bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorescently Labelled ATP Analogues for Direct Monitoring of Ubiquitin Activation
Authors: Hammler Daniel , Stuber Katrin , Offensperger Fabian , Scheffner Martin , Zumbusch Andreas , Marx Andreas 
Published: March 2020

AbstractSimple and robust assays to monitor enzymatic ATP cleavage with high efficiency in real‐time are scarce. To address this shortcoming, we developed fluorescently labelled adenosine tri‐, tetra‐ and pentaphosphate analogues of ATP. The novel ATP analogues bear — in contrast to earlier reports — only a single acridone‐based dye at the terminal phosphate group. The dye's fluorescence is quenched by the adenine component of the ATP analogue and is restored upon cleavage of the phosphate chain and dissociation of the dye from the adenosine moiety. Thereby the activity of ATP‐cleaving enzymes can be followed in real‐time. We demonstrate this proficiency for ubiquitin activation by the ubiquitin‐activating enzymes UBA1 and UBA6 which represents the first step in an enzymatic cascade leading to the covalent attachment of ubiquitin to substrate proteins, a process that is highly conserved from yeast to humans. We found that the efficiency to serve as cofactor for UBA1/UBA6 very much depends on the length of the phosphate chain of the ATP analogue: triphosphates are used poorly while pentaphosphates are most efficiently processed. Notably, the novel pentaphosphate‐harbouring ATP analogue supersedes the efficiency of recently reported dual‐dye labelled analogues and thus, is a promising candidate for broad applications.
NRG/RTOG 1122: A phase 2, double‐blinded, placebo‐controlled study of bevacizumab with and without trebananib in patients with recurrent glioblastoma or gliosarcoma
Authors: Lee Eudocia Q. , Zhang Peixin , Wen Patrick Y. , Gerstner Elizabeth R. , Reardon David A. , Aldape Kenneth D. , deGroot John F. , Pan Edward , Raizer Jeffrey J. , Kim Lyndon J. , Chmura Steven J. , Robins H. Ian , Connelly Jennifer M. , Battiste James D. , Villano John L. , Wagle Naveed , Merrell Ryan T. , Wendland Merideth M. , Mehta Minesh P. 
Published: March 2020

BackgroundTargeting vascular endothelial growth factor (VEGF) alone does not improve overall survival (OS) in recurrent glioblastoma (rGBM). The angiopoiein (Ang)–TIE2 system may play a role in tumor survival under VEGF inhibition. We conducted a phase 2, double‐blinded, placebo‐controlled trial of bevacizumab plus trebananib (a novel Fc fusion protein that sequesters Ang1/Ang2) over bevacizumab alone in rGBM.MethodsPatients ≥18 years of age with a Karnofsky performance status ≥70 and GBM or variants in first or second relapse were randomized to bevacizumab 10 mg/kg every 2 weeks plus trebananib 15 mg/kg every week or bevacizumab plus placebo. The primary endpoint was 6‐month progression‐free survival (PFS).ResultsAfter an initial 6‐patient lead‐in cohort confirmed the safety of combining bevacizumab and trebananib, 115 eligible patients were randomized to the control (n = 58) or experimental treatment (n = 57). In the control arm, 6‐month PFS was 41.1%, median survival time was 11.5 months (95% CI, 8.4‐14.2 months), median PFS was 4.8 months (95% CI, 3.8‐7.1 months), and radiographic response (RR) was 5.9%. In the experimental arm, 6‐month PFS was 22.6%, median survival time was 7.5 months (95% CI, 6.8‐10.1 months), median PFS was 4.2 months (95% CI, 3.7‐5.6 months), and RR was 4.2%. The rate of severe toxicities was not significantly different between arms.ConclusionThe combination of bevacizumab and trebananib was well tolerated but did not significantly improve 6‐month PFS rate, PFS, or OS for patients with rGBM over bevacizumab alone. The shorter PFS in the experimental arm with a hazard ratio of 1.51 (P = .04) suggests that the addition of trebananib to bevacizumab is detrimental.
Trajectories of sickness absence and disability pension in the 2 years before and 3 years after breast cancer diagnosis: A Swedish longitudinal population‐based cohort study
Authors: Chen Lingjing , Alexanderson Kristina A. E. 
Published: March 2020

BackgroundAfter breast cancer (BC) diagnosis, work incapacity often occurs among working‐age women. We investigated the trajectories of previous and subsequent sickness absence and/or disability pension (SA/DP) days, and risk factors for consistently high levels of future SA/DP among these women.MethodsThis longitudinal cohort study included all 3536 women in Sweden aged 19‐64 years who received a first BC diagnosis in 2010. Their annual SA/DP net days from 2 years before to 3 years after diagnosis were calculated. SA/DP patterns were depicted by a group‐based trajectory model. Logistic regressions were used to calculate odds ratios (ORs) with 95% CIs of >90 or >180 SA/DP days/year.ResultsThree trajectories of SA/DP days/year were identified: increasing only in year+1 (61% of all), increasing then decreasing in year+3 (30%), and constantly very high (9%). The risk factors associated with annual SA/DP days >90 (long) and >180 days (extreme long) were similar. Factors associated with having >90 SA/DP days for years 1‐3 were: stage II (OR, 4.59; 95% CI, 2.98‐7.07), stage III+IV (OR, 26.57; 95% CI, 13.52‐52.22), prediagnosis SA 1‐30 days (OR, 2.73; 95% CI, 1.30‐5.70), prediagnosis SA >90 days (OR, 24.52; 95% CI, 12.25‐49.08), and prediagnosis DP (OR, 659.97; 95% CI, 292.52‐>999.99). Conversely, adjusting for prediagnosis SA/DP and stage, sociodemographic factors were not associated with high levels of SA/DP.ConclusionAfter BC diagnosis, SA/DP increased significantly but then decreased. The absolute majority had no SA/DP during year 3. Advanced cancer stage and previous high SA/DP rendered the greatest risk for future high SA/DP. More knowledge is needed for applying the information in rehabilitation and return‐to‐work planning.
Xylem vessel‐diameter–shoot‐length scaling: ecological significance of porosity types and other traits
Authors: Olson Mark , Rosell Julieta A. , Martínez‐Pérez Cecilia , León‐Gómez Calixto , Fajardo Alex , Isnard Sandrine , Cervantes‐Alcayde María Angélica , Echeverría Alberto , Figueroa‐Abundiz Víctor A. , Segovia‐Rivas Alí , Trueba Santiago , Vázquez‐Segovia Karen 
Published: March 2020

AbstractFlowering plants predominantly conduct water in tubes known as vessels, with vessel diameter playing a crucial role in plant adaptation to climate and reactions to climate change. The importance of vessels makes it essential to understand how and why vessel diameter, plant height, and other ecological factors are interrelated. Although shoot length is by far the main driver of variation in mean vessel diameter across angiosperms, much remains to be understood regarding the factors accounting for the abundant variation around they‐axis in plots of mean species vessel diameter against shoot length. Here, we explore the potential role of porosity types, wood density, leaf phenology, background imperforate tracheary element type, vasicentric tracheids, vascular tracheids, perforation plate type, and successive cambia in causing variation in they‐intercept or slope of the mean species vessel‐diameter– and vessel‐density–shoot‐length associations at the shoot tip and base. We detected numerous cases of ecologically significant variation. For example, latewood vessels of ring porous species scale with a lower slope than earlywood, i.e., latewood vessels are relatively narrow in taller plants. This pattern is likely the result of selection favoring freezing‐induced embolism resistance via narrow vessels. Wood density was negatively associated with vessel diameter, with low wood density plants having wider vessels for a given height. Species with scalariform perforation plates scale with a lower shoot base vessel‐diameter–shoot‐length slope, likely reflecting selection against scalariform plates in wide vessels. In other cases, functional groups scaled similarly. For example, species with successive cambia did not differ from those with conventional single cambia in their mean vessel‐diameter–shoot‐length scaling, rejecting our prediction that species with successive cambia should have narrower vessels for a given shoot length. They did, however, have fewer vessels per unit shoot cross‐sectional area than plants of similar heights, likely because vessels have longer functional lifespans (and therefore are fewer) in species with successive cambia. Our methods illustrate how vessel diameter can be studied taking shoot length into account to detect ecologically important variation and construct theory regarding plant adaptation via the hydraulic system that includes plant size as a vital element.
Experimental study of the co‐gasification of wood and polyethylene in a two‐stage gasifier
Authors: Harouna Ibrahim G. , Berger Benjamin , Hervé Jeanmart , Sanogo Oumar , Daho Tizane , Ouiminga Salifou K. , Koulidiati Jean 
Published: March 2020

AbstractCo‐gasification of wood mixed with 20% (mass fraction) of polyethylene (PE) in a two‐stage NOTAR® fixed‐bed gasifier was studied in the present paper. The ratio of air flow injected in the pyrolyzer and air flow injected in the oxidation zone is called the air ratio (AR). The AR of 0.35, 0.43, and 0.49 were used for test runs. Mass and energy balances were established. The study showed the feasibility of co‐gasification of wood mixed with 20% of PE in the two‐stage gasifier. However, considerable quantity of residues rich in fixed carbon content (17% of the fuel mass and 69% of fixed carbon content) was produced due to a low reactivity of the charcoal obtained after the pyrolysis. AR increasing reduces the gas CO content due to overconsumption of char at the pyrolysis stage. H2 and CH4 highest values are obtained for the intermediate AR = 0.43 which maximized the LHV, energy efficiency, and carbon conversion with respectively 4674 kJ/Nm3, 64.35%, and 74.52%. Low reactivity and carbon content of the pyrolysis char likely lead to lower performance of co‐gasification of PE mixed with wood compared to wood gasification.
Simulation of compressibility of entrapped air in an incompressible free surface flow using a pressure‐based method for unified equations
Authors: Shin Sangmook 
Published: March 2020

SummaryA pressure‐based method is developed to solve the unified conservation laws for incompressible and compressible fluids. A polytropic law is used to model the compressibility of a gas and decouple the energy equation. The pressure field is calculated by solving a single‐pressure Poisson equation for the entire flow domain. The effects of the compressibility of the gas are reflected in the source term of the Poisson equation. The continuities of pressure and normal velocity across a material interface are achieved without any additional treatment along the interface. To validate the developed method, the oscillation of a water column in a closed tube due to the compression and expansion of air in the tube is simulated. The computed time history of the pressure at the end wall of the tube is in good agreement with other computational results. The free drop of a water column in a closed tank is simulated. The time history of the pressure at the center of the bottom of the tank shows good agreement with other reported results. The developed code is applied to simulate the air cushion effect of entrapped air in a dam break flow. The computed result is in good agreement with other experimental and computational results until the air is entrapped. As the entrapped air pocket undergoes rapid pulsation, the pressure field of water around the air pocket oscillates synchronously.
Sparse Bayesian vector autoregressions in huge dimensions
Authors: Kastner Gregor , Huber Florian 
Published: March 2020

AbstractWe develop a Bayesian vector autoregressive (VAR) model with multivariate stochastic volatility that is capable of handling vast dimensional information sets. Three features are introduced to permit reliable estimation of the model. First, we assume that the reduced‐form errors in the VAR feature a factor stochastic volatility structure, allowing for conditional equation‐by‐equation estimation. Second, we apply recently developed global–local shrinkage priors to the VAR coefficients to cure the curse of dimensionality. Third, we utilize recent innovations to sample efficiently from high‐dimensional multivariate Gaussian distributions. This makes simulation‐based fully Bayesian inference feasible when the dimensionality is large but the time series length is moderate. We demonstrate the merits of our approach in an extensive simulation study and apply the model to US macroeconomic data to evaluate its forecasting capabilities.
On the geoarchaeology of Limyra (SW Anatolia)—new insights into the famous Lycian city and its environs
Authors: Stock Friederike , Seyer Martin , Symanczyk Anika , Uncu Levent , Brückner Helmut 
Published: March 2020

AbstractGeoarchives in ancient settlement sites and their environs bear valuable information about Holocene landscape evolution and human–environment interactions. During the last six millennia, sea‐level and coastline changes have had a significant impact on coastal settlements, some of which even had to be relocated. This paper reveals new insights into the spatio‐temporal development of the Lycian city of Limyra. Selected sediment cores were analyzed using a multiproxy approach, combining sedimentology, geochemistry, micropaleontology, and 14C dating. When the postglacial sea‐level rise decelerated, a coastal barrier and a deep lake, presumably a lagoon, evolved after the mid‐Holocene. The siltation history of the lake is complex: three coastal peat layers (mid‐4th millennium BC, end of 3rd/beginning of 2nd millennium BC, beginning of 1st millennium BC), indicate periods of semiterrestrial conditions. That they are sandwiched by lake sediments is consistent with new expansion phases of the lake, most likely triggered by coseismic subsidence. There is evidence of a former lakeshore, dated to between 1400 and 1100 BC, with an intentionally deposited layer of anthropogenic remains, now at 5.5 m below the surface. In the mid‐1st millennium BC, the lake silted up, river channels evolved, and people started to settle the area of the later city of Limyra.
Epigenetic regulation of oligodendrocyte differentiation: From development to demyelinating disorders
Authors: Samudyata  , Castelo‐Branco Gonçalo , Liu Jia 
Published: March 2020

AbstractThe maintenance of progenitor states or the differentiation of progenitors into specific lineages requires epigenetic remodeling of the gene expression program. In the central nervous system, oligodendrocyte progenitors (OPCs) give rise to oligodendrocytes (OLs), whose main function has been thought to be to produce myelin, a lipid‐rich structure insulating the axons. However, recent findings suggest diverse OL transcriptional states, which might imply additional functions. The differentiation of OPCs into postmitotic OLs is a highly regulated and sensitive process and requires temporal waves of gene expression through epigenetic remodeling of the genome. In this review, we will discuss recent advances in understanding the events shaping the chromatin landscape through histone modifications and long noncoding RNAs during OPC differentiation, in physiological and pathological conditions. We suggest that epigenetic regulation plays a fundamental role in governing the accessibility of transcriptional machinery to DNA sequences, which ultimately determines functional outcomes in OLs.
One‐pot porogen free method fabricated porous microsphere‐aggregated 3D PCL scaffolds for bone tissue engineering
Authors: Yao Qingqing , Liu Yu , Pan Yining , Miszuk Jacob M. , Sun Hongli 
Published: March 2020

AbstractThree‐dimensional (3D) scaffolds with interconnected, hierarchically structured pores, and biomimetic nanostructures are desirable for tissue engineering, where preparation with a facile and biocompatible strategy remains challenging. In the present work, an innovative porous microspheres‐aggregated 3D PCL scaffold with macropores, micropores, and nanofibrous‐like structures was fabricated through a one‐pot thermally induced phase separation (TIPS) method without the use of any porogen or specific instruments. Importantly, the porosity, pore size, and mechanical properties of our scaffolds were tailorable through tuning of the polymer concentration. Interestingly, the bioactivity of our 3D PCL scaffolds was significantly improved, as abundant apatite‐like layers were formed on the 3D porous scaffolds, while no obvious apatite was observed on the 2D flat PCL film. Moreover, the high surface area attributed to the hierarchical macro/micro/nanostructure enabled our 3D porous scaffold to serve as a drug delivery depot for sustained release of both small molecule drug (phenamil) and protein (BMP2). In addition to sustained drug release, the hierarchical structure and high mechanical properties also contribute to significantly improving BMP2‐induced osteogenic differentiation. In summary, we developed a novel PCL porous scaffold through a facile, one‐pot TIPS method and demonstrated its promising potential application in large bone defect repair.
Fabrication and cellular interactions of nanoporous tantalum oxide
Authors: Uslu Ece , Öztatlı Hayriye , Garipcan Bora , Ercan Batur 
Published: March 2020

AbstractTantalum possesses remarkable chemical and mechanical properties, and thus it is considered to be one of the next generation implant materials. However, the biological properties of tantalum remain to be improved for its use in tissue engineering applications. To enhance its cellular interactions, implants made of tantalum could be modified to obtain nanofeatured surfaces via the electrochemical anodization process. In this study, anodization parameters were adjusted to obtain a nanoporous surface morphology on tantalum surfaces and systematically altered to control the pore sizes from 25 to 65 nm using an aqueous HF:H2SO4 electrolyte. Results indicated the formation of Ta2O5‐based nanoporous surface layers, which had up to 28% more surface area and increased nanophase roughness (more than twofolds) compared to nonporous tantalum upon the anodization. It was observed that the nanoporous tantalum oxide surfaces promoted nearly 25% more fibroblast proliferation at 5 days in vitro and 15.5% more cellular spreading. Thus, nanoporous tantalum oxide surfaces can be used to increase biological interactions of the cells and provide a means of improving bioactivity of tantalum for biomaterial applications.
Automation of Harboe method for the measurement of plasma free hemoglobin
Authors: Chung Hee‐Jung , Chung Jae‐Woo , Yi Joowon , Hur Mina , Lee Tae Hwan , Hwang Sang‐Hyun , Song Yoon Kyung , Lee Do Hoon 
Published: March 2020

AbstractBackgroundAlthough plasma free hemoglobin (fHb) test is important for assessing intravascular hemolysis, it is still dependent on the gold standard Harboe method using manual and labor‐intensive spectrometric measurements at the wavelength of 380‐415‐450 nm. We established an automated fHb assay using a routine chemistry autoanalyzer that can be tuned to a wavelength of 380‐416‐450 nm.MethodsThe linearity, precision, accuracy, correlation, and sample carryover of fHb measurement using TBA200FRneo method and manual Harboe method were evaluated, respectively. fHb values measured by manual Harboe method were compared with those measured by our new automated TBA200FRneo method.ResultsfHb measurements were linear in the range of 0.05~38.75 µmol/L by TBA200FRneo and 0.05~9.69 µmol/L by manual Harboe method. Imprecision analysis (%CV) revealed 0.9~2.8% for TBA200FRneo method and 5.3~13.6% for the manual Harboe method. Comparison analysis showed 0.9986 of correlation coefficient (TBA200FRneo = 0.970 × Harboe + 0.12). In analytical accuracy analysis, the manual Harboe method revealed about 4 times higher average total error % (12.2%) than the TBA200FRneo automated method (2.8%). The sample carryover was −0.0016% in TBA200FRneo method and 0.0038% in Harboe method.ConclusionsIn the measurement of fHb, the automated TBA200FRneo method showed better performance than the conventional Harboe method. It is expected that the automated fHb assay using the routine chemistry analyzer can replace the gold standard Harboe method which is labor‐intensive and need an independent spectrophotometry equipment.
Editorial for “Texture Analysis of High b‐value Diffusion‐Weighted Imaging for Evaluating Consistency of Pituitary Macroadenomas”
Authors: van Staalduinen Eric K. , Bangiyev Lev 
Published: March 2020

Level of Evidence5Technical EfficacyStage 3J. Magn. Reson. Imaging 2020;51:1514–1515.
Adjuvant therapy following resection of gastroenteropancreatic neuroendocrine tumors provides no recurrence or survival benefit
Authors: Barrett James R. , Rendell Victoria , Pokrzywa Courtney , Lopez‐Aguiar Alexandra G. , Cannon John , Poultsides George A. , Rocha Flavio , Crown Angelena , Beal Eliza , Michael Pawlik Timothy , Fields Ryan , Panni Roheena Z. , Smith Paula , Idrees Kamran , Cho Clifford , Beems Megan , Maithel Shishir , Weber Sharon , Erik Abbott Daniel 
Published: March 2020

AbstractBackground and ObjectivesLack of high‐level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non‐standard of care use.MethodsPatients with primary GEP NETs who underwent curative‐intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence‐free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts.ResultsIn resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five‐year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P < .01). RFS with somatostatin analog therapy (compared to none) was lower (P < .01), as was OS (P = .01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor‐specific characteristics (RFS P < .01).ConclusionsOur data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high‐risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.