bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action
Authors: Wong Yin Kwan , Xu Chengchao , Kalesh Karunakaran A. , He Yingke , Lin Qingsong , Wong W. S. Fred , Shen Han‐Ming , Wang Jigang 
Published: June 2017

AbstractArtemisinin and its derivatives (collectively termed as artemisinins) are among the most important and effective antimalarial drugs, with proven safety and efficacy in clinical use. Beyond their antimalarial effects, artemisinins have also been shown to possess selective anticancer properties, demonstrating cytotoxic effects against a wide range of cancer types both in vitro and in vivo. These effects appear to be mediated by artemisinin‐induced changes in multiple signaling pathways, interfering simultaneously with multiple hallmarks of cancer. Great strides have been taken to characterize these pathways and to reveal their anticancer mechanisms of action of artemisinin. Moreover, encouraging data have also been obtained from a limited number of clinical trials to support their anticancer property. However, there are several key gaps in knowledge that continue to serve as significant barriers to the repurposing of artemisinins as effective anticancer agents. This review focuses on important and emerging aspects of this field, highlighting breakthroughs in unresolved questions as well as novel techniques and approaches that have been taken in recent studies. We discuss the mechanism of artemisinin activation in cancer, novel and significant findings with regards to artemisinin target proteins and pathways, new understandings in artemisinin‐induced cell death mechanisms, as well as the practical issues of repurposing artemisinin. We believe these will be important topics in realizing the potential of artemisinin and its derivatives as safe and potent anticancer agents.
Tumor angiogenesis revisited: Regulators and clinical implications
Authors: Ronca Roberto , Benkheil Mohammed , Mitola Stefania , Struyf Sofie , Liekens Sandra 
Published: June 2017

AbstractSince Judah Folkman hypothesized in 1971 that angiogenesis is required for solid tumor growth, numerous studies have been conducted to unravel the angiogenesis process, analyze its role in primary tumor growth, metastasis and angiogenic diseases, and to develop inhibitors of proangiogenic factors. These studies have led in 2004 to the approval of the first antiangiogenic agent (bevacizumab, a humanized antibody targeting vascular endothelial growth factor) for the treatment of patients with metastatic colorectal cancer. This approval launched great expectations for the use of antiangiogenic therapy for malignant diseases. However, these expectations have not been met and, as knowledge of blood vessel formation accumulates, many of the original paradigms no longer hold. Therefore, the regulators and clinical implications of angiogenesis need to be revisited. In this review, we discuss recently identified angiogenesis mediators and pathways, new concepts that have emerged over the past 10 years, tumor resistance and toxicity associated with the use of currently available antiangiogenic treatment and potentially new targets and/or approaches for malignant and nonmalignant neovascular diseases.
Randomized feasibility trial to improve hydroxyurea adherence in youth ages 10–18 years through community health workers: The HABIT study
Authors: Green Nancy S. , Manwani Deepa , Matos Sergio , Hicks April , Soto Luisa , Castillo Yina , Ireland Karen , Stennett Yvonne , Findley Sally , Jia Haomiao , Smaldone Arlene 
Published: June 2017

AbstractIntroductionThe main therapeutic intervention for sickle cell disease (SCD) is hydroxyurea (HU). The effect of HU is largely through dose‐dependent induction of fetal hemoglobin (HbF). Poor HU adherence is common among adolescents.MethodsOur 6‐month, two‐site pilot intervention trial, “HABIT,” was led by culturally aligned community health workers (CHWs). CHWs performed support primarily through home visits, augmented by tailored text message reminders. Dyads of youth with SCD ages 10–18 years and a parent were enrolled. A customized HbF biomarker, the percentage decrease from each patients’ highest historical HU‐induced HbF, “Personal best,” was used to qualify for enrollment and assess HU adherence. Two primary outcomes were as follows: (1) intervention feasibility and acceptability and (2) HU adherence measured in three ways: monthly percentage improvement toward HbF Personal best, proportion of days covered (PDC) by HU, and self‐report.ResultsTwenty‐eight dyads were enrolled, of which 89% were retained. Feasibility and acceptability were excellent. Controlling for group assignment and month of intervention, the intervention group improved percentage decrease from Personal best by 2.3% per month during months 0–4 (P = 0.30), with similar improvement in adherence demonstrated using pharmacy records. Self‐reported adherence did not correlate. Dyads viewed CHWs as supportive for learning about SCD and HU, living with SCD and making progress in coordinated self‐management responsibility to support a daily HU habit. Most parents and youth appreciated text message HU reminders.ConclusionsThe HABIT pilot intervention demonstrated feasibility and acceptability with promising effect toward improved medication adherence. Testing in a larger multisite intervention trial is warranted.
The natural history of fetal diagnosed isolated ventricular septal defect
Authors: Cho Young‐Sun , Park So Eun , Hong Soo‐Kyung , Jeong Na‐Yeong , Choi Eun‐Young 
Published: June 2017

AbstractObjectiveThis study was undertaken to clarify the natural course of ventricular septal defect, and to find an index that would help in prenatal counseling.MethodsBetween January 2010 and December 2014, 18 188 fetuses underwent echocardiographic examinations. Of these, 228 isolated ventricular septal defect cases were retrospectively reviewed.ResultsIn this retrospective study, the incidence of isolated ventricular septal defect was 1.25% (228/18 188). There were 146 patients who underwent echocardiography after delivery in order to confirm the natural course of patients with isolated ventricular septal defect. Of the 146 cases, 64 cases (43.84%) had the ventricular septal defect naturally closed in the fetal period. Of the 82 patients with ventricular septal defect at birth, 25 patients showed natural closure during follow‐up. However, four patients (2.74%) required surgical treatment for ventricular septal defect. In case of perimembranous defects, natural closure is more frequent in the fetal period than in the postnatal period.ConclusionOur results indicate that 60.96% (89/146) of isolated ventricular septal defects diagnosed during the fetal life are closed naturally. Perimembranous type defect, small defect (<2 mm) and maternal age less than 35 years are the good prognostic factors for the natural closure during fetal life. © 2017 John Wiley & Sons, Ltd.
Solar cell efficiency tables (version 50)
Authors: Green Martin A. , Hishikawa Yoshihiro , Warta Wilhelm , Dunlop Ewan D. , Levi Dean H. , Hohl‐Ebinger Jochen , Ho‐Baillie Anita W.H. 
Published: June 2017

AbstractConsolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules are presented. Guidelines for inclusion of results into these tables are outlined, and new entries since January 2017 are reviewed.
Can the propensity of protein crystallization be increased by using systematic screening with metals?
Authors: Hegde Raghurama P. , Pavithra Gowribidanur C. , Dey Debayan , Almo Steven C. , Ramakumar S. , Ramagopal Udupi A. 
Published: June 2017

AbstractProtein crystallization is one of the major bottlenecks in protein structure elucidation with new strategies being constantly developed to improve the chances of crystallization. Generally, well‐ordered epitopes possessing complementary surface and capable of producing stable inter‐protein interactions generate a regular three‐dimensional arrangement of protein molecules which eventually results in a crystal lattice. Metals, when used for crystallization, with their various coordination numbers and geometries, can generate such epitopes mediating protein oligomerization and/or establish crystal contacts. Some examples of metal‐mediated oligomerization and crystallization together with our experience on metal‐mediated crystallization of a putative rRNA methyltransferase from Sinorhizobium meliloti are presented. Analysis of crystal structures from protein data bank (PDB) using a non‐redundant data set with a 90% identity cutoff, reveals that around 67% of proteins contain at least one metal ion, with ∼14% containing combination of metal ions. Interestingly, metal containing conditions in most commercially available and popular crystallization kits generally contain only a single metal ion, with combinations of metals only in a very few conditions. Based on the results presented in this review, it appears that the crystallization screens need expansion with systematic screening of metal ions that could be crucial for stabilizing the protein structure or for establishing crystal contact and thereby aiding protein crystallization.
A QM/MM study of the catalytic mechanism of SAM methyltransferase RlmN from Escherichia coli
Authors: Zhao Chenxiao , Dong Lihua , Liu Yongjun 
Published: June 2017

AbstractRlmN is a radical S‐adenosylmethionine (SAM) enzyme that catalyzes the C2 methylation of adenosine 2503 (A2503) in 23S rRNA and adenosine 37 (A37) in several Escherichia coli transfer RNAs (tRNA). The catalytic reaction of RlmN is distinctly different from that of typical SAM‐dependent methyltransferases that employs an SN2 mechanism, but follows a ping‐pong mechanism which involves the intermediate methylation of a conserved cysteine residue. Recently, the x‐ray structure of a key intermediate in the RlmN reaction has been reported, allowing us to perform combined quantum mechanics and molecular mechanics (QM/MM) calculations to delineate the reaction details of RlmN at atomic level. Starting from the Cross‐Linked RlmN C118A−tRNA complex, the possible mechanisms for both the formation and the resolution of the cross‐linked species (IM2) have been illuminated. On the basis of our calculations, IM2 is formed by the attack of the C355‐based methylene radical on the sp2‐hybridized C2 of the adenosine ring, corresponding to energy barrier of 14.4 kcal/mol, and the resolution of IM2 is confirmed to follow a radical fragmentation mechanism. The cleavage of C′–S′ bond of mC355‐A37 cross‐link is in concert with the deprotonation of C2 by C118 residue, which is the rate‐limiting step with an energy barrier of 17.4 kcal/mol. Moreover, the cleavage of C′–S′ bond of IM2 can occur independently, that is, it does not require the loss of an electron of IM2 and the formation of disulfide bond between C355 and C118 as precondition. These findings would deepen the understanding of the catalysis of RlmN.
One‐pot Synthesis of Novel Composite@Composite‐Typed Core@Shell Nanostructures and the Adsorption Property for Dye Wastewater
Authors: Yang Liming , Teng Yiran , Teng Fei 
Published: June 2017

AbstractIn this work, the novel composite@composite‐type core@shell nanostructures, i.e. Na0.5Ce0.5MoO4‐MoS2@Na0.5Ce0.5MoO4‐MoS2, have been synthesized via one‐pot hydrothermal method. The core and shell are both composed of Na0.5Ce0.5MoO4‐MoS2 but with different mass ratios of Na0.5Ce0.5MoO4 to MoS2, which are obviously different from the commonly reported core@shell nanostructures with the single‐component core and the single‐component shell. Besides, it is found that for single dye solution, 20 wt% core@shell sample has an significantly improved adsorption capability for rhodamine B (RhB), but a poor adsorption capability for methyl orange (MO) dye. In RhB‐MO mixture solution, the adsorption of RhB has been greatly promoted by MO. In addition, Cr(VI) ion has significantly decreased the adsorption capacity of RhB; meanwhile, K(I) ion can slightly promote MO adsorption. This work provides a simple preparation approach to the new composite‐type core@shell nanostructures, and can help us to understand the adsorption processes for practical wastewaters.
Antiproliferative Effects against A549, Hep3B and FL Cell Lines of Cyclotriphosphazene‐Based Novel Protic Molten Salts: Spectroscopic, Crystallographic and Thermal Results.
Authors: Okumuş Aytuğ , Akbaş Hüseyin , Karadağ Ahmet , Aydın Ali , Kılıç Zeynel , Hökelek Tuncer 
Published: June 2017

AbstractThe protic molten salts (PMOS) of (1 a‐ 6 b) have been prepared from the reactions of tetrapyrrolidino (1‐3) and tetrapiperidino (4‐6) fully substituted phosphazenes with the gentisic and γ‐resorcylic acids. The structures of PMOS (1 a‐6 b) were characterized by elemental analyses, FTIR and 1H, 13C{1H}, 31P{1H} NMR techniques. The crystal structures of 1 b and 2 b were established by X‐ray diffraction method. The thermal properties of PMOS were verified using thermogravimetric instruments. In addition, this study also focused on the pharmacological abilities of the PMOS to affect the cell growth and cell cytotoxicity on A549, Hep3B and normal human amnion (FL) cell lines and to interact with calf thymus DNA (CT‐DNA). Studies on the cells displayed that these PMOS demonstrated significant antiproliferative effect in conjunction with caused apoptotic‐like changes in morphology. The PMOS are able to strongly bind to CT‐DNA through minor groove binding modes with hyperchromic effect. The IC50 and binding constant ranges of the PMOS were found to be as 25–160 μM and 0.5 x 103 −12.0 x 103 M−1, respectively. These findings indicate that the PMOS 1 b‐6 b are more antiproliferative than those of the PMOS 1 a‐6 a. Moreover, it is observed that the CT‐DNA most significantly bound the PMOS 1 b‐6 b. Consequently, a good correlation between the antiproliferative effects and their binding activities of these PMOS was observed.
Relationships between social support and student burnout: A meta‐analytic approach
Authors: Kim Boram , Jee Sooin , Lee Joungwha , An Sunghee , Lee Sang Min 
Published: June 2017

AbstractThis study is a meta‐analysis of 19 relevant studies, with 95,434 participants, investigating the relationships between various types of social support and 3 dimensions of student burnout. The overall results indicate that social support is negatively correlated with student burnout. Specifically, school or teacher supports have the strongest negative relationship to student burnout. Social supports from parents and from peers also have a significant negative relationship with student burnout. Among the 3 dimensions of student burnout, inefficacy was more strongly related to social support than emotional exhaustion or cynicism. The results of a moderation analysis suggest that the type of schools (secondary school and postsecondary school) affected the relationships between the overall social support and student burnout. We discuss the implications to ameliorate student burnout.
An Addressable 2D Heterogeneous Nanoreactor to Study the Enzyme‐Catalyzed Reaction at the Interface
Authors: Wang Dianming , Zhang Guoliang , Zhang Yiyang , Xin Ling , Dong Yuanchen , Liu Yang , Liu Dongsheng 
Published: June 2017

AbstractMembrane plays significant role in cellular enzymatic reactions. To better understand its function on membrane integral or bound enzymes, DNA origami and frame‐guided assembly strategy are combined to construct a given‐size, addressable enzyme‐containing nanomembrane as a heterogeneous reactor to explore the enzymatic catalyst reaction on the membrane. The enzymes in the membrane are located precisely. This new kind of membrane can enrich hydrophobic substrate molecules in aqueous solution to the embedded enzymes. Otherwise, this nanomembrane shows the capability of substrate selectivity, which plays important role in the highly efficient and specific properties of enzymes in vivo.
Water flow, ecological dynamics, and management in the lower Limpopo Valley: a long‐term view
Authors: Ekblom A. , Gillson L. , Notelid M. 
Published: June 2017

In this contribution, we review long‐term (millennial–decadal scale) river‐flow changes, climate interactions, and interlinkage with vegetation dynamics, as well as society and policy, focusing on the lower Limpopo Valley (from the South African border through Mozambique). Drawing on paleoecological data, we address the valley's potential for defining critical ecological thresholds and managing an adaptive ecological landscape, by focusing on the dynamic relationship between different drivers (fire, hydrology, and grass/tree relationships). We briefly review the long‐term interactions between water flow, climate variability, and society using archeological records and written sources. Lastly, we analyze the social and political context of water management, focusing on the last 100 years and transboundary water management. We also discuss planning and mitigation in relation to climate change and rainfall extremes that are projected to increase. It is stressed that forward‐thinking policies must heed long‐term climate variability, hydrology and biological and social impact and to plan and mitigate for environmental events. The discussion also brings to the fore the importance of an adaptable and equitable strategy in cross‐border water sharing. WIREs Water 2017, 4:e1228. doi: 10.1002/wat2.1228This article is categorized under:

Engineering Water > Planning Water
Water and Life > Stresses and Pressures on Ecosystems
Science of Water > Water and Environmental Change
Stable–streamlined and helical cavities following the impact of Leidenfrost spheres
Authors: Mansoor M. M. , Vakarelski I. U. , Marston J. O. , Truscott T. T. , Thoroddsen S. T. 
Published: June 2017

We report results from an experimental study on the formation of stable–streamlined and helical cavity wakes following the free-surface impact of Leidenfrost spheres. Similar to the observations of Mansoor et al. (J. Fluid Mech., vol. 743, 2014, pp. 295–326), we show that acoustic ripples form along the interface of elongated cavities entrained in the presence of wall effects as soon as the primary cavity pinch-off takes place. The crests of these ripples can act as favourable points for closure, producing multiple acoustic pinch-offs, which are found to occur in an acoustic pinch-off cascade. We show that these ripples pacify with time in the absence of physical contact between the sphere and the liquid, leading to extremely smooth cavity wake profiles. More importantly, the downward-facing jet at the apex of the cavity is continually suppressed due to a skin-friction drag effect at the colliding cavity-wall junction, which ultimately produces a stable–streamlined cavity wake. This streamlined configuration is found to experience drag coefficients an order of a magnitude lower than those acting on room-temperature spheres. A striking observation is the formation of helical cavities which occur for impact Reynolds numbers $Re_{0}\gtrsim 1.4\times 10^{5}$ and are characterized by multiple interfacial ridges, stemming from and rotating synchronously about an evident contact line around the sphere equator. The contact line is shown to result from the degeneration of Kelvin–Helmholtz billows into turbulence which are observed forming along the liquid–vapour interface around the bottom hemisphere of the sphere. Using sphere trajectory measurements, we show that this helical cavity wake configuration has 40 %–55 % smaller force coefficients than those obtained in the formation of stable cavity wakes.
Constitutional War Initiation and the Obama Presidency
Authors: Ramsey Michael D. 
Published: June 2017

In 2007, presidential candidate Barack Obama argued that the U.S. president did not have independent constitutional authority to use military force except in response to an actual or imminent attack on the United States. Since 2008, President Obama has directed the use of U.S. military force in at least seven countries (Iraq, Syria, Libya, Yemen, Afghanistan, Pakistan, and Somalia). Critics find inconsistency in these positions, contending that the Obama presidency will be remembered for expansion of the presidency's war powers. But when the administration's record is closely examined, these claims seem overstated. At least with regard to war initiation, the Obama presidency need not be regarded as materially enhancing the president's constitutional powers.This assessment begins by establishing two baselines. First, most war powers scholars agree that under the Constitution's original meaning, Congress’ power to “declare War” required the president to seek congressional approval prior to initiating war. This constitutional command had substantial grey areas, including responses to threats and attacks, relations with non-state actors, and low-level hostilities. Nonetheless, the basic proposition stated by candidate Obama appears well founded both in the Constitution's text itself and in early postratification practice. Second, in the modern (post-Vietnam War) era, most scholars agree that the practice has changed somewhat, with presidents asserting an expanded independent authority over uses of military force. This essay agrees with that description, although it contends that the change in actual practice is less dramatic than commentary sometimes claims.
Upper Jurassic travertine at El Macanudo, Argentine Patagonia: a fossil geothermal field modified by hydrothermal silicification and acid overprinting
Authors: GUIDO DIEGO M. , CAMPBELL KATHLEEN A. 
Published: June 2017

AbstractThe Deseado Massif hosts numerous Late Jurassic (150 Ma) fossil geothermal systems related to an extensive volcanic event developed in a diffuse extensional back-arc setting. Detailed mapping, petrography and mineralogical observations of El Macanudo outcrops verify that it represents a hot-spring-related travertine partially replaced by silica and delineated by six sedimentary facies. These are large concentric cones (F1), laminated vertical columnar structures (F2), porous layers (F3), shrubby and irregular lamination (F4), low-amplitude wavy bedding (F5) and mounds and breccias (F6). The Macanudo Norte Outcrop rocks constitute a silica-replaced travertine sequence, with development of large conical stromatolites in a deep pool or geothermally influenced shallow lacustrine environment, surrounded by a subaerial travertine apron terrace; whereas, the Macanudo Sur Outcrop is a subaerial travertine mound sequence. Structurally controlled vent areas occur in both northern (F1) and southern (F6) outcrops, mainly located along regional NNE- and ENE-trending faults. The other sedimentary units display a concentric distribution of travertine facies with respect to the interpreted vent areas. The El Macanudo palaeo-hot spring deposit is situated in an eroded Jurassic volcanic centre, and records a complex evolutionary-fluid history. The sediments archived three different Jurassic events, when large and long-lasting hydrothermal systems were active across the region. This relative temporal sequence was formed by: (1) travertine precipitation; (2) development of a silica cap, where early silicification was responsible for exceptional preservation of some stromatolitic fabrics; and (3) acid alteration, recorded by dissolution textures and clay formation, and caused by a palaeo-phreatic water-level drop.