bluuebunny/crossref_metadata_2025_split huggingface dataset:
MEK inhibitors overcome resistance to BET inhibition across a number of solid and hematologic cancers
Authors: Wyce Anastasia , Matteo Jeanne J. , Foley Shawn W. , Felitsky Daniel J. , Rajapurkar Satyajit R. , Zhang Xi-Ping , Musso Melissa C. , Korenchuk Susan , Karpinich Natalie O. , Keenan Kathryn M. , Stern Melissa , Mathew Lijoy K. , McHugh Charles F. , McCabe Michael T. , Tummino Peter J. , Kruger Ryan G. , Carpenter Christopher , Barbash Olena 
Published: April 2018

AbstractBET inhibitors exhibit broad activity in cancer models, making predictive biomarkers challenging to define. Here we investigate the biomarkers of activity of the clinical BET inhibitor GSK525762 (I-BET; I-BET762) across cancer cell lines and demonstrate that KRAS mutations are novel resistance biomarkers. This finding led us to combine BET with RAS pathway inhibition using MEK inhibitors to overcome resistance, which resulted in synergistic effects on growth and survival in RAS pathway mutant models as well as a subset of cell lines lacking RAS pathway mutations. GSK525762 treatment up-regulated p-ERK1/2 levels in both RAS pathway wild-type and mutant cell lines, suggesting that MEK/ERK pathway activation may also be a mechanism of adaptive BET inhibitor resistance. Importantly, gene expression studies demonstrated that the BET/MEK combination uniquely sustains down-regulation of genes associated with mitosis, leading to prolonged growth arrest that is not observed with either single agent therapy. These studies highlight a potential to enhance the clinical benefit of BET and MEK inhibitors and provide a strong rationale for clinical evaluation of BET/MEK combination therapies in cancer.
Crystalline polymer nanofibers with ultra-high strength and thermal conductivity
Authors: Shrestha Ramesh , Li Pengfei , Chatterjee Bikramjit , Zheng Teng , Wu Xufei , Liu Zeyu , Luo Tengfei , Choi Sukwon , Hippalgaonkar Kedar , de Boer Maarten P. , Shen Sheng 
Published: April 2018

AbstractPolymers are widely used in daily life, but exhibit low strength and low thermal conductivity as compared to most structural materials. In this work, we develop crystalline polymer nanofibers that exhibit a superb combination of ultra-high strength (11 GPa) and thermal conductivity, exceeding any existing soft materials. Specifically, we demonstrate unique low-dimensionality phonon physics for thermal transport in the nanofibers by measuring their thermal conductivity in a broad temperature range from 20 to 320 K, where the thermal conductivity increases with increasing temperature following an unusual ~T1 trend below 100 K and eventually peaks around 130–150 K reaching a metal-like value of 90 W m−1 K−1, and then decays as 1/T. The polymer nanofibers are purely electrically insulating and bio-compatible. Combined with their remarkable lightweight-thermal-mechanical concurrent functionality, unique applications in electronics and biology emerge.
Aqueous rechargeable zinc/sodium vanadate batteries with enhanced performance from simultaneous insertion of dual carriers
Authors: Wan Fang , Zhang Linlin , Dai Xi , Wang Xinyu , Niu Zhiqiang , Chen Jun 
Published: April 2018

AbstractRechargeable aqueous zinc-ion batteries are promising energy storage devices due to their high safety and low cost. However, they remain in their infancy because of the limited choice of positive electrodes with high capacity and satisfactory cycling performance. Furthermore, their energy storage mechanisms are not well established yet. Here we report a highly reversible zinc/sodium vanadate system, where sodium vanadate hydrate nanobelts serve as positive electrode and zinc sulfate aqueous solution with sodium sulfate additive is used as electrolyte. Different from conventional energy release/storage in zinc-ion batteries with only zinc-ion insertion/extraction, zinc/sodium vanadate hydrate batteries possess a simultaneous proton, and zinc-ion insertion/extraction process that is mainly responsible for their excellent performance, such as a high reversible capacity of 380 mAh g–1 and capacity retention of 82% over 1000 cycles. Moreover, the quasi-solid-state zinc/sodium vanadate hydrate battery is also a good candidate for flexible energy storage device.
Polaron freezing and the quantum liquid-crystal phase in the ferromagnetic metallic La0.67Ca0.33MnO3
Authors: Panopoulos Nikolaos , Pissas Michael , Kim Hae Jin , Kim Jin-Gyu , Yoo Seung Jo , Hassan Jamal , AlWahedi Yasser , Alhassan Saeed , Fardis Michael , Boukos Nikos , Papavassiliou Georgios 
Published: April 2018

AbstractThe remarkable electronic properties of colossal magnetoresistive manganites are widely believed to be caused by the competition between a ferromagnetic metallic state and an antiferromagnetic insulating state with complex spin, charge, and orbital ordering. However, the physics underlying their magnetotransport properties is still not clear, especially the role of correlated Jahn–Teller polarons, which depending on temperature and doping, might form a liquid, glass or stripe polaron state. This question touches one of the most fundamental problems in the physics of doped Mott insulators, i.e. understanding the mechanism that chemical doping makes an insulator becoming superconductive as in the case of cuprates, or exhibiting the colossal magnetoresistance effect, as in the case of manganites. Here, by using 139La NMR and high resolution transmission electron microscopy in the temperature range 3.2–1000 K, we have monitored the formation and evolution of CE-type polarons in optimally doped La0.67Ca0.33MnO3. While NMR experiments show that correlated polarons dominate electron spin dynamics in the ferromagnetic phase, at very low temperatures they appear to form a quantum liquid-crystal like ferromagnetic phase, embedded into a ferromagnetic matrix with 3D polaron correlations. This is evidence that similarly to high Tc cuprates, quantum soft phases underlie the exotic physical properties of colossal magnetoresistive manganites.
Enhancing learning and retrieval of new information: a review of the forward testing effect
Authors: Yang Chunliang , Potts Rosalind , Shanks David R. 
Published: April 2018

AbstractIn recent years evidence has accumulated showing that interim testing of studied information facilitates learning and retrieval of new information—the forward testing effect. In the current article, we review the empirical evidence and putative mechanisms underlying this effect. The possible negative effects of administering interim tests and how these negative effects can be mitigated are discussed. We also propose some important directions for future research to explore. Finally, we summarize the practical implications for optimizing learning and teaching in educational settings.
miR-9 upregulation leads to inhibition of erythropoiesis by repressing FoxO3
Authors: Zhang Yunyuan , Li Liping , Yu Chunjie , Senyuk Vitalyi , Li Fuxing , Quigley John G. , Zhu Tongyu , Qian Zhijian 
Published: April 2018

AbstractMicroRNAs (miRNAs) are emerging as critical regulators of normal and malignant hematopoiesis. In previous studies of acute myeloid leukemia miR-9 overexpression was commonly observed. Here, we show that ectopic expression of miR-9 in vitro and in vivo significantly blocks differentiation of erythroid progenitor cells with an increase in reactive oxygen species (ROS) production. Consistent with this observation, ROS scavenging enzymes, including superoxide dismutase (Sod2), Catalase (Cat), and glutathine peroxidase (Gpx1), are down-regulated by miR-9. In addition, miR-9 suppresses expression of the erythroid transcriptional regulator FoxO3, and its down-stream targets Btg1 and Cited 2 in erythroid progenitor cells, while expression of a constitutively active form of FoxO3 (FoxO3-3A) reverses miR-9-induced suppression of erythroid differentiation, and inhibits miR-9-induced ROS production. Thus, our findings indicate that aberrant expression of miR-9 blocks erythropoiesis by deregulating FoxO3-mediated pathways, which may contribute to the ineffective erythropoiesis observed in patients with hematological malignancies.
Molecular design of radiocopper-labelled Affibody molecules
Authors: Tolmachev Vladimir , Grönroos Tove J. , Yim Cheng-Bin , Garousi Javad , Yue Ying , Grimm Sebastian , Rajander Johan , Perols Anna , Haaparanta-Solin Merja , Solin Olof , Ferdani Riccardo , Orlova Anna , Anderson Carolyn J. , Karlström Amelie Eriksson 
Published: April 2018

AbstractThe use of long-lived positron emitters 64Cu or 61Cu for labelling of Affibody molecules may improve breast cancer patients’ stratification for HER-targeted therapy. Previous animal studies have shown that the use of triaza chelators for 64Cu labelling of synthetic Affibody molecules is suboptimal. In this study, we tested a hypothesis that the use of cross-bridged chelator, CB-TE2A, in combination with Gly-Glu-Glu-Glu spacer for labelling of Affibody molecules with radiocopper would improve imaging contrast. CB-TE2A was coupled to the N-terminus of synthetic Affibody molecules extended either with a glycine (designation CB-TE2A-G-ZHER2:342) or Gly-Glu-Glu-Glu spacer (CB-TE2A-GEEE-ZHER2:342). Biodistribution and targeting properties of 64Cu-CB-TE2A-G-ZHER2:342 and 64Cu-CB-TE2A-GEEE-ZHER2:342 were compared in tumor-bearing mice with the properties of 64Cu-NODAGA-ZHER2:S1, which had the best targeting properties in the previous study. 64Cu-CB-TE2A-GEEE-ZHER2:342 provided appreciably lower uptake in normal tissues and higher tumor-to-organ ratios than 64Cu-CB-TE2A-G-ZHER2:342 and 64Cu-NODAGA-ZHER2:S1. The most pronounced was a several-fold difference in the hepatic uptake. At the optimal time point, 6 h after injection, the tumor uptake of 64Cu-CB-TE2A-GEEE-ZHER2:342 was 16 ± 6%ID/g and tumor-to-blood ratio was 181 ± 52. In conclusion, a combination of the cross-bridged CB-TE2A chelator and Gly-Glu-Glu-Glu spacer is preferable for radiocopper labelling of Affibody molecules and, possibly, other scaffold proteins having high renal re-absorption.
A wheat caffeic acid 3-O-methyltransferase TaCOMT-3D positively contributes to both resistance to sharp eyespot disease and stem mechanical strength
Authors: Wang Minxia , Zhu Xiuliang , Wang Ke , Lu Chungui , Luo Meiying , Shan Tianlei , Zhang Zengyan 
Published: April 2018

AbstractPlant caffeic acid 3-O-methyltransferase (COMT) has been implicated in the lignin biosynthetic pathway through catalyzing the multi-step methylation reactions of hydroxylated monomeric lignin precursors. However, genetic evidence for its function in plant disease resistance is poor. Sharp eyespot, caused primarily by the necrotrophic fungus Rhizoctonia cerealis, is a destructive disease in hexaploid wheat (Triticum aestivum L.). In this study, a wheat COMT gene TaCOMT-3D, is identified to be in response to R. cerealis infection through microarray-based comparative transcriptomics. The TaCOMT-3D gene is localized in the long arm of the chromosome 3D. The transcriptional level of TaCOMT-3D is higher in sharp eyespot-resistant wheat lines than in susceptible wheat lines, and is significantly elevated after R. cerealis inoculation. After R. cerealis inoculation and disease scoring, TaCOMT-3D-silenced wheat plants exhibit greater susceptibility to sharp eyespot compared to unsilenced wheat plants, whereas overexpression of TaCOMT-3D enhances resistance of the transgenic wheat lines to sharp eyespot. Moreover, overexpression of TaCOMT-3D enhances the stem mechanical strength, and lignin (particular syringyl monolignol) accumulation in the transgenic wheat lines. These results suggest that TaCOMT-3D positively contributes to both wheat resistance against sharp eyespot and stem mechanical strength possibly through promoting lignin (especially syringyl monolignol) accumulation.
Low field magneto-tunable photocurrent in CoFe2O4 nanostructure films for enhanced photoelectrochemical properties
Authors: Singh Simrjit , Khare Neeraj 
Published: April 2018

AbstractEfficient solar to hydrogen conversion using photoelectrochemical (PEC) process requires semiconducting photoelectrodes with advanced functionalities, while exhibiting high optical absorption and charge transport properties. Herein, we demonstrate magneto-tunable photocurrent in CoFe2O4 nanostructure film under low applied magnetic fields for efficient PEC properties. Photocurrent is enhanced from ~1.55 mA/cm2 to ~3.47 mA/cm2 upon the application of external magnetic field of 600 Oe leading to ~123% enhancement. This enhancement in the photocurrent is attributed to the reduction of optical bandgap and increase in the depletion width at CoFe2O4/electrolyte interface resulting in an enhanced generation and separation of the photoexcited charge carriers. The reduction of optical bandgap in the presence of magnetic field is correlated to the shifting of Co2+ ions from octahedral to tetrahedral sites which is supported by the Raman spectroscopy results. Electrochemical impedance spectroscopy results confirm a decrease in the charge transfer resistance at the CoFe2O4/electrolyte interface in the presence of magnetic field. This work evidences a coupling of photoexcitation properties with magnetic properties of a ferromagnetic-semiconductor and the effect can be termed as magnetophototronic effect.
A new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli
Authors: Velasco Elsa , Wang Suning , Sanet Marianna , Fernández-Vázquez Jorge , Jové Daniel , Glaría Estibaliz , Valledor Annabel F. , O’Halloran Thomas V. , Balsalobre Carlos 
Published: April 2018

AbstractMetal limitation is a common situation during infection and can have profound effects on the pathogen’s success. In this report, we examine the role of zinc limitation in the expression of a virulence factor in uropathogenic Escherichia coli. The pyelonephritis isolate J96 carries two hlyCABD operons that encode the RTX toxin α-hemolysin. While the coding regions of both operons are largely conserved, the upstream sequences, including the promoters, are unrelated. We show here that the two hlyCABD operons are differently regulated. The hly
II
operon is efficiently silenced in the presence of zinc and highly expressed when zinc is limited. In contrast, the hly
I
operon does not respond to zinc limitation. Genetic studies reveal that zinc-responsive regulation of the hly
II
operon is controlled by the Zur metalloregulatory protein. A Zur binding site was identified in the promoter sequence of the hly
II
operon, and we observe direct binding of Zur to this promoter region. Moreover, we find that Zur regulation of the hly
II
operon modulates the ability of E. coli J96 to induce a cytotoxic response in host cell lines in culture. Our report constitutes the first description of the involvement of the zinc-sensing protein Zur in directly modulating the expression of a virulence factor in bacteria.
Disentangling flows in the solar transition region
Authors: Zacharias P. , Hansteen V. H. , Leenaarts J. , Carlsson M. , Gudiksen B. V. 
Published: April 2018

Context. The measured average velocities in solar and stellar spectral lines formed at transition region temperatures have been difficult to interpret. The dominant redshifts observed in the lower transition region naturally leads to the question of how the upper layers of the solar (and stellar) atmosphere can be maintained. Likewise, no ready explanation has been made for the average blueshifts often found in upper transition region lines. However, realistic three-dimensional radiation magnetohydrodynamics (3D rMHD) models of the solar atmosphere are able to reproduce the observed dominant line shifts and may thus hold the key to resolve these issues. Aims. These new 3D rMHD simulations aim to shed light on how mass flows between the chromosphere and corona and on how the coronal mass is maintained. These simulations give new insights into the coupling of various atmospheric layers and the origin of Doppler shifts in the solar transition region and corona.
Methods. The passive tracer particles, so-called corks, allow the tracking of parcels of plasma over time and thus the study of changes in plasma temperature and velocity not only locally, but also in a co-moving frame. By following the trajectories of the corks, we can investigate mass and energy flows and understand the composition of the observed velocities.
Results. Our findings show that most of the transition region mass is cooling. The preponderance of transition region redshifts in the model can be explained by the higher percentage of downflowing mass in the lower and middle transition region. The average upflows in the upper transition region can be explained by a combination of both stronger upflows than downflows and a higher percentage of upflowing mass. The most common combination at lower and middle transition region temperatures are corks that are cooling and traveling downward. For these corks, a strong correlation between the pressure gradient along the magnetic field line and the velocity along the magnetic field line has been observed, indicating a formation mechanism that is related to downward propagating pressure disturbances. Corks at upper transition region temperatures are subject to a rather slow and highly variable but continuous heating process.
Conclusions. Corks are shown to be an essential tool in 3D rMHD models in order to study mass and energy flows. We have shown that most transition region plasma is cooling after having been heated slowly to upper transition region temperatures several minutes before. Downward propagating pressure disturbances are identified as one of the main mechanisms responsible for the observed redshifts at transition region temperatures.
Verwirrspiel um den Ginseng
Authors: Häringer Erwin 
Published: April 2018

ZusammenfassungGinseng wird bereits seit mehr als 2000 Jahren angebaut, kultiviert und in der naturheilkundlichen Behandlung erfolgreich verwendet. In Herstellung und Bedeutung
zu unterscheiden ist der weiße vom roten Ginseng. So enthält z. B. das Konzentrat aus weißem Ginseng doppelt so viel der für die Wirksamkeit wichtigen
Ginsenoside wie das aus rotem Ginseng. Die Regulierungsbehörden in Europa erkennen Ginseng bislang nur als traditionelles Mittel an, in Fernost ist die
Verwendung von Ginseng hingegen etabliert. Zusammen mit weiteren ordnungstherapeutischen Maßnahmen und der naturheilkundlichen Anwendung der adaptogenen Pflanze
ist mit Ginseng ein bewährter, integrativer Ansatz in der Therapie der Fatigue und des Chronischen Fatigue Syndroms möglich.
Erschöpfungssyndrome mit Āyurveda behandeln
Authors: Chopra Ananda Samir 
Published: April 2018

ZusammenfassungErschöpfungssyndrome, insbesondere wenn sie lange andauern, betreffen den Menschen meist auf allen Ebenen seines Seins und sind mit erheblichem Leiden verbunden. Aus Sicht der Āyurveda-Medizin besteht bei solchen tiefgreifenden Erschöpfungszuständen eine Aggravation des Vāta. Die individuelle Ausprägung der Symptome wird allerdings bedingt durch das Zusammentreffen von Imbalance und individueller Konstitution. Ein multimodaler Behandlungsansatz aus diätetischen Maßnahmen, pflanzlichen Arzneien und gegebenenfalls intensiver Pañcakarma-Therapie, der individuell geplant und durchgeführt werden muss, erweist sich hier als besonders wirksam.
Zu welchen Themen suchen Angehörige von Demenzbetroffenen telefonische oder emailbasierte Beratung auf? Aktuelle Ergebnisse des bundesweiten Beratungsangebots der Deutschen Alzheimer Gesellschaft e.V.
Authors: Pendergrass Anna , Weiß Saskia , Gräßel Elmar 
Published: April 2018

Zusammenfassung
Hintergrund Seit 15 Jahren existiert das Alzheimer – Telefon der Deutschen Alzheimer Gesellschaft e.V. (DAlzG) als bundesweites psychosoziales Beratungsangebot und hat sich als wichtige Säule bei der Unterstützung von Menschen mit Demenz und ihren Familien etabliert. Folgende Ziele der vorliegenden Untersuchung waren zu evaluieren: a) warum Angehörige, die einen Demenzbetroffenen pflegen oder unterstützen, telefonische Beratung in Anspruch nehmen, b) ob diese Beratung einmalig stattfindet oder eine langfristige Begleitung der Angehörigen darstellt und c) ob sich die telefonischen von den email-basierten Anfragen bezüglich der Thematiken unterscheiden.
Studiendesign und Methode Die Daten beruhen auf den Anfragen von 3744 Angehörigen, die sich im Jahr 2015 an die DAlzG gewandt haben. Es wurden soziodemografische Daten der Angehörigen und der Demenzbetroffenen, die Themen und die Charakteristika des Telefonats sowie die Emailanfragen thematisch erfasst.
Ergebnisse Die Anrufer waren zu 70,3% weiblich, hauptsächlich die (Schwieger-) Kinder der Betroffenen (59,9%) und lebten mit den Demenzbetroffenen zusammen (49,7%). Über 2 Drittel der Anrufer (70%) suchten Unterstützung bezüglich der Schwierigkeiten im Umgang mit dem Erkrankten (z. B. wegen herausfordernden Verhaltensweisen) und 36,5% der Angehörigen suchten weiterführende Hilfen. An dritter Stelle standen rechtliche und finanzielle Themen im Fokus (23,5%). Es fanden zu 92,2% einmalige Beratungen statt. Die Beratungsanliegen der Angehörigen, die per Email Kontakt aufnahmen, unterschieden sich nicht maßgeblich von den Beratungsthemen der telefonischen Beratung.
Schlussfolgerung Bei vielen Themen besteht Bedarf nach weiterführender Beratung „vor Ort“. Ärzte und andere Akteure im Gesundheitswesen sollten daher eine aktive Beratungseinstellung gegenüber Angehörigen von Demenzbetroffenen einnehmen.
Antisuicidal Effects in Mood Disorders: Are They Unique to Lithium?
Authors: Tondo Leonardo , Baldessarini Ross 
Published: April 2018

Abstract
Introduction Suicidal behavior is strongly associated with depression in major depressive (MDD) and bipolar (BD) disorders, especially with associated behavioral activation, dysphoria, or agitation. A rare intervention with evidence of suicide risk-reducing as well as mood-stabilizing effects in mood disorder patients is lithium.
Methods We reviewed available research evidence on associations of long-term treatment with lithium with risk of suicidal behavior. We meta-analyzed 12 randomized trials in 10 reports (with at least 1 suicide in either treatment arm) including both BD and MDD subjects, with particular attention to comparisons of lithium with placebo or other pharmacological treatments. We also summarized ecological studies on lithium concentration in local drinking water and reported suicide rates.
Results We found substantial reduction of risks of suicide and attempts with long-term lithium treatment, particularly in depressive phases of BD and in MDD. Risk of suicidal behavior was higher in mixed (agitated-dysphoric) states than in manic or hypomanic periods. Risk of suicide fatality, specifically, was lower with lithium than with placebo and probably with mood-altering anticonvulsants or antidepressants.
Discussion Long-term treatment with lithium has growing evidence of suicide- and attempt-sparing effects, probably greater than with anticonvulsants or antidepressants; antipsychotics remain to be tested adequately. However, the ethical and scientifically adequate design and conduct of trials of treatments aimed at suicide prevention remain challenging and underdeveloped.