein, the rational design and utility of hydrogenating catalysts were elaborated in many aspects including metal types (Ni, Co, Pd, Ru, Pt, and bimetals), solid supports, preparation method, recyclability, operating conditions, and reaction regime (batch and continuous flow). In addition, the assessment of cooperative catalysts to convert carbohydrates into BHMTHF under one‐pot cascade, tentative mechanism, as well as prospects and challenges for the chemo‐selective hydrogenation of 5‐HMF were also highlighted.
Hierarchical Pores‐Confined Ultrasmall Cu Nanoparticles for Efficient Oxidation of 5‐Hydroxymethylfurfural
Authors: Lu Qingwen , Zhao Xin , Fang Ruiqi , Li Yingwei 
Published: March 2022

AbstractPyrolysis is one of the most widely utilized protocols for the preparation of nanoconfined metal species for heterogeneous catalysis, but it still suffers from the uncontrollable composition evolution process with undesired metal sintering and porous structure collapse. Herein, a novel and versatile molten salt‐assisted pyrolysis strategy was demonstrated for the preparation of ultrasmall transition‐metal nanoparticles embedded in hollow hierarchical carbon skeletons. The preparation only involved the fabrication of metal‐organic framework templates and subsequent pyrolysis with the addition of KCl−KBr molten salt, which played a crucial role in pore size extending and metal sintering inhibiting. Benefitting from the encapsulation effect, the as‐synthesized Cu@HHC materials exhibited remarkable catalytic performance and recycling stability in the selective oxidation of biomass‐derived 5‐hydroxymethylfurfural into 2,5‐diformylfuran under mild reaction conditions.
Golden codeword‐based generalized spatial modulation
Authors: Sibanda Nathael , Xu Hongjun , Pillay Narushan 
Published: March 2022

SummaryConventional‐generalized spatial modulation (C‐GSM) is an
multiple‐input multiple‐output (MIMO) spatial modulation (SM) scheme that transmits the same complex amplitude/phase modulation symbol from multiple active transmit antennas. By using two active transmit antennas during a transmission interval, C‐GSM is capable of achieving high spectral efficiencies. However, as the size of the signal constellation/domain increases, the minimum Euclidean distances (ED) between the symbols decrease. Hence, this leads to a degradation of the average bit error rate (ABER) performance of the scheme. Hence, motivated to improve the error performance of C‐GSM schemes, first, this study proposes a new scheme called Golden codeword‐based generalized spatial modulation (GCW‐GSM), which combines C‐GSM and the Golden code to take advantage of the benefits of both while avoiding their drawbacks. The proposed scheme uses conventional quadrature amplitude modulation (C‐QAM), and it is investigated over Rayleigh frequency‐flat fading channels with additive white Gaussian noise. Second, a closed‐form expression of the theoretical average bit error probability of the proposed GCW‐GSM scheme is formulated. Compared to simulation results, it proves to be increasingly tight at high signal‐to‐noise ratio values. Finally, the proposed scheme performance over the Rayleigh‐frequency‐flat fading channel is compared to that over the Rician channel. An improvement in the error performance of
with spectral efficiency of
is seen in
C‐16QAM GCW‐GSM over
C‐256QAM conventional‐spatial modulation and
C‐256QAM C‐GSM schemes at a bit error rate (BER) of
. The
C‐16QAM GCW‐GSM scheme exhibits an improvement in the error performance of
with spectral efficiency of
over the
C‐64QAM conventional quadrature spatial modulation scheme at a BER of
. Finally, the
16‐QAM GCW‐GSM under Rayleigh fading has a performance gain of 3 dB over
16‐QAM GCW‐GSM under Rician fading with a Rician K factor of 3.
New benzothienopyrimidine derivatives as dual EGFR/ARO inhibitors: Design, synthesis, and their cytotoxic effect on MCF‐7 breast cancer cell line
Authors: Sobh Eman A. , Khalil Nadia A. , Faggal Samar I. , Hassan Marwa S. A. 
Published: March 2022

AbstractNew cytotoxic agents based on benzothienopyrimidine scaffold were designed, synthesized, and evaluated against the MCF‐7 breast cancer line in comparison to erlotinib and letrozole as reference drugs. Eight compounds demonstrated up to 20‐fold higher anticancer activity than erlotinib, and five of these compounds were up to 11‐fold more potent than letrozole in MTT assay. The most promising compounds were evaluated for their inhibitory activity against EGFR and ARO enzymes. Compound 12, which demonstrated potent dual EGFR and ARO inhibitory activity with IC50 of 0.045 and 0.146 µM, respectively, was further evaluated for caspase‐9 activation, cell cycle analysis, and apoptosis. The results revealed that the tested compound 12 remarkably induced caspase‐9 activation (IC50 = 16.29 ng/ml) caused cell cycle arrest at the pre‐G1/G1 phase and significantly increased the concentration of cells at both early and late stage of apoptosis. In addition, it showed a higher safety profile on normal MCF‐10A cells, and higher antiproliferative activity on cancer cells (IC50 = 8.15 µM) in comparison to normal cells (IC50 = 41.20 µM). It also revealed a fivefold higher selectivity index than erlotinib towards MCF‐7 cancer cells. Docking studies were performed to rationalize the dual inhibitory activity of compound 12.
Genetic and phenotypic profiling of supranormal ejection fraction reveals decreased survival and underdiagnosed heart failure
Authors: Forrest Iain S. , Rocheleau Ghislain , Bafna Shantanu , Argulian Edgar , Narula Jagat , Natarajan Pradeep , Do Ron 
Published: March 2022

AimsIndividuals with supranormal left ventricular ejection fraction (snLVEF; LVEF >70%) have increased mortality. However, the genetic and phenotypic profile of snLVEF remains unknown. This study aimed to determine the relationship of both snLVEF genetic risk and phenotype with survival and underdiagnosed heart failure (HF).Methods and resultsA snLVEF genetic risk score (GRS) was applied and cases of snLVEF were identified in 486 754 individuals across two population‐based cohorts (BioMe Biobank and UK Biobank). The snLVEF GRS and phenotype were evaluated for association with survival, as well as HF diagnosis, markers, symptoms, and medications. Of 486 754 participants, the median age was 58 years, 20 069 (4.1%) died, and 10 088 (2.1%) had diagnosed HF. Both snLVEF GRS (hazard ratio [HR] 1.1 for top 10% vs. bottom 10% GRS; p = 0.002) and phenotype (HR 1.4; p = 0.003) were associated with increased all‐cause mortality. Both snLVEF GRS and phenotype were associated with reduced HF diagnosis (odds ratio [OR] 0.97 and OR 0.63, respectively; both p ≤0.002). However, the snLVEF GRS and phenotype were both associated with elevated brain natriuretic peptide (BNP) levels (146 and 185 pg/ml increase, respectively; p <0.001), including 268 out of 455 (59%) individuals with snLVEF phenotype who had BNP >100 pg/ml. Among 476 666 participants without HF diagnoses, snLVEF GRS and phenotype were associated with increased HF symptoms (e.g. exertional dyspnoea OR 1.4 and OR 1.3; p <0.003) and HF medications (e.g. loop diuretic OR 1.2 and OR 1.03; p <0.02). Associations were consistent in hypertensive individuals without cardiac comorbidities.ConclusionsGenetic predisposition to and presence of snLVEF are associated with decreased survival and underdiagnosed HF.
Use of evidence‐based therapy in heart failure with reduced ejection fraction across age strata
Authors: Stolfo Davide , Lund Lars H. , Becher Peter Moritz , Orsini Nicola , Thorvaldsen Tonje , Benson Lina , Hage Camilla , Dahlström Ulf , Sinagra Gianfranco , Savarese Gianluigi 
Published: March 2022

AimsIn older patients, guideline‐directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (<40%; HFrEF) is not contraindicated, but adherence to guidelines is limited. We investigated the implementation of GDMT in HFrEF across different age strata in a large nationwide cohort.Methods and resultsPatients with HFrEF and HF duration ≥3 months registered in the Swedish HF Registry between 2000–2018 were analysed according to age. Multivariable logistic and multinomial regressions were fitted to investigate factors associated with underuse/underdosing. Of 27 430 patients, 31% were <70 years old, 34% 70–79 years old, and 35% ≥80 years old. Use of treatments progressively decreased with increasing age. Use of renin–angiotensin system/angiotensin receptor–neprilysin inhibitors, beta‐blockers and mineralocorticoid receptor antagonists was 80%, 88% and 35% in age ≥80 years; 90%, 93% and 47% in age 70–79 years; and 95%, 95% and 54% in age <70 years, respectively. Among patients with an indication, use of implantable cardioverter defibrillator and cardiac resynchronization therapy (CRT) was 7% and 23% in age ≥ 80 years; 22% and 42% in age 70–79 years; and 29% and 50% in age <70 years, respectively. Older patients were less likely treated with target doses or combinations of HF medications. Except for CRT, after extensive adjustments, age was inversely associated with the likelihood of GDMT use and target dose achievement.ConclusionIn HFrEF, gaps persist in the use of medications and devices. In disagreement with current recommendations, older patients remain undertreated. Improving strategies and a more individualized approach for implementing use of GDMT in HFrEF are required, particularly in older patients.
Synthesis of V‐Shaped Bis‐coumarins through Aldol Reaction/Double Lactonization Cascade Reaction from Bis(2‐hydroxyphenyl)methanone and Meldrum's Acid
Authors: Wang Ding , Ma Zhishuang , Xi Jin , Wang Nana , Wang Tao , Liang Yong , Zhang Zunting 
Published: March 2022

AbstractA concise and efficient method was developed for the synthesis of chromeno[3,4‐c]chromene‐6,7‐dione using readily available bis(2‐hydroxyphenyl)methanone and Meldrum's acid. The protocol displays a broad substrate scope and good functional group tolerance, including alkyl, alkoxyl, aryl, and halogens. These π‐extended scaffolds showed blue‐green fluorescence with a large Stokes shift. The photophysical studies revealed that 2‐position substituted chromeno[3,4‐c]chromene‐6,7‐dione caused a significant bathochromic shift.
The Perkin Strategy for the Synthesis of Large Carboxy‐Substituted Polycyclic Aromatic Compounds
Authors: Sturm Ludmilla , Aribot Frédéric , Soliman Luc , Bock Harald , Durola Fabien 
Published: March 2022

AbstractAn efficient and versatile synthetic approach has been developed for the synthesis of large carboxy‐substituted polycyclic arenes. This strategy relies on Perkin reactions between arylacetic and arylglyoxylic acids for the formation of flexible precursors. A subsequent rigidification step, by catalyst‐ or light‐induced intramolecular cyclization reactions, then yields fully condensed polycyclic aromatic compounds. Protection and deprotection techniques have been developed to allow the controlled assembly of a large number of building blocks. This method can now be applied to the formation of planar or non‐planar, linear or macrocyclic species of various sizes.
Objective discrimination of fur type based on electrophoresis optimized for fur‐hair proteins
Authors: Sekimoto Yuri , Tokai Arisa , Aritaki Muneshige , Ando Takeshi , Masuda Takeshi 
Published: March 2022

AbstractThe accurate identification of animal species used for fur is important for conserving endangered animals, stopping illegal fur distribution, and addressing consumer concerns. Animal species used for fur are currently differentiated by observing species‐specific morphological fur‐hair features through a microscope. Although this method is simple, the results may differ among inspectors owing to its subjective nature. To develop an objective approach for differentiating animal species based on fur, we utilized the electrophoretic patterns of fur‐hair proteins. First, we optimized protein extraction methods to produce clear electrophoretic patterns from fur‐hair proteins. Then, we obtained 324 electrophoretic patterns from 54 fur samples belonging to 24 different animals; 216 of the 324 patterns were used for the construction of a discrimination model using two‐way orthogonal partial least squares discriminant analysis. The model correctly discriminated between all the remaining 108 patterns without any false negatives or positives. Moreover, this model could discriminate between fur samples from closely related species that are difficult to distinguish using conventional microscopic identification because of the visual similarity of the fur hairs.
Aqueous electrochemistry: The toolbox for life's emergence from redox disequilibria
Authors: Nitschke Wolfgang , Schoepp‐Cothenet Barbara , Duval Simon , Zuchan Kilian , Farr Orion , Baymann Frauke , Panico Francesco , Minguzzi Alessandro , Branscomb Elbert , Russell Michael J. 
Published: March 2022

AbstractThe second law of thermodynamics leaves no doubt that life on planet Earth and its inherent substantial decrease in entropy is fundamentally based on mechanisms converting environmental free energy into the spatial and temporal order of metabolic processes. This argument holds for present life as much as it does for its very beginnings some 4 billion years ago. In this contribution, we try to strip down free energy conversion in extant life (known as “bioenergetics” to the biologists) to its basic principles with the aim to potentially retrodict the nature of the pre‐biotic precursor which drove life into existence. We demonstrate that these basic principles are deeply rooted in aqueous electrochemistry and strongly rely on inorganic redox compounds. The question of life's emergence, generally considered to fall into the realm of organic chemistry, should therefore rather be recognized as an electrochemical problem and its ultimate elucidation will need to strongly implicate the community of electrochemical scientists.
Modeling of the operating characteristics of photovoltaic modules based on particle swarm optimization
Authors: Provensi Lucas Lima , Grala Gabriel Henrique , Zukeram Junior Emílio Soitsi , Alcantara Glaucio Pedro , Krummenauer Rafael , Andrade Cid Marcos Gonçalves 
Published: March 2022

AbstractThis work evaluates the use of particle swarm optimization to extract the parameters that represent a photovoltaic cell in the model of one diode and five parameters (1D5P) to obtain current versus voltage characteristic curves (I × V) of a photovoltaic module operating under a wide range of temperature and irradiation scenarios. In all the modeling and simulation processes, only information of the module's data sheet provided by the manufacturers was used, without depending on results from other simulations or external data collections. To validate the study, the simulation of the current versus voltage (I × V) curves of a commercial photovoltaic module was made, and this was compared with data provided by the manufacturer and also compared with Chenni's method, which is consolidated by the literature. Errors of less than 0.3% were obtained for the simulations performed under the standard test conditions and in temperature and irradiation situations commonly found in practice, as is the case, of G = 700 W/m2 and Tc = 40°C, the 1D5P method showed an average error of approximately 1%, slightly surpassing the Chenni's method where the error was approximately 1.4%.Statement of Industrial RelevanceIn developing countries, such as Brazil, a significant increase in the portion referring to solar energy in the Brazilian energy grid is noted. As in 2016, this portion was only 0.02%, though in 2020, according to the Brazilian Solar Energy Association (ABSOLAR),1 this portion had an increase of 75 times and reached the value of 1.5%. In addition, ABSOLAR's forecast for 2030 is that solar energy will reach 10% of the Brazilian energy grid. One of the reasons for this is that industrial consumer units are increasingly looking for alternative energy sources due to high energy inflation. Photovoltaic generators are an excellent option for industries because they are clean and sustainable energy.2 It is silent and brings a financial return for the investor. Although, even with all the benefits, the photovoltaic generator has a high acquisition cost, especially for consumer units that demand much energy, as is the case of industries. Thus, correct and precise dimensioning for the photovoltaic generator is necessary. One way to increase the accuracy of dimensioning is to use simulation of the photovoltaic modules, which is the objective of this article.Novelty or SignificanceThe developed method uses the particle swarm optimization with constriction factor to simulate I × V curves of a photovoltaic module for any temperature and irradiation values, using only the module's datasheet information. This study demonstrates that the proposed method presents more accurate results than consolidated methods in the literature, as is the case with the Chenni's method.3