bluuebunny/crossref_metadata_2025 huggingface dataset:
Light‐Induced Spin Transitions in Copper‐Nitroxide‐Based Switchable Molecular Magnets: Insights from Periodic DFT+U Calculations
Authors: Sánchez‐de‐Armas Rocío , Cruz Hernández Norge , Calzado Carmen J.
Published: September 2018

The electronic structure and magnetic interactions of three members of the breathing crystal Cu(hfac)2LR family (hfac=hexafluoroacetylacetonato, LR=pyrazole‐substituted nitronyl nitroxides with R=Me, Et, Pr, iPr, Bu ), mainly Cu(hfac)2LPr (1), Cu(hfac)2LBu⋅0.5 C8H18 (2) and Cu(hfac)2LBu⋅0.5 C8H10 (3), have been analyzed by means of periodic plane‐wave based DFT+U calculations. These CuII‐nitroxide based molecular magnets display thermally and optically induced switchable behavior and light‐induced excited spin state trapping phenomena. The calculations confirm the presence of temperature‐dependent exchange interaction within the spin triads formed by the nitroxide‐copper(II)‐nitroxide units, in line with the changes observed in the effective magnetic moment. Moreover, they quantify the interchain interaction mediated by the terminal nitroxide group of two spin triads in neighboring polymer chains. This interaction competes with the exchange interaction within the spin triads at high temperature, and introduces 1D exchange channels that do not coincide with the polymeric chains. The density of states reveal that the low‐lying conduction states potentially involved in the UV/Vis transitions are located on the nitroxide radicals, the hfac groups and the Cu atoms. Then, the density of states is almost independent of the solvent and the R group. This suggests the possibility of light‐induced spin switching for other members of this family. The 500 nm band of the low‐temperature phase can be ascribed to a ligand‐to‐metal charge transfer transition between the nitroxide and Cu bands.
Modular Enzymatic Cascade Synthesis of Vitamin B5 and Its Derivatives
Authors: Abidin Mohammad Z. , Saravanan Thangavelu , Zhang Jielin , Tepper Pieter G. , Strauss Erick , Poelarends Gerrit J.
Published: September 2018

Access to vitamin B5 [(R)‐pantothenic acid] and both diastereoisomers of α‐methyl‐substituted vitamin B5 [(R)‐ and (S)‐3‐((R)‐2,4‐dihydroxy‐3,3‐dimethylbutanamido)‐2‐methylpropanoic acid] was achieved using a modular three‐step biocatalytic cascade involving 3‐methylaspartate ammonia lyase (MAL), aspartate‐α‐decarboxylase (ADC), β‐methylaspartate‐α‐decarboxylase (CrpG) or glutamate decarboxylase (GAD), and pantothenate synthetase (PS) enzymes. Starting from simple non‐chiral dicarboxylic acids (either fumaric acid or mesaconic acid), vitamin B5 and both diastereoisomers of α‐methyl‐substituted vitamin B5, which are valuable precursors for promising antimicrobials against Plasmodium falciparum and multidrug‐resistant Staphylococcus aureus, can be generated in good yields (up to 70 %) and excellent enantiopurity (>99 % ee). This newly developed cascade process may be tailored and used for the biocatalytic production of various vitamin B5 derivatives by modifying the pantoyl or β‐alanine moiety.
Single‐Site, Organometallic Aluminum Catalysts for the Precise Group Transfer Polymerization of Michael‐Type Monomers
Authors: Weger Michael , Giuman Marco M. , Knaus Maximilian G. , Ackermann Maximilian , Drees Markus , Hornung Julius , Altmann Philipp J. , Fischer Roland A. , Rieger Bernhard
Published: September 2018

Invited for the cover of this issue is the group of Bernhard Rieger and colleagues at the Technical University of Munich. The image depicts a polymerization process with an aluminum‐based catalyst and its cyclopentadienyl‐ligands. Read the full text of the article at 10.1002/chem.201802075.
Cobalt‐Based Metal–Organic Framework Nanoarrays as Bifunctional Oxygen Electrocatalysts for Rechargeable Zn‐Air Batteries
Authors: Chen Guangbo , Zhang Jian , Wang Faxing , Wang Lanlan , Liao Zhongquan , Zschech Ehrenfried , Müllen Klaus , Feng Xinliang
Published: September 2018

Owing to their high theoretical energy density, environmental benign character, and low cost, rechargeable Zn‐air batteries have emerged as an attractive energy technology. Unfortunately, their energy efficiency is seriously plagued by sluggish oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) that alternately occurs on air electrodes. Herein, we demonstrate Co‐based metal–organic framework (Co(bpdc)(H2O)4 (bpdc=biphenyl −4, 4′‐dicarboxylic acid), Co‐MOF) arrays as novel bifunctional oxygen electrocatalysts. The Co‐MOF is in situ constructed on a three‐dimensional graphite foam (GF) through a hydrothermal reaction. In a 1 m KOH aqueous solution, the resultant Co‐MOF/GF exhibits an OER overpotential of only ≈220 mV at 10 mA cm−2, which is much lower than those for Ir/C and previously reported noble metal‐free electrocatalysts. In conjunction with its ORR half‐wave potential of 0.7 V (vs. RHE), the Co‐MOF/GF manifests a greatly decreased potential gap of ≈0.75 V in comparison with Pt/C‐Ir/C couple and previously reported bifunctional oxygen electrocatalysts. Furthermore, an assembled rechargeable zinc‐air battery using Co‐MOF electrocatalyst in an air electrode delivers a maximum power density of 86.2 mW cm−2 and superior charge–discharge performance. Microscopic, spectroscopic and electrochemical analyses prove that the initial Co‐MOF is transformed into Co‐oxyhydroxides during the OER and ORR process, which essentially serve as bifunctional active centers.
Box‐Behnken response surface modeling assisted enantiomeric resolution of some racemic β‐blockers using HPTLC and β‐cyclodextrin as chiral mobile phase additive: Application to check the enantiomeric purity of betaxolol
Authors: El‐Kimary Eman I. , Ragab Marwa A.A.
Published: September 2018

Stereospecific separation method of (±) betaxolol, (±) carvedilol, and (±) sotalol using High Performance Thin Layer Chromatography (HPTLC) and β‐cyclodextrin as chiral selector has been developed and validated. The Box‐Behnken surface response design was selected for optimizing the operating variables based on 15 trials design. The optimized method involves separation on Fluka HPTLC silica gel plates 60 F254 (20 × 10 cm) using acetonitrile‐methanol‐acetic acid‐water (3.4:3.6:0.18:1 v/v) as a mobile phase containing 0.57 mM β‐cyclodextrin. Densitometric measurements were made at 220 nm for betaxolol and sotalol or at 245 nm for carvedilol. Maximum separation of the enantiomers of the three drugs was obtained by optimizing concentration of chiral selector, the mobile phase composition including acetonitrile amount in the organic part of the mobile phase and the volume of acetic acid added. The proposed method enables estimation of (−) and (+) enantiomers of betaxolol in drug substance and in various pharmaceuticals. The detection limit of betaxolol was 0.15 and 0.13 μg band−1 for (−) and (+) enantiomers, respectively. The detection limits were found to be 0.2 and 0.3 μg band−1 for carvedilol and sotalol, respectively, as racemate. In addition, the proposed method was applied in checking the enantiomeric purity of (−) BET in the presence of (+) BET at 1% level where the inactive (+) enantiomer was quantified with good accuracy and precision at 1% level in the active (−) enantiomer.
Lithiumgewinnung aus heimischen Rohstoffen
Authors: Martin Gunther , Schneider Anke , Bertau Martin
Published: September 2018

Lithium gilt als eines der strategischen Elemente mit einem großen Zukunftspotential. Vor dem Hintergrund eines steigenden Bedarfs, aber auch der Ungleichverteilung der weltweiten Lithiumvorkommen gilt es, auch heimische Vorkommen wie die Zinnwalditlagerstätte bei Zinnwald/Cínovec (650.000 t Li), für eine mögliche großtechnische Lithiumgewinnung genauer zu betrachten. Unter Berücksichtigung der besonderen Voraussetzungen des lithiumhaltigen Minerals erfolgte die Entwicklung von zwei verschiedenen Verfahren zur Lithiumcarbonatgewinnung aus Zinnwalditkonzentrat. Dabei wurden sowohl ein ganzheitlicher Salzsäureaufschluss wie auch ein selektives Direktcarbonatisierungsverfahren mittels überkritischem Kohlendioxid untersucht. Bei dem salzsäurebasierten Verfahren wird durch eine optimierte Laugung bis zu 96 % des im Zinnwalditkonzentrat enthaltenen Lithiums mobilisiert. Säurerückgewinnungsverfahren reduzieren dabei den Säurebedarf. Die Umsetzung von kalziniertem Zinnwalditkonzentrat (~ 950 °C) im System sc‐CO2/H2O ist ein vielversprechender Ansatz zur Lithiumcarbonatgewinnung (COOL‐Verfahren). Grundlage des Direktcarbonatisierungsverfahren ist das umfassende Verständnis der mineralischen Zusammensetzung sowie des thermischen Verhaltens in oxidierender Atmosphäre. Bei minimalem Chemikalieneinsatz werden durch den CO2‐Aufschluss hochselektiv Alkalimetallkationen, bevorzugt Lithium, als Hydrogencarbonate mobilisiert. Die aus ökonomischer Sicht zu bevorzugenden Aufschlussparameter (Doppellaugung, Fest : Flüssig‐Verhältnis ~ 1:30, 230 °C, 100 bar, 3 h, d50 ~ 18 μm) führten zu einer Lithiumlaugungsrate von 71 %.
Cationic Branched Polyethylenimine (BPEI) Disables Antibiotic Resistance in Methicillin‐Resistant Staphylococcus epidermidis (MRSE)
Authors: Lam Anh K. , Hill Melissa A. , Moen Erika L. , Pusavat Jennifer , Wouters Cassandra L. , Rice Charles V.
Published: September 2018

Staphylococcus epidermidis is one of the most prevalent prokaryotic species on human skin and mucosal membranes that constitute the commensal flora. S. epidermidis has become one of the most common causes of primary bacteremia. Infections are difficult to diagnose because the pathogen has natural niches on human skin and the ability to adhere to inanimate surfaces via biofilms. Alarmingly, S. epidermidis has acquired resistance to many antibiotics, which presents a danger to human health. Known as methicillin‐resistant S. epidermidis (MRSE), most clinical isolates of MRSE in North America exhibit β‐lactam resistance primarily due to the presence of mecA, a gene that bestows β‐lactam antibiotic resistance in a manner similar to methicillin‐resistant Staphylococcus aureus (MRSA). MecA encodes for expression of penicillin‐binding protein 2a (PBP2a), which is absent in β‐lactam susceptible strains of S. epidermidis. We can disable this resistance factor in MRSE with 600‐Da branched polyethylenimine (BPEI). Cationic BPEI targets anionic wall teichoic acid (WTA), an essential cofactor for proper functioning of PBP2a. We found that BPEI synergizes the activity of β‐lactam antibiotics against MRSE. Growth curves suggest that the combination of BPEI and oxacillin is bactericidal. Electron micrographs indicate abnormalities in the cellular septa and cell walls of treated samples. Therefore, first‐line clinical treatments can be effective against MRSE when used in combination with BPEI.
Castration remains despite decreasing definitive treatment of localized prostate cancer in the elderly: A case for de‐implementation
Authors: Skolarus Ted A. , Caram Megan EV , Chapman Christina H. , Smith David C. , Hollenbeck Brent K. , Hawley Sarah , Tsodikov Alexander , Sales Anne , Wittmann Daniela , Zaslavsky Alexander
Published: September 2018

Maximizing the quality and quantity of life among men with localized prostate cancer who are elderly and have competing comorbidities may be achieved more effectively, either by treating these patients definitively or by opting for observation rather than using primary androgen‐deprivation therapy. A better understanding of the optimal ways to de‐implement this low‐value cancer care appears to be warranted for both elderly patients, who have little to gain by it, and younger patients, who have more to lose by foregoing definitive treatment with surgery or radiation therapy.
Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR‐mutant non–small cell lung cancer: Multicenter, single‐arm, phase 2 trial (ABC Study)
Authors: Hata Akito , Katakami Nobuyuki , Kaji Reiko , Yokoyama Toshihide , Kaneda Toshihiko , Tamiya Motohiro , Inoue Takako , Kimura Hiromi , Yano Yukihiro , Tamura Daisuke , Morita Satoshi , Negoro Shunichi , the HANSHIN Oncology Group for
Published: September 2018

BACKGROUND

Preclinical studies suggested that the addition of bevacizumab could overcome acquired resistance (AR) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the clinical efficacy and safety of a combination of afatinib and bevacizumab after AR.

METHODS

Patients with EGFR‐mutant non–small cell lung cancer after AR were enrolled during any line of therapy. Afatinib was prescribed at 30 mg, and 15 mg/kg bevacizumab was administered every 3 weeks until progression.

RESULTS

Between October 2014 and May 2017, 32 eligible patients were evaluated. The mutation subtypes were Del‐19 (20 [63%]), L858R (11 [34%]), and L861Q (1 [3%]). T790M was detected in 14 patients (44%). The median number of prior regimens was 4 (range, 1‐10). Six patients obtained a partial response, and 23 had stable disease; this resulted in an objective response rate (ORR) of 18.8% (95% confidence interval [CI], 7.2%‐36.4%) and a disease control rate of 90.7% (95% CI, 75.0%‐98.0%). The median progression‐free survival (PFS) was 6.3 months (95% CI, 3.9‐8.7 months). The ORRs and median PFS times of T790M+ and T790M− patients were 14.3% and 22.2%, respectively, and 6.3 and 7.1 months, respectively; those of Del‐19 and L858R patients were 20.0% and 11.1%, respectively, and 6.3 and 5.1 months, respectively. Grade 3 or higher adverse events (incidence ≥ 10%) included paronychia (25%), hypertension (41%), and proteinuria (19%). There were no treatment‐related deaths, interstitial lung disease, or bevacizumab‐associated severe bleeding.

CONCLUSIONS

Afatinib plus bevacizumab demonstrated clinical efficacy and safety after AR to EGFR TKIs and could be a therapeutic salvage option for T790M− populations.
Toward colour rendering method of window glass
Authors: Arbab Shabnam , Matusiak Barbara Szybinska
Published: September 2018

The aim of this study was to expand the understanding of modern glazing materials' effects on the colour distortion in interiors and to develop a rather simple colour rendering method useful for any type of glazing and based on colorimetry measurements and mathematical calculations. The qualitative and quantitative aspects of different light sources on colour rendering are frequently discussed topics among the researchers, but one of the issues touched only sporadically is the impact of tinted glazing on colour rendering of daylight. The study started from the following question: Is the colour rendering method proposed by Lynes reliable also for present‐day high‐tech glazing types? The experiment was carried out in the Norwegian University of Science and Technology's (NTNU) with the artificial sky, which enables mimicking of skylight of the following correlated colour temperatures: 2700 K, 6500 K and 8000 K. Three high‐tech glazing types were used in five different transmittance scenarios. Colorimetric measurements were taken with the SpectraScan PR655 spectroradiometer. The findings indicated that the Lynes method is reliable to predict which glazing have the biggest impact on all aspects of colour but only in 6500 K. New set of measures have been proposed: average colour shift distance for hue gamut area for Chroma and median transmittance for Value. However, for higher precision regarding the direction of shift and the overall perception of the respective colours in building context, experiments with subjects are needed.
Hidden Dicarbene Nature of Acetylenes and Captodative Bonding on Carbon
Authors: Bijina Padinjare Veetil , Suresh Cherumuttathu H.
Published: September 2018

The density functional theory derived molecular electrostatic potential (MESP), 13C NMR chemical shift (δ), bond order, and coordination reactions show that alkynes (RCCR) attain 1,2‐dicarbene nature during CCR angle bending. Alkyne carbon atoms of bent structures exhibit MESP features unique to lone‐pair bearing atoms, δ around 200 ppm typical for carbene centers and large reduction in CC triple bond character. Lone pair bearing atoms of R substituents enhance the carbene character. The bent alkynes can be trapped with Lewis acids (BH3, BF3, AlF3 and AlCl3) as the lone pairs developed on carbon centers provide strong donor type dative bonding. The dative bond gives a formal valence electron count six on carbon and suggests the for‐mation of acceptor type dative bonding to carbon from Lewis base (NH3). Reaction of alkynes with (Lewis acid)←(Lewis base) systems yield (Lewis acid)2←(Alkyne)←(Lewis base)2 complexes which are exothermic and exergonic for many cases. These complexes are examples of captodative carbon(II) compounds.
Predation‐mediated ecosystem services and disservices in agricultural landscapes
Authors: Tschumi Matthias , Ekroos Johan , Hjort Cecilia , Smith Henrik G. , Birkhofer Klaus
Published: September 2018

Ecological intensification may reduce environmental externalities of agriculture by harnessing biodiversity to benefit regulating ecosystem services. However, to propose management options for the production of such services, there is a need to understand the spatiotemporal dynamics of net effects between ecosystem services and disservices provided by wild organisms across taxonomic groups in relation to habitat and landscape management. We studied the contribution of predatory vertebrates and invertebrates (including both carnivores and seed herbivores) to regulating ecosystem services and disservices in 16 cereal fields in response to a local habitat contrast and a landscape complexity gradient. From May to November 2016, we provided weed (predation reflects an ecosystem service) and crop (predation reflects a disservice) seeds, as well as pest (predation reflects an ecosystem service) and beneficial (predation reflects a disservice) invertebrate prey to predators. Seed predation was dominated by vertebrates, while vertebrates and invertebrates contributed equally to predation of animal prey. Before harvest, predation steadily increased from very low levels in May to high levels in July independent of the resource type. After harvest, ecosystem services declined more rapidly than disservices. The presence of adjacent seminatural grasslands promoted crop seed predation, but reduced pest prey predation. Predation on beneficial prey decreased with increasing proportions of seminatural grassland in the landscape. Predatory vertebrates and invertebrates provide important ecosystem services due to the consumption of pests. However, beneficial invertebrates and crop seeds were often consumed to a similar or even higher extent than harmful invertebrates or weed seeds. Our results therefore raise concerns that management options aimed at enhancing service providers may simultaneously increase levels of disservices. By considering positive and negative effects simultaneously, this study addresses an important knowledge gap and highlights the importance of interactions between local management, landscape composition, and service and disservice provision across taxa and over time. Considering trade‐offs between ecosystem services and disservices when evaluating the net effects of biodiversity conservation measures on ecosystem service provision is crucial. Future agri‐environment schemes that offer payments for seminatural habitats may need to provide higher compensation for farmers in cases where net effects are likely to be negative.
Complex mathematical analysis of photobioreactor system
Authors: Scheufele Fabiano Bisinella , Hinterholz Camila Larissa , Zaharieva Maya M. , Najdenski Hristo M. , Módenes Aparecido Nivaldo , Trigueros Daniela Estelita Goes , Borba Carlos Eduardo , Espinoza‐Quiñones Fernando Rodolfo , Kroumov Alexander Dimitrov
Published: September 2018

Modeling as a tool solves extremely difficult tasks in life sciences. Recently, schemes of culturing of microalgae have received special attention because of its unique features and possible uses in many industrial applications for renewable energy production and high value products isolation. The goal of this review is to present the use of system analysis theory applied to microalgae culturing modeling and process development. The review mainly focuses on the modeling of the key steps of autotrophic growth under the integral biorefinery concept of the microalgae biomass. The system approach follows systematically a procedure showing the difficulties by modeling of sub‐systems. The development of microalgae kinetics and computational fluid dynamics (CFD) studies were analyzed in details as sub‐systems in advanced design of photobioreactor (PBR). This review logically follows the trends of the modeling procedure and clarifies how this approach may save time and money during the research efforts. The result of this work is a successful development of a complex PBR mathematical analysis in the frame of the integral biorefinery concept.
The Small Sellers of Program Evaluation Services in the United States
Authors: Hwalek Melanie A. , Straub Victoria L.
Published: September 2018

This chapter attempts to deepen the understanding of small sellers of evaluation services through a survey of the American Evaluation Association's Independent Consulting Topical Interest Group members, delving into the inner workings of their organizations. The chapter examines where boutique evaluators in the United States generate their revenues, how some have survived as independent evaluators for 10 or more years, how they differentiate themselves from their competition, whether they do subcontract work with large sellers, and how they deliver high‐quality evaluation services. A case example of one small seller, SPEC Associates, is used to elucidate the survey findings.
The Big Evaluation Enterprises in the United States
Authors: Peck Laura R.
Published: September 2018

This issue of New Directions for Evaluation addresses the market for evaluation, where demand and supply intersect to generate knowledge relevant to decisions for policy‐making and program practice. Lemire et al. (this issue) elaborated on the U.S. federal evaluation market. This chapter examines the “big evaluation enterprises” within that market.
The combined effects of yogurt and exercise in healthy adults: Implications for biomarkers of depression and cardiovascular diseases
Authors: Kim Hyun‐Kyung , Kim Soo‐Hwan , Jang Chul‐Soo , Kim Sung‐In , Kweon Chang‐Oh , Kim Byung‐Won , Ryu Jae‐Ki
Published: September 2018

Several studies have reported individual benefits of yogurt and exercise on health; however, their combined effects remain unclear. Twenty‐four healthy individuals participated in the study and were randomly assigned to the following four groups: control, yogurt, exercise, and combination. The participants consumed yogurt and exercised for 2 weeks, and we examined the combined effects of yogurt and exercise on physiological biomarkers. Individually, yogurt and exercise did not exert a significant effect on biomarkers of depression or cardiovascular disease, although vitamin D levels increased in the exercise group. However, in the combination group, serotonin levels increased, while levels of triglycerides and high‐sensitivity C‐reactive protein, which are biomarkers for cardiovascular diseases, decreased. In conclusion, the results of the study showed that, in healthy individuals, a combination of yogurt and exercise led to greater increases in serotonin levels and reductions in triglyceride and high‐sensitivity C‐reactive protein levels, relative to those observed for yogurt or exercise alone; therefore, this combination could have implications for the prevention of depression and cardiovascular disease.
Great Expectations: Principal Investigator and Trainee Perspectives on Hiring, Supervision, and Mentoring
Authors: Kaps Leonard , Stine Jonathan G. , Mellinger Jessica , Vilarinho Silvia
Published: September 2018

A functioning mentor–trainee relationship is of high importance in academia. Discrepancies in expectations between principal investigators (PIs) and trainees are a source of misunderstandings and conflicts, endangering scientific progress and career advancement. In this pilot study, we sought to explore the expectations of PIs and trainees, providing consensus data from physician‐scientists and junior researchers who attended an educational workshop, entitled “The EASL/AASLD Masterclass,” in December 2017. Twenty‐three Masterclass attendees, comprising nine trainees (four Ph.D. candidates, five postdoctoral researchers) and 14 PIs, responded to an online survey. Both parties were asked to score 29 predefined statements of important expectations, enabling a comparative analysis for each statement between the groups. For the trainees, the success of the PI, either mirrored by successful mentoring or scientific work, as well as a clear road for academic development are of utmost importance. PIs did not prioritize these aspects, highlighting discrepancies of expectations. PIs prioritized trainee competence, reliability, and strong daily initiative/work ethic, qualities that were also recognized to be important by the trainee group but not to same degree as PIs. Conclusion:Discrepancies in expectations pose a preventable threat to the mentor–trainee relationship if considered and discussed beforehand. The discrepancy in the most common expectations between the two groups could have resulted from the fact that trainees prioritize outcomes of success while PIs focus on the necessary qualities leading to those outcomes.
Systematic variation in evapotranspiration trends and drivers across the Northeastern United States
Authors: Vadeboncoeur Matthew A. , Green Mark B. , Asbjornsen Heidi , Campbell John L. , Adams Mary Beth , Boyer Elizabeth W. , Burns Douglas A. , Fernandez Ivan J. , Mitchell Myron J. , Shanley James B.
Published: September 2018

The direction and magnitude of responses of evapotranspiration (ET) to climate change are important to understand, as ET represents a major water and energy flux from terrestrial ecosystems, with consequences that feed back to the climate system. We inferred multidecadal trends in water balance in 11 river basins (1940–2012) and eight smaller watersheds (with records ranging from 18 to 61 years in length) in the Northeastern United States. Trends in river basin actual ET (AET) varied across the region, with an apparent latitudinal pattern: AET increased in the cooler northern part of the region (Maine) but decreased in some warmer regions to the southwest (Pennsylvania–Ohio). Of the four small watersheds with records longer than 45 years, two fit this geographic pattern in AET trends. The differential effects of the warming climate on AET across the region may indicate different mechanisms of change in more‐ vs. less‐energy‐limited watersheds, even though annual precipitation greatly exceeds potential ET across the entire region. Correlations between AET and time series of temperature and precipitation also indicate differences in limiting factors for AET across the Northeastern U.S. climate gradient. At many sites across the climate gradient, water‐year AET correlated with summer precipitation, implying that water limitation is at least transiently important in some years, whereas correlations with temperature indices were more prominent in northern than southern sites within the region.
Aberrant expression of SETD1A promotes survival and migration of estrogen receptor α‐positive breast cancer cells
Authors: Jin Ming Li , Kim Young Woong , Jin Hong Lan , Kang Hoin , Lee Eun Kyung , Stallcup Michael R. , Jeong Kwang Won
Published: September 2018

The histone H3 lysine 4‐specific methyltransferase SETD1A is associated with transcription activation and is considered a key epigenetic regulator that modulates the cell cycle and metastasis in triple‐negative breast cancer cells. However, the clinical role of SETD1A in estrogen receptor (ER)‐positive breast cancer cells remains unclear. Here, we examined whether SETD1A is a potential target for ERα‐positive breast cancer therapy. SETD1A expression was upregulated in breast tumor tissue compared to that in normal breast tissue. Moreover, ER‐target genes regulated by SETD1A were particularly enriched in cell cycle and cancer pathways. SETD1A is involved in histone H3K4 methylation, subsequent recruitment of ERα, and the establishment of accessible chromatin structure at the enhancer region of ERα target genes. In addition to ERα target genes, other cell survival genes were also downregulated by SETD1A depletion in MCF‐7 cells, leading to significant decrease in cell proliferation and migration, and spontaneous induction of apoptosis. We also found that miR‐1915‐3p functioned as a novel regulator of SETD1A expression in breast cells. Importantly, the growth of tamoxifen‐resistant MCF‐7 cells was effectively repressed by SETD1A knockdown. These results indicate that SETD1A may serve as a molecular target and prognostic indicator in ERα‐positive breast cancer.
Circulating insulin‐like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition
Authors: Bradbury Kathryn E. , Appleby Paul N. , Tipper Sarah J. , Travis Ruth C. , Allen Naomi E. , Kvaskoff Marina , Overvad Kim , Tjønneland Anne , Halkjær Jytte , Cervenka Iris , Mahamat‐Saleh Yahya , Bonnet Fabrice , Kaaks Rudolf , Fortner Renée T. , Boeing Heiner , Trichopoulou Antonia , La Vecchia Carlo , Stratigos Alexander J. , Palli Domenico , Grioni Sara , Matullo Giuseppe , Panico Salvatore , Tumino Rosario , Peeters Petra H. , Bueno‐de‐Mesquita H. Bas , Ghiasvand Reza , Veierød Marit B. , Weiderpass Elisabete , Bonet Catalina , Molina Elena , Huerta José M. , Larrañaga Nerea , Barricarte Aurelio , Merino Susana , Isaksson Karolin , Stocks Tanja , Ljuslinder Ingrid , Hemmingsson Oskar , Wareham Nick , Khaw Kay‐Tee , Gunter Marc J. , Rinaldi Sabina , Tsilidis Konstantinos K. , Aune Dagfinn , Riboli Elio , Key Timothy J.
Published: September 2018

Insulin‐like growth factor‐I (IGF‐I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF‐I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF‐I concentrations and melanoma risk. A nested case–control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF‐I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF‐I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF‐I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF‐I measured in adulthood and the risk of melanoma.
The addition of pretreatment plasma Epstein–Barr virus DNA into the eighth edition of nasopharyngeal cancer TNM stage classification
Authors: Lee Victor Ho‐Fun , Kwong Dora Lai‐Wan , Leung To‐Wai , Choi Cheuk‐Wai , O'Sullivan Brian , Lam Ka‐On , Lai Vincent , Khong Pek‐Lan , Chan Sik‐Kwan , Ng Chor‐Yi , Tong Chi‐Chung , Ho Patty Pui‐Ying , Chan Wing‐Lok , Wong Lai‐San , Leung Dennis Kwok‐Chuen , Chan Sum‐Yin , So Tsz‐Him , Luk Mai‐Yee , Lee Anne Wing‐Mui
Published: September 2018

The eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal carcinoma (NPC) was launched. It remains unknown if incorporation of nonanatomic factors into the stage classification would better predict survival. We prospectively recruited 518 patients with nonmetastatic NPC treated with radical intensity‐modulated radiation therapy ± chemotherapy based on the eighth edition TNM. Recursive partitioning analysis (RPA) incorporating pretreatment plasma Epstein–Barr virus (EBV) DNA derived new stage groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived another set of stage groups. Five‐year progression‐free survival (PFS), overall survival (OS) and cancer‐specific survival (CSS) were: Stage I (PFS 100%, OS 90%, CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066 and p = 0.002, respectively). RPA derived four new stages: RPA‐I (T1–T4 N0–N2 & EBV DNA <500 copies per mL; PFS 94%, OS 89%, CSS 96%), RPA‐II (T1–T4 N0–N2 & EBV DNA ≥500 copies per mL; PFS 80%, OS 83%, CSS 89%), RPA‐III (T1–T2 N3; PFS 64%, OS 83%, CSS 83%) and RPA‐IVA (T3–T4 N3; PFS 63%, OS 60% and CSS 68%) (all with p < 0.001). AHR using covariate adjustment also yielded a valid classification (I: T1–T2 N0–N2; II: T3–T4 N0–N2 or T1–T2 N3 and III: T3–T4 N3) (all with p < 0.001). However, RPA stages better predicted survival for PS and CSS after bootstrapping replications. Our RPA‐based stage groups revealed better survival prediction compared to the eighth edition TNM and the AHR stage groups.
A novel SOCS5/miR‐18/miR‐25 axis promotes tumorigenesis in liver cancer
Authors: Sanchez‐Mejias Avencia , Kwon Junsu , Chew Xiao Hong , Siemens Angela , Sohn Hye Seon , Jing Guo , Zhang Bin , Yang Henry , Tay Yvonne
Published: September 2018

The role of miRNAs with tumor suppressive activity in liver cancer has been well studied. However, little is known about potential oncomiRs in HCC. In our study, we conducted a systematic evaluation of candidate oncomiRs and found that upregulation of miR‐18a and miR‐25 in HCC was associated with poor patient survival and promoted proliferation in HCC cell lines. These two miRNAs belong to the polycistronic paralogous miR‐17‐92 and miR‐25‐106b clusters respectively. Although the members of both clusters are often upregulated in HCC, the contribution of individual miRNAs in these clusters to HCC tumorigenesis is not fully understood. We validated SOCS5 as a bona fide target of both miRNAs, and established, for the first time, the tumor suppressive role of SOCS5 in liver cancer. We further investigated the mechanism by which SOCS5 contributes to tumorigenesis, demonstrated that this SOCS5/miR‐18a/miR‐25 axis regulates the tumor suppressor TSC1 and downstream mTOR signaling, and highlighted the potential therapeutic use of miR‐18a and miR‐25 inhibition in restoring SOCS5 levels in HCC.
Zika virus exposure in pregnancy and its association with newborn visual anomalies and hearing loss
Authors: Peloggia Alessandra , Ali Moazzam , Nanda Kavita , Bahamondes Luis
Published: September 2018

Exposure to Zika virus (ZIKV) in pregnancy leads to a spectrum of congenital effects in the newborn. Recent studies have begun to evaluate the impact of ZIKV during pregnancy. Among 39 relevant studies, nine were related specifically to clinical studies of ophthalmologic disorders and one was related to hearing loss impairment; most of these studies were case reports and case series reports. Importantly, congenital toxoplasmosis was ruled out in all studies. The data show that, in addition to microcephaly, ZIKV exposure in pregnancy may result in subtle ocular impairments in the newborn. The most common anomalies are macular pigment mottling and/or chorioretinal atrophy, and optic nerve disorders. Sensorineural hearing loss has also been noted in 5.8% of infants with microcephaly. The effects of ZIKV infection during pregnancy are potentially devastating to the fetus and newborn. Although microcephaly is an important signal, the current information emphasizes the importance of ocular and auditory screenings, otherwise sight and hearing anomalies may be underestimated. Healthcare providers should fully understand the spectrum of anomalies related to ZIKV exposure in pregnancy in order to counsel pregnant women living in high‐risk areas, in addition to those wanting to become pregnant.
Improving the annual yield of a wheat and maize system through irrigation at the maize sowing stage†
Authors: Feng Yupeng , Yang Meng , Shang Mengfei , Jia Hao , Chu Qingquan , Chen Fu
Published: September 2018

To achieve high‐yielding and eco‐friendly crop production, it is crucial to identify the critical water requirement period of crops, especially in annual crop production systems. A 2‐year experiment was established to study the annual yield, total water consumption and water productivity (WP) of a winter wheat (Triticum aestivum L.) and summer maize (Zea mays L.) system in the Huang‐Huai‐Hai Plain.

The results showed that the annual yield of this crop system increased with irrigation frequency and was highest when irrigation was applied three times in the wheat season and once in the maize season (W3M1), though there was no significant difference in annual yield among W2M1, W3M1 and W4M1. And there is no evidence in this paper that irrigation scheduling substantially affects WP. W2M1 had the second highest annual yield (18.7 t ha−1 in 2013–2014 and 19.9 ha−1 in 2014–2015) with a low amount of irrigation compared with W3M1 and W4M1. The highest total water consumption was measured in W3M1 and reached 812 and 873 mm in the first and second years, respectively. Irrigation during the summer maize sowing stage is essential for improving the annual yield and WP. © 2018 John Wiley & Sons, Ltd.
Superparamagnetic graphene quantum dot as a dual‐modality contrast agent for confocal fluorescence microscopy and magnetomotive optical coherence tomography
Authors: Li Wei , Song Wenxing , Chen Biqiong , Matcher Stephen J.
Published: September 2018

A magnetic graphene quantum dot (MGQD) nanoparticle, synthesized by hydrothermally reducing and cutting graphene oxide‐iron oxide sheet, was demonstrated to possess the capabilities of simultaneous confocal fluorescence and magnetomotive optical coherence tomography (MMOCT) imaging. This MGQD shows low toxicity, significant tunable blue fluorescence and superparamagnetism, which can thus be used as a dual‐modality contrast agent for confocal fluorescence microscopy (CFM) and MMOCT. The feasibility of applying MGQD as a tracer of cells is shown by imaging and visualizing MGQD labeled cells using CFM and our in‐house MMOCT. Since MMOCT and CFM can offer anatomical structure and intracellular details, respectively, the MGQD for cell tracking could provide a more comprehensive diagnosis.
Doxorubicin‐loaded poly(ε‐caprolactone)‐Pluronic micelle for targeted therapy of esophageal cancer
Authors: Dai Shujun , Ye Zhimin , Wang Fangzheng , Yan Fengqin , Wang Lei , Fang Jun , Wang Zhun , Fu Zhenfu
Published: September 2018

There is still lack of effective treatment of esophageal cancer, and it is urgently necessary to develop a new programs to treat this disease. More and more evidence suggests that the combination of 2 or more treatment strategies can enhance the antitumor activity in cancer treatment. We have established a new therapeutic strategy that combines doxorubicin‐loaded poly(ε‐caprolactone) (PCL)‐Pluronic micelles and miR‐34a to better combat esophageal cancer. Doxorubicin was loaded into PCL‐Pluronic micelle to achieve better uptake. Confocal microscopy was used to assess in vitro cellular uptake of PCL‐Pluronic micelle. Finally, the in vivo effect of this new combination therapy strategy was also studied. The results showed that PCL‐Plannick micelles significantly enhanced the uptake of doxorubicin in esophageal cancer cells in vitro, thereby improving the accumulation of doxorubicin in the cells. In vitro and in vivo combination of doxorubicin‐loaded PCL‐Pluronic micelles and miR‐34a, achieving a significantly synergistic therapeutic effect over the corresponding single treatment. These results suggested that the combinational therapy based on doxorubicin‐loaded PCL‐Pluronic micelle and miR‐34a may provide a reasonable strategy for improving the outcome of esophageal cancer treatment.
Epigenetic silencing of sonic hedgehog elicits antitumor immune response and suppresses tumor growth by inhibiting the hedgehog signaling pathway in metastatic spine tumors in Sprague‐Dawley rats
Authors: Shi Guang , Zhang Hong , Yu Qiong , Jin Hui , Hu Chun‐Mei , Li Shu‐Chun , Ji You‐Bo
Published: September 2018

Background: Patients with metastatic spine tumors may suffer from pain or neurologic deficit, and the disease may be detected in patients with a known malignancy. Sonic hedgehog (SHH) has received special attention due to its role in cancers. Therefore, this study investigated the effects of epigenetic silencing of SHH on antitumor immune response and tumor growth by regulating the hedgehog (Hh) signaling pathway in metastatic spine tumors.

Methods: Rat models of metastatic spine tumors were successfully established. We first calculated the tumor volume and the inhibition rate of tumor growth to investigate the effect of SHH on tumor growth. Afterwards, immunohistochemistry was used to determine whether proliferation was delayed by SHH depletion, and the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay was conducted to test the changes in the lymphocyte transformation rate in the spleen triggered by SHH silencing. Then, the influence of SHH depletion on immune function was investigated. Later, quantitative reverse transcription polymerase chain reaction and Western blot assay were performed to explore the Hh signaling pathway–related factors. Finally, we added the Hh signaling pathway inhibitor, GDC‐0449, to confirm the role of the pathway in tumor progression.

Results: Initially, we observed that SHH depletion was a negative factor for tumor growth. Afterwards, it was revealed that epigenetic silencing of SHH served as an inhibitor factor for the function of spleen lymphocyte transformation and inflammation while promoting antitumor immune function.

Conclusion: Our preliminary results indicate that epigenetic silencing of SHH elicits an antitumor immune response and suppresses tumor growth by inhibiting the Hh signaling pathway in metastatic spine tumors.
Hairless regulates p53 target genes to exert tumor suppressive functions in glioblastoma
Authors: Brook Lemlem , Palade Patricia , Maatough Anas , Whitfield Graham Kerr , Emeterio Lis San , Hsieh David , Hsieh Jui‐Cheng
Published: September 2018

Glioblastoma (GBM) is the most common malignant brain tumor and is associated with a poor prognosis, with most patients living less than a year after diagnosis. Given that GBM nearly always recurs after conventional treatments, there is an urgent need to identify novel molecular targets. Hairless (HR) is a nuclear factor enriched in the skin and has been previously implicated in hair cycling. HR is also highly expressed in the brain, but its significance is unknown. We found that human hairless gene (HR) expression is significantly decreased in all GBM subtypes compared with normal brain tissue and is predictive of prognosis, which suggests that loss of
HR expression can contribute to GBM pathogenesis. HR was recently discovered to bind to and regulate p53 responsive elements, and thus we hypothesized that HR may have a tumor suppressive function in GBM by modulating p53 target gene expression. We found that HR indeed regulates p53 target genes, including those implicated in cell cycle progression and apoptosis in the GBM‐derived U87 cell line, and restoring
HR expression triggered G2/M arrest and apoptosis. An analysis of sequenced genomes from patients with GBM revealed 10 HR somatic mutations in patients with glioma, two of which are located in the histone demethylase domain of HR. These two mutations, P996S and K1004N, were reconstructed and found to have impaired p53 transactivating properties. Collectively, the results of our study suggest that HR has tumor suppressive functions in GBM, which may be clinically relevant and a potential avenue for therapeutic intervention.
Dihydroartemisinin increases gemcitabine therapeutic efficacy in ovarian cancer by inducing reactive oxygen species
Authors: Yang Shengcai , Zhang Dawei , Shen Na , Wang Guanyi , Tang Zhaohui , Chen Xuesi
Published: September 2018

Ovarian cancer is the major cause of death in women gynecological malignancy and gemcitabine (GEM) is commonly used in related chemotherapy. However, more than 90% GEM is catalyzed into an inactive metabolite 2′‐deoxy‐2′,2′‐difluorouridine by stromal and cellular cytidine deaminase (CDA). Dihydroartemisinin (DHA), which possesses an intramolecular endoperoxide bridge, could be activated by heme or ferrous iron to produce reactive oxygen species (ROS). The excess ROS generation will excite expression of heme oxygenase‐1 and suppress CDA expression. Under low CDA expression, the inactivation of GEM is decreased in turn to exert excellent therapeutic efficiency. Herein, we first studied the ROS generation by DHA in vitro with A2780 cells by means of flow cytometry and confocal laser scanning microscopy. Furthermore, cytotoxicity assay in vitro showed that DHA + GEM had synergistic effect, with molar ratio of DHA and GEM at 10. Eventually, in A2780 ovarian cancer xenograft tumor model, DHA + GEM exhibited significant antitumor efficiency with lower blood toxicity than GEM alone. Noteworthy, the combination treatment group completely eliminated the tumors on day 14.
Sucrose nonfermenting AMPK‐related kinase (SNARK) regulates exercise‐stimulated and ischemia‐stimulated glucose transport in the heart
Authors: Sun Xiang‐Lan , Lessard Sarah J. , An Ding , Koh Ho‐Jin , Esumi Hiroyasu , Hirshman Michael F. , Goodyear Laurie J.
Published: September 2018

The signaling mechanisms mediating myocardial glucose transport are not fully understood. Sucrose nonfermenting AMP‐activated protein kinase (AMPK)‐related kinase (SNARK) is an AMPK‐related protein kinase that is expressed in the heart and has been implicated in contraction‐stimulated glucose transport in mouse skeletal muscle. We first determined if SNARK is phosphorylated on Thr208, a site critical for SNARK activity. Mice were treated with exercise, ischemia, submaximal insulin, or maximal insulin. Treadmill exercise slightly, but significantly increased SNARK Thr208 phosphorylation. Ischemia also increased SNARK Thr208 phosphorylation, but there was no effect of submaximal or maximal insulin. HL1 cardiomyocytes were used to overexpress wild‐type (WT) SNARK and to knockdown endogenous SNARK. Overexpression of WT SNARK had no effect on ischemia‐stimulated glucose transport; however, SNARK knockdown significantly decreased ischemia‐stimulated glucose transport. SNARK overexpression or knockdown did not alter insulin‐stimulated glucose transport or glycogen concentrations. To study SNARK function in vivo, SNARK heterozygous knockout mice (SNARK+/−) and WT littermates performed treadmill exercise. Exercise‐stimulated glucose transport was decreased by ~50% in hearts from SNARK+/− mice. In summary, exercise and ischemia increase SNARK Thr208 phosphorylation in the heart and SNARK regulates exercise‐stimulated and ischemia‐stimulated glucose transport. SNARK is a novel mediator of insulin‐independent glucose transport in the heart.