bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzymatic RNA Production from NTPs Synthesized from Nucleosides and Trimetaphosphate**
Authors: Chizzolini Fabio , Kent Alexandra D. , Passalacqua Luiz F. M. , Lupták Andrej 
Published: April 2021

AbstractA mechanism of nucleoside triphosphorylation would have been critical in an evolving “RNA world” to provide high‐energy substrates for reactions such as RNA polymerization. However, synthetic approaches to produce ribonucleoside triphosphates (rNTPs) have suffered from conditions such as high temperatures or high pH that lead to increased RNA degradation, as well as substrate production that cannot sustain replication. Previous reports have demonstrated that cyclic trimetaphosphate (cTmp) can react with nucleosides to form rNTPs under prebiotically‐relevant conditions, but their reaction rates were unknown and the influence of reaction conditions not well‐characterized. Here we established a sensitive assay that allowed for the determination of second‐order rate constants for all four rNTPs, ranging from 1.7×10−6 to 6.5×10−6 M−1 s−1. The ATP reaction shows a linear dependence on pH and Mg2+, and an enthalpy of activation of 88±4 kJ/mol. At millimolar nucleoside and cTmp concentrations, the rNTP production rate is sufficient to facilitate RNA synthesis by both T7 RNA polymerase and a polymerase ribozyme. We suggest that the optimized reaction of cTmp with nucleosides may provide a viable connection between prebiotic nucleotide synthesis and RNA replication.
4‐Nitroanisole Facilitates Proton Reduction: Visible Light‐Induced Oxidative Aryltrifluoromethylation of Alkenes with Hydrogen Evolution
Authors: Kong Rui , Fu Tingfeng , Yang Ruihan , Chen Danna , Liang Deqiang , Dong Ying , Li Weili , Wang Baoling 
Published: April 2021

AbstractA complementary oxidative photocatalytic strategy is presented. In the presence of 4‐nitroanisole, hexafluoroisopropanol (HFIP) as a proton source is activated and the proton photoreduction is enhanced, enabling a range of cyclizative aryltrifluoromethylations of alkenes and CF3SO2Na (Langlois’ reagent) with hydrogen evolution. Such a protocol is general, for both activated and unactivated olefins could be used as the substrates, affording a variety of CF3‐containing heterocycles such as indolines, indolin‐2‐ones, 3,4‐dihydroisoquinolin‐1‐ones, 5,6‐dihydrobenzoimidazo[2,1‐a]isoquinolines, benzoimidazo[2,1‐a]isoquinolin‐6(5H)‐ones and 1,2,3,4‐tetrahydroisoquinolines, under mild and metal‐ and oxidant‐free conditions with a good functional‐group tolerance. Extensive mechanistic investigations revealed that p‐nitroanisole (p‐NA) does not react with the photocatalyst directly as an oxidant, but rather activates HFIP via proton‐coupled electron transfer (PCET) and scavenges some of the reduced protons to improve proton photoreduction.
Morphology of Flashing Feeds at Critical Fluid Properties in Larger Pipes
Authors: Döß Alexander , Schubert Markus , Wiezorek Michael , Hampel Uwe , Flegiel Felix , Windmeier Christoph , Schleicher Eckhard , Schunk Christoph 
Published: April 2021

AbstractTailored conditioning and control of flashing feeds in industrial applications requires knowledge of the evolving flow morphology and phase fractions along the feed pipe. Design methods obtained from reference systems (e.g. water‐air) are hardly applicable for commercial scales and critical fluid properties (e.g. high vapor densities, low surface tension). In this study, the flow morphology of flashing feeds in a novel refrigerant test rig at critical fluid properties was analyzed using wire‐mesh sensors at two locations along the feed pipe and experimental data from the water‐air system.
Recent Advances in Radiometals for Combined Imaging and Therapy in Cancer
Authors: Herrero Álvarez Natalia , Bauer David , Hernández‐Gil Javier , Lewis Jason S. 
Published: April 2021

AbstractNuclear medicine is defined as the use of radionuclides for diagnostic and therapeutic applications. The imaging modalities positron emission tomography (PET) and single‐photon emission computed tomography (SPECT) are based on γ‐emissions of specific energies. The therapeutic technologies are based on β−‐particle‐, α‐particle‐, and Auger electron emitters. In oncology, PET and SPECT are used to detect cancer lesions, to determine dosimetry, and to monitor therapy effectiveness. In contrast, radiotherapy is designed to irreparably damage tumor cells in order to eradicate or control the disease‘s progression. Radiometals are being explored for the development of diagnostic and therapeutic radiopharmaceuticals. Strategies that combine both modalities (diagnostic and therapeutic), referred to as theranostics, are promising candidates for clinical applications. This review provides an overview of the basic concepts behind therapeutic and diagnostic radiopharmaceuticals and their significance in contemporary oncology. Select radiometals that significantly impact current and upcoming cancer treatment strategies are grouped as clinically suitable theranostics pairs. The most important physical and chemical properties are discussed. Standard production methods and current radionuclide availability are provided to indicate whether a cost‐efficient use in a clinical routine is feasible. Recent preclinical and clinical developments and outline perspectives for the radiometals are highlighted in each section.
Stereoselective Access to Antimelanoma Agents by Hybridization and Dimerization of Dihydroartemisinin and Artesunic acid
Authors: Botta Lorenzo , Cesarini Silvia , Zippilli Claudio , Filippi Silvia , Bizzarri Bruno Mattia , Baratto Maria Camilla , Pogni Rebecca , Saladino Raffaele 
Published: April 2021

AbstractA library of five hybrids and six dimers of dihydroartemisinin and artesunic acid has been synthetized in a stereo‐controlled manner and evaluated for the anticancer activity against metastatic melanoma cell line (RPMI7951). Among novel derivatives, three artesunic acid dimers showed antimelanoma activity and cancer selectivity, being not toxic on normal human fibroblast (C3PV) cell line. Among the three dimers, the one bearing 4‐hydroxybenzyl alcohol as a spacer showed no cytotoxic effect (CC50>300 μM) and high antimelanoma activity (IC50=0.05 μM), which was two orders of magnitude higher than that of parent artesunic acid, and of the same order of commercial drug paclitaxel. In addition, this dimer showed cancer‐type selectivity towards melanoma compared to prostate (PC3) and breast (MDA‐MB‐231) tumors. The occurrence of a radical mechanism was hypothesized by DFO and EPR analyses. Qualitative structure activity relationships highlighted the role of artesunic acid scaffold in the control of toxicity and antimelanoma activity.
Examining the ability of the Cancer and Aging Research Group tool to predict toxicity in older men receiving chemotherapy or androgen‐receptor–targeted therapy for metastatic castration‐resistant prostate cancer
Authors: Alibhai Shabbir M. H. , Breunis Henriette , Hansen Aaron R. , Gregg Richard , Warde Padraig , Timilshina Narhari , Tomlinson George , Joshua Anthony M. , Hotte Sebastien , Fleshner Neil , Emmenegger Urban 
Published: April 2021

BACKGROUNDBecause multiple treatments are available for metastatic castrate‐resistant prostate cancer (mCRPC) and most patients are elderly, the prediction of toxicity risk is important. The Cancer and Aging Research Group (CARG) tool predicts chemotherapy toxicity in older adults with mixed solid tumors, but has not been validated in mCRPC. In this study, its ability to predict toxicity risk with docetaxel chemotherapy (CHEMO) was validated, and its utility was examined in predicting toxicity risk with abiraterone or enzalutamide (A/E) among older adults with mCRPC.METHODSMen aged 65+ years were enrolled in a prospective observational study at 4 Canadian academic cancer centers. All clinically relevant grade 2 to 5 toxicities over the course of treatment were documented via structured interviews and chart review. Logistic regression was used to identify predictors of toxicity.RESULTSSeventy‐one men starting CHEMO (mean age, 73 years) and 104 men starting A/E (mean age, 76 years) were included. Clinically relevant grade 3+ toxicities occurred in 56% and 37% of CHEMO and A/E patients, respectively. The CARG tool was predictive of grade 3+ toxicities with CHEMO, which occurred in 36%, 67%, and 91% of low, moderate, and high‐risk groups (P = .003). Similarly, grade 3+ toxicities occurred among A/E users in 23%, 48%, and 86% with low, moderate, and high CARG risk (P < .001). However, it was not predictive of grade 2 toxicities with either treatment.CONCLUSIONSThere is external validation of the CARG tool in predicting grade 3+ toxicity in older men with mCRPC undergoing CHEMO and demonstrated utility during A/E therapy. This may aid with treatment decision‐making.
Colloidal Nanospheres of Amorphous Selenium: Facile Synthesis, Size Control, and Optical Properties
Authors: Cheng Haoyan , Zhou Shan , Xie Minghao , Gilroy Kyle D. , Zhu Zhihong , Xia Younan 
Published: April 2021

AbstractThis article reports a facile method for the colloidal synthesis of nanospheres made of amorphous selenium (ɑ‐Se). The diameters of the nanospheres can be tightly controlled in the range of 45–157 nm by varying the reaction time and temperature, as well as the amount of the reducing agent. The average size of the nanospheres is measured using transmission electron microscopy and dynamic light scattering while their optical properties are characterized using UV‐vis spectroscopy. We also compute their UV‐vis spectra using the discrete dipole approximation (DDA) method and the calculated spectra are consistent with the experimental data based on the UV‐vis spectra and the particle sizes derived from electron microscopy. The data derived from DDA calculations provides a fitting curve for finely controlling the sizes of the ɑ‐Se nanospheres by monitoring the UV‐vis spectra of the reaction solution at different stages of a synthesis.
A Photoionization Reflectron Time‐of‐Flight Mass Spectrometric Study on the Detection of Ethynamine (HCCNH2) and 2H‐Azirine (c‐H2CCHN)
Authors: Turner Andrew M. , Chandra Sankhabrata , Fortenberry Ryan C. , Kaiser Ralf I. 
Published: April 2021

AbstractIces of acetylene (C2H2) and ammonia (NH3) were irradiated with energetic electrons to simulate interstellar ices processed by galactic cosmic rays in order to investigate the formation of C2H3N isomers. Supported by quantum chemical calculations, experiments detected product molecules as they sublime from the ices using photoionization reflectron time‐of‐flight mass spectrometry (PI‐ReTOF‐MS). Isotopically‐labeled ices confirmed the C2H3N assignments while photon energies of 8.81 eV, 9.80 eV, and 10.49 eV were utilized to discriminate isomers based on their known ionization energies. Results indicate the formation of ethynamine (HCCNH2) and 2H‐azirine (c‐H2CCHN) in the irradiated C2H2:NH3 ices, and the energetics of their formation mechanisms are discussed. These findings suggest that these two isomers can form in interstellar ices and, upon sublimation during the hot core phase, could be detected using radio astronomy.
Photoinduced Storage and Thermal Release of Singlet Oxygen from 1,2‐Dihydropyridine Endoperoxides
Authors: De Bonfils Paul , Verron Elise , Nun Pierrick , Coeffard Vincent 
Published: April 2021

AbstractThe quest for molecules able to trap, store, and release singlet oxygen is of utmost interest due to their applicability in various domains such as materials science and photomedicine. The aim of this study was to prepare and study a new family of singlet oxygen donors based on the 1,2‐dihydropyridine motif. The experiments demonstrated the influence of substituents and solvents on the photooxygenation rate constants. The process can be operated reversibly by thermolysis of the in situ formed endoperoxide leading to a release of singlet oxygen and formation of the parent 1,2‐dihydropyridine compound. A bifunctional structure based on a phenalenone photosensitizer covalently connected to a 1,2‐dihydropyridine module was synthesized via a multi‐step sequence. Upon irradiation with blue light, singlet oxygen was produced leading to the formation of the endoperoxide intermediate. In the dark cycle, the endoperoxide underwent cycloreversion reaction affording the parent 1,2‐dihydropyridine unit paving the way to a continuous production of singlet oxygen during the light/dark cycles.
Association between dental diseases and history of stroke in the United States
Authors: Alhadainy Hatem A. , Keefe Thomas , Abdel‐Karim Amany H. , Abdulrab Saleem , Halboub Esam 
Published: April 2021

AbstractObjectiveThis study aimed to determine the potential association between the dental diseases and self‐reported history of stroke in the United States based on data from the Third National Health and Nutrition Examination Survey (NHANES III).MethodsData were extracted from NHANES III. Dental variables were carious tooth surfaces, number of missing teeth, gingival bleeding, and periodontal pockets. Multiple logistic regression modeling was used to estimate the effect of these dental diseases on the self‐reported history of stroke with intent to adjust for the other potential determinants: age, sex, race, marital status, health insurance, education, exercise, body mass index, smoking, alcohol, hypertension, high serum cholesterol, and diabetes.ResultsNumber of missing teeth was found to be significantly associated with the self‐reported history of stroke. Associations between the self‐reported history of stroke and caries, gingival bleeding, or periodontal pockets were not statistically significant.ConclusionsNumber of missing teeth was an independent determinant of the self‐reported history of stroke.
Basophil activation test: Assay precision and BI 1002494 SYK inhibition in healthy and mild asthmatics
Authors: Carstensen Saskia , Benediktus Ewald , Litzenburger Tobias , Hohlfeld Jens M. , Müller Meike 
Published: April 2021

AbstractBackgroundApplication of basophil activation test (BAT) in clinical trials requires assay validity. Whether assay variability differs between healthy and asthmatic subjects is mostly unknown. This study compares basophil stimulation using blood from healthy and asthmatic subjects with or without inhibition of spleen tyrosine kinase (SYK).MethodsWhole blood of healthy and mild asthmatic subjects was stimulated with anti‐dinitrophenyl (DNP) IgE/DNP bovine serum albumin and anti‐IgE. Basophil activation was detected by CD63 and CD203c expression. CD63 expression levels were compared with serum IgE levels. Three operators repeated experiments with three subjects each from both groups at 3 days to observe assay precision. The effect of the SYK inhibitor BI 1002494 was assessed in BAT for both healthy and asthmatic subjects.ResultsBAT was reproducible in both groups. Acceptance criteria of <25% CV were mostly fulfilled. Stimulation with anti‐DNP (p < 0.001, r = −0.80) but not anti‐IgE (p = 0.74, r = 0.05) was related to serum IgE with levels > 200 IU/ml limiting anti‐DNP stimulation. BI 1002494 IC50 values were 497 nM and 1080 nM in healthy and 287 nM and 683 nM in asthmatics for anti‐DNP and anti‐IgE stimulation, respectively.ConclusionBAT, performed with blood from healthy or asthmatic subjects, is a robust test for the measurement of a physiological response in clinical trials. Blood from asthmatic donors with serum IgE > 200 IU/ml is less feasible when using anti‐DNP stimulation. SYK inhibition was not affected by disease status.
Machine learning‐based traffic scheduling techniques for intelligent transportation system: Opportunities and challenges
Authors: Nama Mahima , Nath Ankita , Bechra Nancy , Bhatia Jitendra , Tanwar Sudeep , Chaturvedi Manish , Sadoun Balqies 
Published: April 2021

SummaryThe rise in traffic congestion has become a significant concern in the urban city environment. The conventional traffic control systems with inefficient human resources management fail to control the traffic discipline, leading to increased traffic density and road offenses. However, the intelligent transportation system (ITS) can provide safety, efficiency, and sustainability for large‐scale vehicular traffic dilemmas. ITS unites machine learning with the available traffic control force and performs real‐time police scheduling to ensure the smooth flow of traffic. Many researchers have demonstrated notable work in intelligent traffic police scheduling and deployment using various optimization algorithms. However, the compilation of such praiseworthy work as a whole is still missing. Motivated by these facts, we provide a comprehensive review of the machine learning‐based state‐of‐the‐art technologies that can be used to form a three‐tier solution taxonomy. The first tier describes various tools and technologies that can be utilized to collect traffic data. The second tier highlights the machine learning algorithms and their accuracy, which forms a pattern in the collected data and then yields some crucial information about traffic flow, congestion levels, and so forth. In the third tier, the most vital taxonomy layer, various traffic police scheduling strategies are discussed. The proposed survey also presents the use of cases of traffic police scheduling that elaborates this review's applicability in various domains. Finally, some of the key challenges in the subject being reviewed are discussed, which initiates a further scope of improvement.
TGF‐β superfamily co‐receptors in cancer
Authors: Pawlak John B. , Blobe Gerard C. 
Published: April 2021

AbstractTransforming growth factor‐β (TGF‐β) superfamily signaling via their cognate receptors is frequently modified by TGF‐β superfamily co‐receptors. Signaling through SMAD‐mediated pathways may be enhanced or depressed depending on the specific co‐receptor and cell context. This dynamic effect on signaling is further modified by the release of many of the co‐receptors from the membrane to generate soluble forms that are often antagonistic to the membrane‐bound receptors. The co‐receptors discussed here include TβRIII (betaglycan), endoglin, BAMBI, CD109, SCUBE proteins, neuropilins, Cripto‐1, MuSK, and RGMs. Dysregulation of these co‐receptors can lead to altered TGF‐β superfamily signaling that contributes to the pathophysiology of many cancers through regulation of growth, metastatic potential, and the tumor microenvironment. Here we describe the role of several TGF‐β superfamily co‐receptors on TGF‐β superfamily signaling and the impact on cellular and physiological functions with a particular focus on cancer, including a discussion on recent pharmacological advances and potential clinical applications targeting these co‐receptors.
Transforming growth factor‐beta1 and myeloid‐derived suppressor cells: A cancerous partnership
Authors: Mojsilovic Slavko , Mojsilovic Sonja S. , Bjelica Suncica , Santibanez Juan F. 
Published: April 2021

AbstractTransforming growth factor‐beta1 (TGF‐β1) plays a crucial role in tumor progression. It can inhibit early cancer stages but promotes tumor growth and development at the late stages of tumorigenesis. TGF‐β1 has a potent immunosuppressive function within the tumor microenvironment that largely contributes to tumor cells' immune escape and reduction in cancer immunotherapy responses. Likewise, myeloid‐derived suppressor cells (MDSCs) have been postulated as leading tumor promoters and a hallmark of cancer immune evasion mechanisms. This review attempts to analyze the prominent roles of both TGF‐β1 and MDSCs and their interplay in cancer immunity. Furthermore, therapies against either TGF‐β1 or MDSCs, and their potential synergistic combination with immunotherapies are discussed. Simultaneous TGF‐β1 and MDSCs inhibition suggest a potential improvement in immunotherapy or subverted tumor immune resistance.
Population abundance in arctic grayling using genetics and close‐kin mark‐recapture
Authors: Prystupa Samuel , McCracken Gregory R. , Perry Robert , Ruzzante Daniel E. 
Published: April 2021

AbstractArctic Grayling (Thymallus arcticus) are among the most widely distributed and abundant freshwater fish in the Yukon Territory of Canada, yet little information exists regarding their broad and fine‐scale population structures or the number and size of these populations. The estimation of population abundance is fundamental for robust management and conservation, yet estimating abundance in the wild is often difficult. Here, we estimated abundance of an Arctic Grayling population using multiple genetic markers and the close‐kin mark‐recapture (CKMR) method. A total of N = 1,104 Arctic Grayling collected from two systems in Yukon were genotyped at 38 sequenced microsatellites. We first identified structure and assessed genetic diversity (effective population size, ). Collections from one of the systems (Lubbock River) comprised adults and young‐of‐the‐year sampled independently allowing the identification of parent–offspring pairs (POPs), and thus, the estimation of abundance using CKMR. We used COLONY and CKMRsim to identify POPs and both provided similar results leading to indistinguishable estimates (95% CI) of census size, that is, = 1858 (1259–2457) and 1812 (1229–2389). The accuracy of the population abundance estimates can in the future be improved with temporal sampling and more precise age or size‐specific fecundity estimates for Arctic Grayling. Our study demonstrates that the method can be used to inform management and conservation policy for Arctic Grayling and likely also for other fish species for which the assumption of random and independent sampling of adults and offspring can be assured.
Testing for functional significance of traits: Effect of the light environment in tropical tree saplings
Authors: Modolo Guilherme Silva , dos Santos Victor Alexandre Hardt Ferreira , Ferreira Marciel José 
Published: April 2021

Abstract

Functional traits have been examined to explain the growth rates of forest communities in different sites. However, weak or nonexistent relations are often found, especially due to the following methodological aspects: 1) lack of an environmental context (e.g., light, water, or nutrient supply), 2) use of nonfunctional traits, 3) an approach that does not contemplate phenotypic integration, and 4) neglect of intraspecific variation.

Here we measured relative growth rates, crown, and leaf traits in saplings of six tropical tree species growing in two light environments (Gap and Understory) to test whether contrasting light environments modulates trait–trait and trait–growth relationships. Moreover, we tested whether models that integrate traits of different dimensions of the plant (crown and leaf) improve the strength of trait–growth relations.

Light availability changed both trait–trait and trait–growth relationships. Overall, in Understory, crown traits (crown length and total leaf area) have a stronger effect on growth rates, while physiological traits related to nutrient acquisition (nitrogen concentration), photochemical efficiency (chlorophyll pigments and chlorophyll a fluorescence), and biochemical efficiency (potassium use efficiency) are strong in Gap. Models including multiple traits explained growth rates better in Gap (up to 62%) and Understory (up to 47%), but just in Gap the best model comprises traits that are representative of different dimensions of the plant.

Synthesis. We advanced the knowledge behind the light effects on tree sapling by posit that trait–trait and trait–growth relationships vary across light environments. Therefore, light availability is a key environmental factor to be considered when choosing the set of traits to be measured in functional approach studies using tropical tree saplings. In compliance with the phenotype integration hypothesis, functional traits are better predictors of growth rates when grouped in a set of traits of different dimensions of the plant that represent different functional mechanisms.