bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-138 is a potent regulator of the heterogenous MYC transcript population in cancers
Authors: Desi Ng , Teh Velda , Tong Qing Yun , Lim Chun You , Tabatabaeian Hossein , Chew Xiao Hong , Sanchez-Mejias Avencia , Chan Jia Jia , Zhang Bin , Pitcheshwar Priyankaa , Siew Bei-En , Wang Shi , Lee Kuok-Chung , Chong Choon-Seng , Cheong Wai-Kit , Lieske Bettina , Tan Ian Jse-Wei , Tan Ker-Kan , Tay Yvonne 
Published: December 2021

Abstract3′UTR shortening in cancer has been shown to activate oncogenes, partly through the loss of microRNA-mediated repression. This suggests that many reported microRNA-oncogene target interactions may not be present in cancer cells. One of the most well-studied oncogenes is the transcription factor MYC, which is overexpressed in more than half of all cancers.MYCoverexpression is not always accompanied by underlying genetic aberrations. In this study, we demonstrate that theMYC3′UTR is shortened in colorectal cancer (CRC). Using unbiased computational and experimental approaches, we identify and validate microRNAs that target theMYCcoding region. In particular, we show that miR-138 inhibits MYC expression and suppresses tumor growth of CRC and hepatocellular carcinoma (HCC) cell lines. Critically, the intravenous administration of miR-138 significantly impedes MYC-driven tumor growth in vivo. Taken together, our results highlight the previously uncharacterized shortening of theMYC3′UTR in cancer, and identify miR-138 as a potent regulator of the heterogenousMYCtranscript population.
Cancer risk across mammals
Authors: Vincze Orsolya , Colchero Fernando , Lemaître Jean-Francois , Conde Dalia A. , Pavard Samuel , Bieuville Margaux , Urrutia Araxi O. , Ujvari Beata , Boddy Amy M. , Maley Carlo C. , Thomas Frédéric , Giraudeau Mathieu 
Published: December 2021

AbstractCancer is a ubiquitous disease of metazoans, predicted to disproportionately affect larger, long-lived organisms owing to their greater number of cell divisions, and thus increased probability of somatic mutations1,2. While elevated cancer risk with larger body size and/or longevity has been documented within species3–5, Peto’s paradox indicates the apparent lack of such an association among taxa6. Yet, unequivocal empirical evidence for Peto’s paradox is lacking, stemming from the difficulty of estimating cancer risk in non-model species. Here we build and analyse a database on cancer-related mortality using data on adult zoo mammals (110,148 individuals, 191 species) and map age-controlled cancer mortality to the mammalian tree of life. We demonstrate the universality and high frequency of oncogenic phenomena in mammals and reveal substantial differences in cancer mortality across major mammalian orders. We show that the phylogenetic distribution of cancer mortality is associated with diet, with carnivorous mammals (especially mammal-consuming ones) facing the highest cancer-related mortality. Moreover, we provide unequivocal evidence for the body size and longevity components of Peto’s paradox by showing that cancer mortality risk is largely independent of both body mass and adult life expectancy across species. These results highlight the key role of life-history evolution in shaping cancer resistance and provide major advancements in the quest for natural anticancer defences.
HELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51
Authors: Anand Roopesh , Buechelmaier Erika , Belan Ondrej , Newton Matthew , Vancevska Aleksandra , Kaczmarczyk Artur , Takaki Tohru , Rueda David S. , Powell Simon N. , Boulton Simon J. 
Published: December 2021

AbstractDNA double-stranded breaks (DSBs) are deleterious lesions, and their incorrect repair can drive cancer development1. HELQ is a superfamily 2 helicase with 3′ to 5′ polarity, and its disruption in mice confers germ cells loss, infertility and increased predisposition to ovarian and pituitary tumours2–4. At the cellular level, defects in HELQ result in hypersensitivity to cisplatin and mitomycin C, and persistence of RAD51 foci after DNA damage3,5. Notably, HELQ binds to RPA and the RAD51-paralogue BCDX2 complex, but the relevance of these interactions and how HELQ functions in DSB repair remains unclear3,5,6. Here we show that HELQ helicase activity and a previously unappreciated DNA strand annealing function are differentially regulated by RPA and RAD51. Using biochemistry analyses and single-molecule imaging, we establish that RAD51 forms a complex with and strongly stimulates HELQ as it translocates during DNA unwinding. By contrast, RPA inhibits DNA unwinding by HELQ but strongly stimulates DNA strand annealing. Mechanistically, we show that HELQ possesses an intrinsic ability to capture RPA-bound DNA strands and then displace RPA to facilitate annealing of complementary sequences. Finally, we show that HELQ deficiency in cells compromises single-strand annealing and microhomology-mediated end-joining pathways and leads to bias towards long-tract gene conversion tracts during homologous recombination. Thus, our results implicate HELQ in multiple arms of DSB repair through co-factor-dependent modulation of intrinsic translocase and DNA strand annealing activities.
Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta
Authors: Ulrich Lorenz , Halwe Nico Joel , Taddeo Adriano , Ebert Nadine , Schön Jacob , Devisme Christelle , Trüeb Bettina Salome , Hoffmann Bernd , Wider Manon , Fan Xiaoyu , Bekliz Meriem , Essaidi-Laziosi Manel , Schmidt Marie Luisa , Niemeyer Daniela , Corman Victor Max , Kraft Anna , Godel Aurélie , Laloli Laura , Kelly Jenna N. , Calderon Brenda M. , Breithaupt Angele , Wylezich Claudia , Berenguer Veiga Inês , Gultom Mitra , Osman Sarah , Zhou Bin , Adea Kenneth , Meyer Benjamin , Eberhardt Christiane S. , Thomann Lisa , Gsell Monika , Labroussaa Fabien , Jores Jörg , Summerfield Artur , Drosten Christian , Eckerle Isabella Anne , Wentworth David E. , Dijkman Ronald , Hoffmann Donata , Thiel Volker , Beer Martin , Benarafa Charaf 
Published: December 2021

AbstractEmerging variants of concern (VOCs) are driving the COVID-19 pandemic1,2. Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S614G in ferrets and two mouse models—the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S614G in naive animals.
Modeling of nitrogen solubility in normal alkanes using machine learning methods compared with cubic and PC-SAFT equations of state
Authors: Madani Seyed Ali , Mohammadi Mohammad-Reza , Atashrouz Saeid , Abedi Ali , Hemmati-Sarapardeh Abdolhossein , Mohaddespour Ahmad 
Published: December 2021

AbstractAccurate prediction of the solubility of gases in hydrocarbons is a crucial factor in designing enhanced oil recovery (EOR) operations by gas injection as well as separation, and chemical reaction processes in a petroleum refinery. In this work, nitrogen (N2) solubility in normal alkanes as the major constituents of crude oil was modeled using five representative machine learning (ML) models namely gradient boosting with categorical features support (CatBoost), random forest, light gradient boosting machine (LightGBM), k-nearest neighbors (k-NN), and extreme gradient boosting (XGBoost). A large solubility databank containing 1982 data points was utilized to establish the models for predicting N2solubility in normal alkanes as a function of pressure, temperature, and molecular weight of normal alkanes over broad ranges of operating pressure (0.0212–69.12 MPa) and temperature (91–703 K). The molecular weight range of normal alkanes was from 16 to 507 g/mol. Also, five equations of state (EOSs) including Redlich–Kwong (RK), Soave–Redlich–Kwong (SRK), Zudkevitch–Joffe (ZJ), Peng–Robinson (PR), and perturbed-chain statistical associating fluid theory (PC-SAFT) were used comparatively with the ML models to estimate N2solubility in normal alkanes. Results revealed that the CatBoost model is the most precise model in this work with a root mean square error of 0.0147 and coefficient of determination of 0.9943. ZJ EOS also provided the best estimates for the N2solubility in normal alkanes among the EOSs. Lastly, the results of relevancy factor analysis indicated that pressure has the greatest influence on N2solubility in normal alkanes and the N2solubility increases with increasing the molecular weight of normal alkanes.
Staphylococcus aureus isolates from Eurasian Beavers (Castor fiber) carry a novel phage-borne bicomponent leukocidin related to the Panton-Valentine leukocidin
Authors: Monecke Stefan , Feßler Andrea T. , Burgold-Voigt Sindy , Krüger Henrike , Mühldorfer Kristin , Wibbelt Gudrun , Liebler-Tenorio Elisabeth M. , Reinicke Martin , Braun Sascha D. , Hanke Dennis , Diezel Celia , Müller Elke , Loncaric Igor , Schwarz Stefan , Ehricht Ralf 
Published: December 2021

AbstractStaphylococcus aureus can be a harmless coloniser, but it can also cause severe infections in humans, livestock and wildlife. Regarding the latter, only few studies have been performed and knowledge on virulence factors is insufficient. The aim of the present study was to study S. aureus isolates from deceased wild beavers (Castor fiber). Seventeen isolates from eleven beavers, found in Germany and Austria, were investigated. Antimicrobial and biocide susceptibility tests were performed. Isolates were characterised using S. aureus-specific DNA microarrays, spa typing and whole-genome sequencing. From two isolates, prophages were induced by mitomycin C and studied by transmission electron microscopy. Four isolates belonged to clonal complex (CC) 8, CC12, and CC398. Twelve isolates belonged to CC1956 and one isolate was CC49. The CC49 and CC1956 isolates carried distinct lukF/S genes related to the Panton-Valentine leukocidin (PVL) from human isolates of S. aureus. These genes were located on related, but not identical, Siphovirus prophages. The beavers, from which those isolates originated, suffered from abscesses, purulent organ lesions and necrotising pneumonia, i.e., clinical manifestations resembling symptoms of severe PVL-associated disease in humans. It might thus be assumed that the “Beaver Leukocidin (BVL, lukF/S-BV)”-positive strains are beaver-specific pathogens, and further studies on their clinical role as well as on a possible transmissibility to other species, including humans, are warranted.
Down-regulating GRP78 reverses pirarubicin resistance of triple negative breast cancer by miR-495-3p mimics and involves the p-AKT/mTOR pathway
Authors: Liu Mian , Yang Jiu , Lv Wuwu , Wang Shuanglian , Du Tao , Zhang Kejing , Wu Yuhui , Feng Xueping 
Published: December 2021

AbstractDue to the lack of known therapeutic targets for triple-negative breast cancer (TNBC), chemotherapy is the only available pharmacological treatment. Pirarubicin (tetrahydropyranyl Adriamycin, THP) is the most commonly used anthracycline chemotherapy agent. However, TNBC has a high recurrence rate after chemotherapy, and the mechanisms of chemoresistance and recurrence are not entirely understood. To study the chemoresistance mechanisms, we first screened compounds on a pirarubicin-resistant cell line (MDA-MB-231R) derived from MDA-MB-231. The drug resistance index of MDA-MB-231R cells was approximately five times higher than that of MDA-MB-231 cells. MDA-MB-231R cells have higher GRP78 and lower miR-495-3p expression levels than MDA-MB-231 cells. Transfecting MDA-MB-231R cells with a siGRP78 plasmid reduced GRP78 expression, which restored pirarubicin sensitivity. Besides, transfecting MDA-MB-231R cells with miR-495-3p mimics increased miR-495-3p expression, which also reversed pirarubicin chemoresistance. Cell counting kit-8 (CCK-8), EdU, wound healing, and Transwell assays showed that the miR-495-3p mimics also inhibited cell proliferation and migration. Based on our results, miR-495-3p mimics could down-regulate GRP78 expression via the p-AKT/mTOR signaling pathway in TNBC cells. Remarkably, chemo-resistant and chemo-sensitive TNBC tissues had opposite trends in GRP78 and miR-495-3p expressions. The lower the GRP78 and the higher the miR-495-3p expression, the better prognosis in TNBC patients. Therefore, the mechanism of pirarubicin resistance might involve the miR-495-3p/GRP78/Akt axis, which would provide a possible strategy for treating TNBC.
A review on the research progress and future development of nano‐modified cellulose insulation paper
Authors: Tang Chao , Chen Rui , Zhang Jinzhu , Peng Xiao , Chen Binghao , Zhang Liusheng 
Published: December 2021

AbstractFocussing on the insulating material of power transformer—cellulose insulation paper, this paper first introduces the basic characteristics and engineering application background of insulation paper. Then, the research progress of improving the mechanical properties, thermal stability and electrical properties of insulation paper by nano modification in recent years is compared, and the promotion mechanism is analysed. In addition, in practical engineering application, the oil–paper composite insulation system composed of insulation paper and insulating oil is used for the internal insulation of oil immersed transformer. Therefore, the influence of modified insulation paper on the performance of oil–paper composite insulation system is analysed. Finally, the newly reported new insulation paper is introduced, and the future development trend of modification of traditional insulation paper is analysed.
Improving DC superimposition characteristics of powder cores by applying coupled inductors in multi‐phase boost converter
Authors: Aoki Tatsuya , Imaoka Jun , Yamamoto Masayoshi , Yoshimoto Kosuke 
Published: December 2021

AbstractIn applications where DC current is superimposed, such as inductors for non‐isolated DC‐DC converters, powder core can be considered as an attractive solution owing to its superior features such as: high saturation flux density, high Curie temperature, and soft‐saturation property. However, in powder cores, a drop of inductance appears prominently due to DC superimposition characteristics. This feature is not a desirable characteristic because it leads to an increase in the inductor ripple current under heavy load, which complicates the thermal design of power semiconductors and capacitors. This paper verifies the improvement of DC superimposition characteristics of powder cores by applying coupled inductors. First, the effect of coupled inductors on the improvement of DC superimposition characteristics is experimentally verified. Second, a measurement method for the DC superimposition characteristics of coupled inductor is proposed. Then, a magnetic circuit model is built using the measurement results. Finally, a coupled analysis of magnetic and electric circuits is performed, and it is confirmed that lower magnetic field operation can be realized by coupled inductors even under heavy load conditions. It has been proven that coupled inductors are effective in improving the DC superposition characteristics of the powder cores.
Three‐stage robust voltage/var optimal control of wind farms at multiple time scales
Authors: Wang Min , Liao Kai , Yang Jianwei , Zheng Shunwei , Lu Dingwen 
Published: December 2021

AbstractIn wind farms, the uncertainty of wind power and the incoordination of multiple time scales increase the difficulty of voltage/var control (VVC), and result in the reactive power output of VVC devices becoming unreasonable. This will decrease the power quality and even cause the voltage collapse of wind farms at large voltage deviations. For these problems, hierarchical control of VVC devices is a promising solution, as VVC devices can adjust the reactive power output in different control strategies. Therefore, this paper proposes a three‐stage robust voltage/var optimal control strategy for wind farms. The robust optimization model is introduced to solve the VVC problem caused by the uncertainty of wind power in this strategy. Besides, compared with traditional VVC strategies, the proposed strategy can coordinate different control stages and VVC devices at multiple time scales by combining centralized and local VVC strategies, which achieves voltage/var optimal control objectives. Simulation results demonstrate the good performance of the proposed strategy in mitigating system voltage violation rate and power loss of the wind farm.
Strategic bidding of a multi‐carrier microgrid in energy market
Authors: Haddadipour Shapour , Amir Vahid , Javadi Saeid 
Published: December 2021

AbstractMicrogrid can contribute to the day‐ahead market by submitting bids to minimize its costs. The bidding problem is challenging due to various uncertainties. Thus, the present study provides a comprehensive optimal bidding strategy to determine the optimal power bids of a multi‐carrier microgrid despite the interdependency of power and gas market prices on the day‐ahead and real‐time markets. In this work, the stochastic energy bidding in the proposed multi‐carrier microgrid is solved via a two‐stage procedure to benefit from day‐ahead and real‐time markets. In the first stage, the operator provides hourly energy bids to the distribution system operator regardless of uncertainty. Then, in the second stage, taking into account the confirmed day‐ahead bids, the multi‐carrier microgrid operator serves to balance the load in the real‐time market stemmed from various uncertain parameters. This problem is solved as mixed‐integer linear programming by CPLEX of the GAMS solver. A scenario reduction method is also employed to burden the complexity of the problem. Numerical results show the usefulness of the proposed model.
Substructures, resonances, and debris streams
Authors: Dodd Emma , Helmi Amina , Koppelman Helmer H. 
Published: December 2021

Context. The local stellar halo of the Milky Way contains the debris from several past accretion events.
Aims. Here we study in detail the structure and properties of nearby debris associated with the Helmi streams, which was originally identified as an overdensity in integrals of motion space.
Methods. We use 6D phase-space information from Gaia EDR3 combined with spectroscopic surveys, and we analyse the orbits and frequencies of the stars in the streams using various Galactic potentials. We also explore how the Helmi streams constrain the flattening, q, of the Galactic dark matter halo.
Results. We find that the streams are split into substructures in integrals of motion space, most notably into two clumps in angular momentum space. The clumps have consistent metallicity distributions and stellar populations, supporting a common progeny. In all the realistic Galactic potentials explored, the Helmi streams’ stars depict a diffuse distribution close to Ωz/ΩR ∼ 0.7. At the same time, the reason for the substructure in angular momentum space appears to be a Ωz : Ωϕ resonance close to 1:1. This resonance is exactly 1:1 in the case where the (density) flattening of the dark halo is q = 1.2. For this halo shape, the substructure in angular momenta is also long-lasting.
Conclusions. Our findings suggest that the structure of the Galactic potential leaves a clear imprint on the properties of phase-mixed debris streams.
The Period-Modulated Harmonic Locked Loop (PM-HLL): A low-effort algorithm for rapid time-domain multi-periodicity estimation
Authors: Hohmann Volker 
Published: December 2021

Many speech and music analysis and processing schemes rely on an estimate of the fundamental frequency f0 of periodic signal components. Most established schemes apply rather unspecific signal models such as sinusoidal models to the estimation problem, which may limit time resolution and estimation accuracy. This study proposes a novel time-domain locked-loop algorithm with low computational effort and low memory footprint for f0 estimation. The loop control signal is directly derived from the input time signal, using a harmonic signal model. Theoretically, this allows for a noise-robust and rapid f0 estimation for periodic signals of arbitrary waveform, and without the requirement of a prior frequency analysis. Several simulations with short signals employing different types of periodicity and with added wide-band noise were performed to demonstrate and evaluate the basic properties of the proposed algorithm. Depending on the Signal-to-Noise Ratio (SNR), the estimator was found to converge within 3–4 signal repetitions, even at SNR close to or below 0 dB. Furthermore, it was found to follow fundamental frequency sweeps with a delay of less than one period and to track all tones of a three-tone musical chord signal simultaneously. Quasi-periodic sounds with shifted harmonics as well as signals with stochastic periodicity were robustly tracked. Mean and standard deviation of the estimation error, i.e., the difference between true and estimated f0, were at or below 1 Hz in most cases. The results suggest that the proposed algorithm may be applicable to low-delay speech and music analysis and processing.
Pulmonary Hypertension and COVID-19
Authors: Castiglione Laura , Droppa Michal 
Published: December 2021

AbstractCoronavirus disease 2019 (COVID-19) is a primary respiratory infectious disease, which can result in pulmonary and cardiovascular complications. From its first appearance in the city of Wuhan (China), the infection spread worldwide, leading to its declaration as a pandemic on March 11, 2020. Clinical research on SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) suggests that the virus may determine changes in the pulmonary hemodynamics through mechanisms of endothelial dysfunction, vascular leak, thrombotic microangiopathy, and venous thromboembolism that are similar to those leading to pulmonary hypertension (PH). Current available studies report echocardiographic signs of PH in approximately 12 to 13% of hospitalized patients with COVID-19. Those with chronic pulmonary obstructive disease, congestive heart failure, pulmonary embolism, and prior PH are at increased risk to develop or worsen PH. Evidence of PH seems to be associated with increased disease severity and poor outcome. Because of the importance of the pulmonary hemodynamics in the pathophysiology of COVID-19, there is growing interest in exploring the potential therapeutical benefits of inhaled vasodilators in patients with COVID-19. Treatment with inhaled nitric oxide and prostacyclin has shown encouraging results through improvement of systemic oxygenation, reduction of systolic pulmonary arterial pressure, and prevention of right ventricular failure; however, data from randomized control trials are still required.