bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metastatic Low-Grade Sarcoma with CARS-ALK Fusion Dramatically Responded to Multiple ALK Tyrosine Kinase Inhibitors: A Case Report with Comprehensive Genomic Analysis
Authors: Jiao Xiao-Dong , Liu Ke , Xu Mingyan , Yu Guanzhen , Liu Danni , Huang Tanxiao , Qin Bao-Dong , Liu Ming , Wu Ying , Ling Yan , Liu Jun , He Xi , Wang Liangzhe , Li Yingmei , Chen Shifu , Zang Yuan-Sheng 
Published: September 2020

Abstract

This article reports a case of advanced metastatic low-grade sarcoma. The patient was diagnosed with an inoperable large (14 × 12 cm) lesion on his neck in September 2015 and underwent two ineffective chemotherapies in the following 4 months. Interestingly, although several pathologists could not agree on the histopathological diagnosis, the precise molecular pathological diagnosis was obtained using next-generation sequencing (NGS) and finally brought excellent therapeutic effects. The patient was detected to have CARS-ALK fusion by NGS and then was successfully treated with crizotinib orally. He received surgical resection of primary and metastatic lesions after tumor shrinkage. The combined treatment brought a durable response for 40 months. Although the tumor recurred in July 2019, the patient has been responding well to the second-line ALK tyrosine kinase inhibitor alectinib to date. We performed whole genome sequencing on the patient's primary, metastatic, and recurrent tumors and did comprehensive genomic analysis. Furthermore, our analysis results revealed that a whole genome duplication event might have happened during tumorigenesis of this case.

Key Points
To our best knowledge, this is the first report of a very successful treatment with first- and second-line ALK tyrosine kinase inhibitors for CARS-ALK fusion–positive metastatic low-grade sarcoma. Molecular pathological result can guide precision treatment for sarcoma, even when the exact histopathology cannot be obtained. Multiple samples from this patient were analyzed using whole genome sequencing. Results provided detailed genomic characteristics and showed tumor evolution of this low-grade sarcoma case. A whole genome duplication event might have happened during tumorigenesis of this low-grade sarcoma case.
Morphology and mechanical properties of poly (acrylonitrile‐butadiene‐styrene)/multi‐walled carbon nanotubes nanocomposite specimens prepared by fused deposition modeling
Authors: Razavi‐Nouri Mohammad , Rezadoust Amir Masood , Soheilpour Zahra , Garoosi Keyvan , Ghaffarian Seyed Reza 
Published: September 2020

AbstractIn this work, poly(acrylonitrile‐butadiene‐styrene) (ABS) filaments containing 0, 1, 3, and 5 wt% multi‐walled carbon nanotubes (MWCNT) were prepared by extrusion. The filaments were then used to make the required specimens with a fused deposition modeling machine. The results obtained from the tensile measurements revealed that with the increase in the layer thickness, the tensile strength of the printed specimens decreased; however, the raster angle did not have any significant effect on the properties. The transmission electron microscope images showed that for the sample containing 3 wt% MWCNT, nanoparticles were reasonably dispersed throughout the matrix. The scanning electron microscope images illustrated that the size of the voids formed within the specimens was increased with increasing of the layer thickness from 0.05 to 0.2 mm. It was also found that the maximum properties could be obtained by using the layer thickness, raster angle and MWCNT concentration of 0.05 mm, 45/−45°, and 3 wt%, respectively. The results showed that both the tensile strength and elastic modulus of the filaments progressively increased with the increase of the nanofiller content in the range studied. It was found that for the constant layer thickness of 0.05 mm, all the specimens printed with single raster angles of 0, 45, and 90° showed higher tensile strength in comparison with their counterparts printed with two raster angles of 0/90° and 45/−45°.
Prediction of process parameters of water‐assisted injection molding based on inverse radial basis function neural network
Authors: Yang Jiangen , Yu Shengrui 
Published: September 2020

AbstractBecause of the introduction of new processing parameters in water‐assisted injection molding (WAIM), processes control has become more difficult. First, design of experiment (DOE) was carried out by using optimized Latin hypercubes (Opt LHS). On the basis of this, computational fluid dynamics (CFD) method was used to simulate and calculate hollowed core ratios and wall thickness differences of cooling water pipe at different positions. Then inverse radial basis function (RBF) neural network model reflecting the fitting relationship between processing parameters and molding quality was established, and accuracy of the model was detected by cross validation. Finally, expected molding quality was applied to predict processing parameters, and the obtained molding quality under the predicted processing parameters was verified by computer aided engineering (CAE) simulation and experimental methods. The results showed that mean relative precisions of processing parameters such as melt temperature, delay time, short shot size, water pressure, and mold temperature for inverse RBF model were 98.6%, 93.6%, 98.5%, 93.9%, and 97.9%, respectively, which met the accuracy requirements. Furthermore, compared with expected values of hollowed core ratios and wall thickness differences, the average errors of CAE and experiment were 2.3% and 4.9%, respectively.
Opportunities and challenges of pharmacotherapy for pulmonary arterial hypertension in children
Authors: Kam Charissa W. , Ruiz Fadel E. 
Published: October 2020

AbstractPediatric pulmonary hypertension (PAH) is a rare disease that carries a poor prognosis if left untreated. Although there are published guidelines for the treatment of children with pulmonary hypertension, due to the limited number of robust pediatric clinical trials, recommendations are often based on limited data or clinical experience. Furthermore, many practical aspects of care, particularly for the pediatric patient, are learned through experience and best navigated with a multidisciplinary team. While newer PAH therapies have been approved for adults, there is still limited but expanding experience in pediatrics. This new information will help improve the targets of goal‐oriented therapy. Lastly, this review highlights practical aspects in the use of the different therapies available for the treatment of pediatric pulmonary hypertension.
Small Flux Superpotentials for Type IIB Flux Vacua Close to a Conifold
Authors: Álvarez‐García Rafael , Blumenhagen Ralph , Brinkmann Max , Schlechter Lorenz 
Published: October 2020

AbstractWe generalize the recently proposed mechanism by Demirtas, Kim, McAllister and Moritz[1] for the explicit construction of type IIB flux vacua with to the region close to the conifold locus in the complex structure moduli space. For that purpose tools are developed to determine the periods and the resulting prepotential close to such a codimension one locus with all the remaining moduli still in the large complex structure regime. As a proof of principle we present a working example for the Calabi‐Yau manifold .[24]
Structural fluctuations and mechanical stabilities of the metamorphic protein RfaH
Authors: Seifi Bahman , Aina Adekunle , Wallin Stefan 
Published: September 2020

AbstractRfaH is a compact two‐domain bacterial transcription factor that functions both as a regulator of transcription and an enhancer of translation. Underpinning the dual functional roles of RfaH is a partial but dramatic fold switch, which completely transforms the ~50‐amino acid C‐terminal domain (CTD) from an all‐α state to an all‐β state. The fold switch of the CTD occurs when RfaH binds to RNA polymerase (RNAP), however, the details of how this structural transformation is triggered is not well understood. Here we use all‐atom Monte Carlo simulations to characterize structural fluctuations and mechanical stability properties of the full‐length RfaH and the CTD as an isolated fragment. In agreement with experiments, we find that interdomain contacts are crucial for maintaining a stable, all‐α CTD in free RfaH. To probe mechanical properties, we use pulling simulations to measure the work required to inflict local deformations at different positions along the chain. The resulting mechanical stability profile reveals that free RfaH can be divided into a “rigid” part and a “soft” part, with a boundary that nearly coincides with the boundary between the two domains. We discuss the potential role of this feature for how fold switching may be triggered by interaction with RNAP.
Protective effect of tolvaptan against cyclophosphamide‐induced nephrotoxicity in rat models
Authors: El‐Shabrawy Mohamed , Mishriki Amal , Attia Hisham , Emad Aboulhoda Basma , Emam Mohamed , Wanas Hanaa 
Published: September 2020

AbstractCyclophosphamide (CP) is a chemotherapeutic agent which is extensively used in the treatment of multiple neoplastic and nonneoplastic diseases like breast cancer, lymphomas, systemic lupus erythematosus, and multiple sclerosis. Dose‐limiting side effects, mainly nephrotoxicity is a major problem hindering its use in the clinical practice. CP induces nephrogenic syndrome of inappropriate antidiuresis mostly via the activation of arginine vasopressin V2 receptors. Moreover, CP produces reactive metabolites which is responsible for augmentation of lipid peroxidation and oxidative stress. Tolvaptan (TOL) is a selective vasopressin V2 receptor antagonist used in the treatment of clinically significant hyponatremia, volume overload in heart failure, and liver cirrhosis with edema. The present study aimed to investigate the potential protective effect of TOL in CP‐induced nephrotoxicity. Twenty‐four adult male albino rats were randomly divided into four groups: the control group, TOL group that treated daily with tolvaptan (10 mg/kg/d, orally), CP group where CP was administered intraperitoneally 75 mg/kg on days 3, 4, 5, 19, 20, and 21 of study, and the CP + TOL group where animals were treated with TOL daily with (10 mg/kg/d, orally) for 22 days with concomitant administration of CP as described before. Coadministration of TOL with CP induces significant improvement in the level of urine volume, serum Na+, serum osmolarity, urinary creatinine, and free water clearance in addition to significant reduction of body weight, serum creatinine, urea, serum K+, blood pressure, urine osmolarity, and the fractional excretion of sodium as compared to CP‐treated group. In addition, coadministration of TOL significantly reduced MDA, the marker of lipid peroxidation, and different pro‐inflammatory cytokines. Histopathological changes showed improvement in the signs of nephrotoxicity with the coadministration of TOL. Also, co‐treatment with TOL significantly decreased the level of markers of apoptosis as caspase‐3 and Bax with increased expression of antiapoptotic Bcl‐2 in renal tissue as compared to CP‐treated group.
An evaluation of methods for normalizing diffusion‐based covariance operators in variational data assimilation
Authors: Weaver Anthony T. , Chrust Marcin , Ménétrier Benjamin , Piacentini Andrea 
Published: September 2020

AbstractDeveloping effective ways to model and cycle the background‐error covariance matrix is an active area of research in data assimilation. An important aspect of this problem when using a filter to model the background‐error correlations is the computation of normalization factors to ensure that the diagonal elements of the modelled correlation matrix are all equal to one. Updating the parameters of a flow‐dependent correlation model on each assimilation cycle requires updating the normalization factors, which is costly using traditional methods such as randomization. In this article, we discuss the normalization problem within the context of a diffusion filter‐based covariance model used for background‐error modelling in a variational data assimilation system for the global ocean. We evaluate various methods for estimating normalization factors when the diffusion tensor of the correlation model is derived from an ensemble of ocean states. Our results show that estimates produced using inexpensive methods derived from analytical considerations of the diffusion equation can have significant errors, especially near boundaries. Estimates obtained using randomization with a small sample size (∼100) are more accurate in a globally averaged sense but are noisy and can have unacceptably large errors locally. Next, we focus on the specific problem of accounting for flow‐dependent correlation parameters in the vertical component of the diffusion operator only, which is especially important near the surface for the assimilation of sea surface temperature observations. Remarkably accurate estimates are obtained by approximating the normalization matrix as a separable product of two normalization matrices: one computed using randomization with the horizontal diffusion operator only and the other computed using randomization with the vertical diffusion operator only. If the parameters of the horizontal component of the diffusion operator are static, then only the normalization factors of the flow‐dependent vertical component need to be recomputed on each cycle. This result is of significant practical interest since the vertical diffusion operator employs an inexpensive direct solver and thus can be applied on each cycle with a large random sample to obtain a good approximation of the normalization matrix.
Design and development of a compact thermal ionization mass spectrometer for isotope ratio measurement of uranium
Authors: Bhatia Rajender Kumar , Yadav Varun Kant , Gulhane Milind Manoharrao , Datta Rabi , Joshi Kuldip Devidas , Kasbekar Ajay Mahadeo , Das Subrata , Sreeramulu Konjeti , Saha Tushar Kanti , Ravisankar Edakkunni , Nataraju Vogirala 
Published: October 2020

RationaleA new compact thermal ionization (TI) mass spectrometer, for the isotope ratio analysis of the elements relevant to nuclear applications, has been designed and developed. The new development offers superior performance in terms of sensitivity, precision and a compact footprint in comparison with the conventional one. The main feature of the TI mass spectrometer is the magnetic sector analyser with a sector radius of 20 cm (instead of 30/27 cm in conventional/commercial geometry). An apparent reduction in dispersion has been adequately compensated by employing variable dispersion zoom optics (VDZO).MethodsThe theoretical calculations were validated by computer simulations using SIMION 7.0, leading to the finalization of the mechanical design. Experimental evaluation was carried out using standard TI mass spectrometric methodology to determine the parameters, namely peak flatness, mass range, sensitivity, abundance sensitivity, resolution and precision.ResultsThe multi‐collector resolution was 496, and the maximum mass was m/z 382. The sensitivity for uranium was found to be better than 1 ion for 500 atoms, and an abundance sensitivity of 50 ppm at m/z 237 was obtained. The peak flatness for the uranium peak was 3200 ppm of mass. The precision for the isotopic ratio 235U/238U was found to be 0.05% for the U200 standard.ConclusionsA new compact TI mass spectrometer with a 20 cm sector radius has been designed and developed. The advantage of larger dispersion produced by the VDZO (developed in‐house) was exploited when deciding the 20 cm sector radius. The comparison study with the conventional TI mass spectrometer shows an enhanced (1.5×) sensitivity and an improved precision (0.05%) for the 235U/238U ratio of U200.
Application of 5G new radio for satellite links with low peak‐to‐average power ratios
Authors: Saarnisaari Harri , de Lima Carlos 
Published: September 2020

SummaryThe aim of the paper is to consider feasibility of 5G new radio (NR) over satellite links also known as nonterrestrial networks (NTNs). Large propagation delay and Doppler frequency shift are challenges like is high peak‐to‐average power ratio (PAPR) of 5G NR signal because satellite systems would like to operate at very low‐power amplifier back‐off values. This paper provides a brief summary of progress made in initial synchronization and uplink random access process both in the literature and standardization. Furthermore, the paper explains what is the relationship between low PAPR and power amplifier back‐off and the density of reference symbols by showing that 2‐dB back‐off values can be attained using sufficient reference symbol density. Finally, open issues that need clarification are listed. Interestingly, all solutions to these problems do not mean changes in the standard but proper actions from vendors and operators.
Synthesis of Tantalum Powders in KBr−NaBr and KI−NaI Melts Using Electrochemical Pulverization
Authors: Shmygalev Alexander S. , Isakov Andrey V. , Zaikov Yurii P. , Chernyshev Aleksandr A. 
Published: October 2020

AbstractIn the present work, the possibility for obtaining tantalum powders by means of the electrochemical pulverization (secondary reduction) in the molten electrolytes KBr‐NaBr and KI‐NaI was demonstrated. The powders were analyzed using the X‐ray diffraction, BET, ICP, and laser light scattering. It was revealed that the obtained powders have a chemical purity of 99.98 wt %, which corresponds to the qualification of high‐purity tantalum. The maximum specific surface area of the powder was 17.84 m2/g, and the prevailing particle sizes were in the range from 1.9 to 4.5 μm. The dependence of the predominant particle size on the anion sublattice size was established. The smallest particles were found to be obtained in the systems based on alkali chlorides, the largest in iodide systems.
An Efficient and Facile Synthesis of Deuterium‐Labeled D‐Glycerolphosphocholine and 2,3‐Dilinoleoyl‐sn‐glycero‐3‐phosphocholine
Authors: Gao Yong , Zhang Yinsheng 
Published: October 2020

AbstractStable isotope‐labeled polyene phosphatidylcholines (PCs) were required for quantitative bioanalytical assays of products extracted from soybeans. A facile and efficient method for the synthesis of both [D9] and [D13]2,3‐dilinoleoyl‐sn‐glycero‐3‐phosphocholine ([D9] & [D13]DLPC) in excellent yields and high isotope‐enrichment has been developed applying cheap and commercially available glycine, 2‐aminoethanol and iodomethane‐d3 (99 %, 2H) as starting materials and deuterium sources. [D9]DLPC and [D13]DLPC can be used as an internal standard and/or as a surrogate analyte.
Quantitative Analysis of Anatase‐Rutile Mixtures by Raman Spectroscopy
Authors: Cao Guoqiang , Yi Nan 
Published: October 2020

AbstractWe present how to calculate the weight fraction of anatase in the physical anatase‐rutile mixture based on the analysis of Raman spectra. Raman‐based correlation is also applicable to characterize quantitively the weight fraction of anatase from chemically synthesized anatase‐rutile titanium dioxide mixtures.
Anticancer Activity of 3,3′‐Diindolylmethane and the Molecular Mechanism Involved in Various Cancer Cell Lines
Authors: Koli Papita , Reena  , Indurthi Harish K. , Sharma Deepak K. 
Published: October 2020

AbstractIndole‐3‐carbinol is a natural compound present in cruciferous plants, which upon digestion, converts into 3,3′‐diindolylmethane (DIM) under acidic pH of the stomach. In recent years, various methods have been developed to improve the synthesis of DIM and its analogs because of different pharmacological activities like anticancer, antimicrobial, anti‐inflammatory, etc. Among them, DIMs anticancer activity by modulation of protein expression in cell signaling pathways and other factors has widely studied. This review describes the antiproliferative activity of DIMs and its mode of action, which resulted in apoptosis in various cancerous cells. We have performed a literature search on DIMs anticancer activity over the last ten years (2011–2020) and reported in this review. Several fascinating DIM attributes against cancer suggest it as a potential candidate for further drug development programs. This review will guide the medicinal chemist to find the mechanistic pathways involved in the inhibition of proliferation in cancerous cells by novel DIMs.
Computational Identification of a New Adsorption Site of CO2 on the Ag (211) Surface
Authors: Guo Shuai , Li Yao , Liu Lei , Liu Licheng , Zhang Xiangping , Zhang Suojiang 
Published: October 2020

AbstractNowadays, electrochemical reduction of CO2 has been considered as an effective method to solve the problem of global warming. The primary challenge in studying the mechanism is to determine the adsorption states of CO2, since complicated metal surfaces often result in many different adsorption sites. Based on the density functional theory (DFT) calculations, we performed a computational study on the adsorption of CO2 on the Ag electrode surface. The results show that the adsorption populations of CO2 are extremely sensitive to the adsorption sites. Importantly, we found a new preferable adsorption position which is the step site of the (211) surface, having both oxygen atoms interacting with Ag atoms. Moreover, the adsorption populations were found with the order of (211)>(110)>(111)>(100). Subsequently, the adsorption characteristics were correlated with p orbital energies, the d‐band positions and charge transfers between Ag surfaces and CO2.
The evolution of cooperation in the face of conflict: Evidence from the innovation ecosystem for mobile telecom standards development
Authors: Jones Stephen L. , Leiponen Aija , Vasudeva Gurneeta 
Published: October 2020

AbstractResearch SummaryHow does interfirm cooperation in innovation ecosystems evolve in the face of conflict? We theorize that conflict propels firms to reconfigure cooperative relationships while maintaining and even increasing cooperation with aggressors because cooperation is the primary mechanism for value creation in such ecosystems. To empirically test our arguments, we study patent litigation and subsequent cooperation between mobile telecommunications firms within the 3GPP standards development organization. We find evidence of a dual cooperative strategy in the face of conflict: while cooperation increases between litigants, defendants also enhance cooperation with others to steer standards away from aggressors. We also highlight the contingent roles of technological complementarities and relational position underpinning cooperation after conflict. Our findings demonstrate that in innovation ecosystems, cooperation with adversaries persists despite conflict.Managerial SummaryFirms in innovation‐driven industries cooperate to develop interoperability standards and compatible technologies. Yet, cooperative firms may disagree about what constitutes fair, reasonable, and non‐discriminatory terms for licensing intellectual property. Thus, conflict and patent litigation arise even as firms cooperate to build technologies and industry standards. We find that in innovation ecosystems, firms commonly increase cooperative efforts in response to conflict. Less‐connected firms or those with valuable complementary technologies will likely expand cooperation than well‐connected firms or technological competitors. Well‐connected firms may pursue alternative cooperative opportunities. We suggest that defendant firms' managers can adopt a dual cooperative strategy: (a) identify private and shared benefits from the joint development of complementary technologies with aggressors and (b) invest in alternative technological partnerships to influence the direction of future standards development.