bluuebunny/crossref_metadata_2025 huggingface dataset:
Churchill,Winston (1874–1965)
Authors: Folly Martin H.
Published: May 2018

Winston Churchill (1874–1965) was a British statesman of the twentieth century. He was prime minister from 1940 to 1945 and from 1951 to 1955. Churchill was a committed defender of the British Empire, and his diplomacy was founded on strong anti‐communism and anti‐Nazism. He opposed the Bolshevik Revolution in Russia and warned against appeasement of Germany in the 1930s. Churchill was also a pragmatic statesman who based his policies on the balance of power. In World War II, he forged close relations with US president Franklin D. Roosevelt, and also found power‐political reasons for a working relationship with Joseph Stalin. After the war, Churchill warned against Soviet expansionism in the “Iron Curtain” speech and advocated the maintenance of an Anglo‐American special relationship. He urged Europe to unite for its own security. As prime minister from 1951 to 1955 his preference for personal diplomacy caused him unsuccessfully to advocate a summit meeting between the leaders of Britain, the United States, and the USSR to ease the tensions of the Cold War.
Crimean War (1853–56)
Authors: Fisher John
Published: May 2018

The Crimean War (1853–56) is often characterized as an avoidable conflict: one which occurred largely due to misunderstandings between the Great Powers and between those powers and the Ottoman Empire. Its much debated origins lay in the mutual suspicions held by statesmen particularly concerning the future of the weakening Ottoman Empire. It was fought principally for strategic security but economic and religious interests were also factors, as was prestige. Russia's defeat, and the Treaty of Paris which ended the war, did not lead to an enduring peace in the Near East.
H
ussein,
K
ing (1935–99)
Authors: Ashton Nigel
Published: May 2018

King Hussein (1935–99) was a central figure in the diplomacy of the Arab–Israeli conflict between his accession to the throne of Jordan in 1953 and his death in 1999. In addition to his role in the public diplomacy of the conflict, he also maintained a covert dialogue with Israeli leaders beginning in 1963 and continuing until the early 1990s. In October 1994 he signed a peace treaty with Israel alongside Israeli prime minister Yitzhak Rabin. He also maintained a close alliance with the United States, although relations were strained by his stance over the Camp David accords in 1978 and his response to the Iraqi invasion of Kuwait in 1990. Shortly before his death he changed the line of succession in favor of his son, Abdullah, the current king of Jordan.
James (Jaime)IIofAragon (1267–1327)
Authors: Péquignot Stéphane
Published: May 2018

James (Jaime) II was king of Aragon, count of Barcelona and king of Valencia between 1291 and 1327. Marked by important conflicts, his reign was also characterized by exceptional activity in terms of diplomacy. This took three main directions: the papacy and Italy; the neighboring kingdoms of France and Castile; and the Muslim powers in the Mediterranean. James's diplomacy was based on the keeping of important records, information gathering, and expert support. It was this combination which allowed him to prepare successfully the conquest of Sardinia. James II leaves us with a paradoxical image: a king of peace and a master of double game.
John ofGaunt (1340–99)
Authors: Huffman Joseph P.
Published: May 2018

Remembered more for his diplomacy than for his military campaigns during the era of the Hundred Years' War, John of Gaunt (1340–99) served as a mediator in several international contexts. He not only sought to bridge the divide at home between the Lords Appellant and his troubled nephew, King Richard II, but as Duke of Lancaster John also pursued his own independent diplomatic ventures with the royal courts of France, Portugal, and Castile. Though unsuccessful at saving his nephew's kingship, he otherwise made significant contributions towards peace between England and France, the healing of the Great Schism of the Latin church, and a hoped‐for European‐wide crusade against the Turks, while also securing for his own family a dynastic marriage with the kingdom of Castile through the Treaty of Bayonne (1388). An astute negotiator, he deserves a better reputation than that often cited in the biased opinion of Philippe de Mézières.
Monteiro,Armindo (1896–1955)
Authors: Stone Glyn
Published: May 2018

Armindo Monteiro (1896–1955) served respectively as Portugal's minister of colonies, foreign minister, and ambassador at London. It was as foreign minister that he came to prominence as an international figure. At the beginning of the Spanish Civil War he oversaw Portugal's adhesion to the Spanish Non‐Intervention Agreement and membership of the Spanish Non‐Intervention Committee. As ambassador he represented Portuguese interests on that committee. Though suspicious as to the degree of Britain's commitment to the defense of the Portuguese Empire under the Anglo‐Portuguese Alliance, he was a committed Anglophile. He encouraged Britain's greater involvement in Portuguese affairs in the later 1930s and the early years of the Second World War and supported her efforts to counter German and Italian influence within Portugal. He worked assiduously to repair the damage done to Anglo‐Portuguese relations during the Timor Crisis of 1941–42 and played an important part in the last months of his tenure as ambassador to bring the Atlantic Bases deal of August 1943 to a successful conclusion.
NapoleonI(1769–1821)
Authors: Heinzen Jasper
Published: May 2018

Napoleon I (1769–1821) was a French general and emperor who conquered much of continental Europe at the start of the nineteenth century. He initiated many lasting reforms in civil administration but also pursued war for the aggrandizement of his own power and glory. The Napoleonic Wars (1803–15) are named after him.
Oldenbarnevelt,Johanvan(1547–1619)
Authors: Onnekink David
Published: May 2018

Johan van Oldenbarnevelt (1547–1619) was a statesman who became one of the central figures in the creation of the Dutch Republic and the revolt against Spain (1568–1648). He was instrumental in the conclusion of the first international treaties negotiated by the Dutch Republic and in the forging of the new state's political institutions. He became locked in conflict with the Dutch Stadholder over the direction of foreign policy during the Twelve Years' Truce (1609–21) and was executed for high treason in 1619.
Richelieu,Cardinal (1585–1642)
Authors: Osborne Toby
Published: May 2018

Cardinal Richelieu (1585–1642) was the dominant French minister from 1624 until 1642, controlling French foreign policies. His principal aim was to defend French interests as he defined them, against the perceived ambitions of the Habsburgs. This entailed addressing domestic challenges and engaging in a series of surrogate wars in northern Europe, north Italy, and the Holy Roman Empire, before the outbreak of formal war with Spain in 1635. While Richelieu has often been seen as an amoral, even Machiavellian, political figure, he was on the contrary guided by a sense of moral duty to France as a leading power in a Europe underpinned by peace and stability.
Sadat,Anwar (1918–81)
Authors: Lefebvre Jeffrey A.
Published: May 2018

During his eleven years (1970–81) as president of Egypt, Anwar Sadat (1918–81) dramatically altered Egyptian foreign (and domestic) policy. Sadat believed the path to regaining control of the Sinai Peninsula, occupied by Israel since the June 1967 war, ran through Washington. Only the Americans could pressure the Israelis to return the Sinai Peninsula. Coupled with his distrust of the Soviet Union, in the aftermath of the October 1973 Arab–Israeli War, Sadat realigned Egypt with the United States. Sadat also broke ranks with the Arab League, concerned that maintaining a non‐compromising united front position vis‐à‐vis Israel would prevent him from pursuing an Egypt‐first unilateral peace process with Israel. Sadat's diplomacy ultimately led to the signing of a peace treaty with Israel in March 1979. For this Sadat paid with his life. He was assassinated during a military parade in October 1981 by members of the Gama'a Islamiyya (Islamic Group).
Saladin (1138–93)
Authors: Huffman Joseph P.
Published: May 2018

Saladin (Ṣalāḥ ad‐Dīn Yūsuf ibn Ayyūb) used diplomacy to achieve what risky open battle might not. He not only fought Western crusaders but also both Fatimid and Zengid factions in his effort to reunite Egypt and Syria with the Abassid caliphate. Masterful in using an anti‐crusader jihad as a unifying force for all Muslim factions, he nonetheless leveraged a temporizing truce with Richard I of England (Treaty of Ramla) to end the Third Crusade. Such diplomacy brought harsh criticism from Muslim detractors but ultimately assured Muslim hegemony in Palestine. Saladin's diplomatic behavior led Dante to place Saladin in limbo as a “virtuous pagan,” from which Sir Walter Scott fashioned a romanticized modern mythology of Saladin as the atypical moral Muslim to criticize the crusading movement. Its grip on Western historiography and popular memory has only since the 1980s been supplanted by a more balanced understanding of Saladin and his use of diplomacy.
William ofOrange (1650–1702)
Authors: Onnekink David
Published: May 2018

William of Orange (1650–1702) was Stadholder in the Dutch Republic (1672–1702) and king of England, Scotland, and Ireland (1689–1702). He emerged in 1672 as the leader of the Dutch Republic after the Anglo‐French assault and became the spearhead of an international coalition against France during the 1680s. In the process of containing France a balance of power, in effect, emerged in Europe. William was one of the first to make extensive use of propaganda in diplomatic campaigns in order to swing public opinion in his favor.
Y
amagata
A
ritomo (1838–1922)
Authors: Boyd James
Published: May 2018

Although not a diplomat, Yamagata Aritomo (1838–1922) was an extremely important figure in early modern Japan both in terms of his career as a solider and then as a politician. In his first career he oversaw the creation of the modern Japanese army and then in the second, as a politician held a number of important cabinet posts and served as prime minister on two occasions.
Messana Crisis of 264bce
Authors: Hoyos Dexter
Published: May 2018

In summer 264bcethe Mamertines of Messana, Sicily, sought help from both Carthage and Rome against attack by Syracuse. Each responded, the Carthaginians at once deterring the Syracusans from a direct attack on Messana, and the Romans then sending an army. Carthage opposed Rome's involvement, allying instead with Syracuse to renew the attack on Messana. Both rejected overtures by the consul Appius Claudius for a peaceful settlement. When Appius crossed to Sicily, he repelled each besieging force in turn before moving south against Syracuse. What Rome seems to have originally envisaged as a war with that city‐state had by then become a war with Carthage as well: the First Punic War.
Peter thePatrician (c. 500–c. 565)
Authors: Lee A. D.
Published: May 2018

Peter the Patrician (c. 500–c. 565) served under the sixth‐century Roman emperor Justinian as an envoy to the Goths and Persians and as “Master of the Offices” – a senior post whose duties included oversight of important aspects of imperial diplomacy. He wrote accounts of aspects of his diplomatic activities, excerpts from which have survived to provide important insights into the conduct of diplomacy in this period.
FrancisI(1494–1547)
Authors: Shaw Christine
Published: May 2018

The conflict of King Francis I of France (1494–1547) with the Emperor Charles V on several fronts was the focus of his diplomacy, as he tried to stir up trouble for the emperor and build up alliances against him. Most controversially, he allied with German Protestant princes and with the Ottoman sultan Suleiman in his attempts to undermine Charles.
Is bad intent negligible? Linking victim justice sensitivity, hostile attribution bias, and aggression
Authors: Bondü Rebecca
Published: May 2018

The hostile attribution bias (HAB) is a well‐established risk factor for aggression. It is considered part of the suspicious mindset that may cause highly victim‐justice sensitive individuals to behave uncooperatively. Thus, links of victim justice sensitivity (JS) with negative behavior, such as aggression, may be better explained by HAB. The present study tested this hypothesis inN = 279 German adolescents who rated their JS, HAB, and physical, relational, verbal, reactive, and proactive aggression. Victim JS predicted physical, relational, verbal, reactive, and proactive aggression when HAB was controlled. HAB only predicted physical and proactive aggression. There were no moderator effects. Injustice seems an important reason for aggression irrespective of whether or not it is intentionally caused, particularly among those high in victim JS. Thus, victim JS should be considered as a potential important risk factor for aggression and receive more attention by research on aggression and preventive efforts.
Geophagic earths consumed by women in western Kenya contain dangerous levels of lead, arsenic, and iron
Authors: Miller Joshua D. , Collins Shalean M. , Omotayo Moshood , Martin Stephanie L. , Dickin Katherine L. , Young Sera L.
Published: May 2018

Objectives

Geophagy is commonly reported by pregnant women and children, yet its causes and consequences remain poorly understood. Therefore, we sought to determine if geophagy could contribute micronutrients and/or be a source of heavy metal exposure by examining the elemental composition of earths consumed in Kakamega, Kenya.

Methods

Ten samples of earths commonly consumed during pregnancy were collected by study enumerators and analyzed using inductively coupled plasma‐atomic emission spectroscopy. Samples were either collected at markets or from walls of participants' homes, based on where participants reported most commonly sourcing their consumed earths.

Results

Based on estimated intakes (40 g/day), all samples had lead levels that exceeded the provisional maximum tolerable daily intake, and one sample exceeded the threshold for arsenic. Further, estimated intakes of iron for all samples were at least 8.9 times higher than the established threshold. Elemental concentrations were also compared by the site of sample collection (market vs. household wall); market samples had significantly higher iron concentrations and lower calcium concentrations than wall samples.

Conclusions

Geophagic earths in Kakamega may be harmful because of dangerously high levels of lead, arsenic, and iron. The prevalence of geophagy among vulnerable populations underscores the importance of understanding its causes and consequences for accurate public health messaging.
Surviving in the urban–rural interface: Feeding and ranging behavior of brown howlers (Alouatta guariba clamitans) in an urban fragment in southern Brazil
Authors: Corrêa Fabiana M. , Chaves Óscar M. , Printes Rodrigo C. , Romanowski Helena P.
Published: May 2018

Wild primates that live in urban areas face extreme threats that are less frequent in nonurban fragments, such as the presence of dangerous matrix elements (e.g., roads, power lines, buildings, and a high density of domestic dogs near food patches), that could influence their movements, feeding behavior, and survival. However, the scarcity of studies addressing this issue hinders our understanding of the behavioral adjustments that favor the survival of primates in urban areas. For 12 months, we studied a six‐individual group of brown howlers (Alouatta guariba clamitans) in an urban fragment to determine (i) their diet richness and its relationships with food availability, (ii) their daily path length (DPL) and the matrix elements used during movement, and (iii) the main ecological drivers of the DPL. Sampling effort totaled 72 days, 787 hr, and 3,224 instantaneous scans. We found that the diet of brown howlers contained 35 plant species (including seven cultivated crops) belonging to 33 genera and 21 families. The consumption of fruits and young leaves was directly related to their temporal availability. The average DPL (446 m) was smaller than that reported for groups of howlers inhabiting large nonurban fragments. To move between food patches, animals used three main matrix elements: trees, power lines, and roofs. The number of plant species used during the day was the main driver of DPL. Our findings highlighted that the generalist‐opportunistic diet of brown howlers and their ability to move across the anthropogenic matrix using artificial elements such as power lines, roofs, and wildlife crossings represent a remarkable part of their behavioral repertory in Lami. However, there are potential costs associated with these strategies, namely, electrocution and predation by domestic dogs. Thus, it is urgent to further investigate how these behaviors could affect the long‐term survival of these animals.
A Minimal Functional Complex of Cytochrome P450 and FBD of Cytochrome P450 Reductase in Nanodiscs
Authors: Prade Elke , Mahajan Mukesh , Im Sang‐Choul , Zhang Meng , Gentry Katherine A. , Anantharamaiah G. M. , Waskell Lucy , Ramamoorthy Ayyalusamy
Published: May 2018

Structural interactions that enable electron transfer to cytochrome‐P450 (CYP450) from its redox partner CYP450‐reductase (CPR) are a vital prerequisite for its catalytic mechanism. The first structural model for the membrane‐bound functional complex to reveal interactions between the full‐length CYP450 and a minimal domain of CPR is now reported. The results suggest that anchorage of the proteins in a lipid bilayer is a minimal requirement for CYP450 catalytic function. Akin to cytochrome‐b5 (cyt‐b5), Arg 125 on the C‐helix of CYP450s is found to be important for effective electron transfer, thus supporting the competitive behavior of redox partners for CYP450s. A general approach is presented to study protein–protein interactions combining the use of nanodiscs with NMR spectroscopy and SAXS. Linking structural details to the mechanism will help unravel the xenobiotic metabolism of diverse microsomal CYP450s in their native environment and facilitate the design of new drug entities.
Übergangsmetallkatalysierte Carboxylierungen mit Kohlendioxid
Authors: Tortajada Andreu , Juliá‐Hernández Francisco , Börjesson Marino , Moragas Toni , Martin Ruben
Published: May 2018

In den letzten Jahren hat das Interesse an katalytischen Reaktionen zum Einbau von CO2 als allgegenwärtigem und preisgünstigem C1‐Rohstoff in organischen Stoffen aufs Neue zugenommen. Obgleich C‐C‐Kupplungen durch katalytische CO2‐Fixierung für lange Zeit eher begrenzt waren, zeigt die nähere Betrachtung der neueren Literatur, dass katalytische Carboxylierungen in eine Epoche exponentiellen Wachstums eingetreten sind. Es ist das Entstehen einer umfassenden Disziplin abzusehen, die eine Optimierung der Synthese von Carbonsäuren erlaubt, welche äußerst wichtige Zwischenprodukte in industriellen Prozessen darstellen. Die neuen Strategien sind generell breit anwendbar und leicht durchzuführen, jedoch bestehen nach wie vor erhebliche Herausforderungen. Aus diesem Grund werden die metallkatalysierten Carboxylierungen hier auf konzeptionelle und übersichtliche Weise abgehandelt, um ihre grundlegenden Prinzipien aufzuzeigen.
Boronic Acids as Bioorthogonal Probes for Site‐Selective Labeling of Proteins
Authors: Akgun Burcin , Hall Dennis G.
Published: May 2018

Over the past two decades, bioorthogonal chemistry has become a preferred tool to achieve site‐selective modifications of proteins. However, there are only a handful of commonly applied bioorthogonal reactions and they display some limitations, such as slow rates, use of unstable or cytotoxic reagents, and side reactions. Hence, there is significant interest in expanding the bioorthogonal chemistry toolbox. In this regard, boronic acids have recently been introduced in bioorthogonal chemistry and are exploited in three different strategies: 1) boronic ester formation between a boronic acid and a 1,2‐cis diol; 2) iminoboronate formation between 2‐acetyl/formyl‐arylboronic acids and hydrazine/hydroxylamine/semicarbazide derivatives; 3) use of boronic acids as transient groups in a Suzuki–Miyaura cross‐coupling or other reactions that leave the boronyl group off the conjugation product. In this Review, we summarize progress made in the use of boronic acids in bioorthogonal chemistry to enable site‐selective labeling of proteins and compare these methods with the most commonly utilized bioorthogonal reactions.
Renewable Polyethers via GaBr3‐Catalyzed Reduction of Polyesters
Authors: Dannecker Patrick‐Kurt , Biermann Ursula , von Czapiewski Marc , Metzger Jürgen O. , Meier Michael A. R.
Published: May 2018

Herein, a novel approach is reported for the synthesis of medium‐ and long‐chain aliphatic polyethers 2 based on the GaBr3‐catalysed reduction of polyesters 1 with TMDS as the reducing agent. Thus, various linear and branched aliphatic polyesters 1 were prepared and systematically investigated for this reduction strategy, demonstrating the applicability and versatility of this new polyether synthesis protocol. Medium‐ and long‐chain chain polyethers were obtained from the respective polyesters without or with minor chain degradation, whereas short‐chain polyesters, such as poly‐l‐lactide 1 i and poly[(R)‐3‐hydroxybutanoate] 1 j, showed major chain degradation. In this way, previously unavailable and uncommon polyethers were obtained and studied.
An experimental investigation on pressure response and phase transition of supercritical carbon dioxide releases from a small‐scale pipeline
Authors: Yan Xingqing , Zhu Hailong , Yu Jianliang , Chen Shaoyun , Mahgerefteh Haroun
Published: May 2018

The prediction of the pressure response and phase transition in the event of an accidental carbon dioxide (CO2) release from a ruptured pipeline is of significant importance for understanding the depressurization behaviour and hence the fracture behaviour. This article presented a small‐scale experimental investigation on the pressure response and phase transition of supercritical CO2 release from a pressurized pipeline with a relief orifice. High‐frequency transducers and thermocouples were used to measure the evolution of CO2 pressures and temperatures at different locations after release. The results indicated that pressures at different locations decreased nearly synchronously after release. No vapour bubble and pressure rebound generated in larger scale release experiments were found in our small‐scale release experiments. The depressurization rate was greatly affected by the phase transition. During the release process, the supercritical CO2 firstly turned into an unstable gas with a very great depressurization rate, then changed into the gas–liquid phase with a lower depressurization rate, and finally changed into gaseous CO2. The larger the relief diameter was, the longer the gas–liquid phase state lasted.
Cellular energy metabolism maintains young status in old queen honey bees (Apis mellifera)
Authors: Lu Cheng‐Yen , Qiu Jiantai Timothy , Hsu Chin‐Yuan
Published: May 2018

Trophocytes and oenocytes of queen honey bees are used in studies of cellular longevity, but their cellular energy metabolism with age is poorly understood. In this study, the molecules involved in cellular energy metabolism were evaluated in the trophocytes and oenocytes of young and old queen bees. The findings indicated that there were no significant differences between young and old queen bees in β‐oxidation, glycolysis, and protein synthesis. These results indicate that the cellular energy metabolism of trophocytes and oenocytes in old queen bees is similar to young queen bees and suggests that maintaining cellular energy metabolism in a young status may be associated with the longevity of queen bees. Fat and glycogen accumulation increased with age indicating that old queen bees are older than young queen bees.
Nickel‐Catalyzed Regioselective C(2)−H Difluoroalkylation of Indoles with Difluoroalkyl Bromides
Authors: Soni Vineeta , Sharma Dipesh M. , Punji Benudhar
Published: May 2018

Regioselective C(2)−H difluoroalkylation of C‐3 unsubstituted indoles with commonly available fluoroalkyl bromides is successfully achieved employing a simple nickel catalyst system, (DME)NiCl2/Xantphos. This methodology shows excellent regioselectivity and exhibits a broad substrate scope. Various functional groups, such as ‐OMe, ‐F, and ‐Br, are tolerated on the indole backbone to give the difluoroalkylated products in moderate to good yields. Preliminary mechanistic findings demonstrate that the reaction is homogeneous in nature and involves a radical manifold. Synthetic utility of this nickel‐catalyzed method is demonstrated by synthesizing melatonin receptor antagonist Luzindole derivative.
Stakeholder pressures and corporate climate change mitigation strategies
Authors: Cadez Simon , Czerny Albert , Letmathe Peter
Published: May 2018

Climate change mitigation and its related reduction of greenhouse gas (GHG) emissions is one of the most important challenges facing society. The major cause of the problem and the key to its solution are GHG‐intensive firms that emit vast amounts of anthropogenic GHG emissions. The study reported herein aims to increase our understanding of the climate change mitigation strategies of these firms, in particular their antecedents and effects. A comprehensive conceptual model is proposed and tested empirically based on a survey of 247 firms that participated in the European Union's Emissions Trading Scheme in the first two trading periods. We find that market pressures for reducing GHG emissions, perceived GHG‐related regulatory uncertainty and environmental strategy focus are important determinants of corporate GHG reduction strategies which, in turn, enhance GHG‐related performance. We also show that the results vary depending on the type of emissions.
New Flavonoid Glucuronate Esters with Anti‐inflammatory Activities from Scutellaria regeliana
Authors: Han Qing‐Tong , Xiao Kai , Xiang Kang‐Lin , Li Gui‐Sheng , Dai Sheng‐Jun
Published: May 2018

Two new flavonoid glucuronate esters, named scuregeliosides A and B (1 and 2), as well as three known ones, chrysin‐7‐O‐β‐d‐glucuronic acid methyl ester (3), 5,7,4′‐trihydroxyflavone‐8‐O‐β‐d‐glucuronic acid methyl ester (4) and apigenin‐7‐O‐β‐d‐glucuronic acid ethyl ester (5), were isolated from the ethanolic extract of the whole plant of Scutellaria regeliana. Their chemical structures were elucidated on the basis of comprehensive spectroscopic analyses. Five compounds were screened for anti‐inflammatory activity in vitro. As the results, the inhibition rates of release of β‐glucuronidase from rat polymorphonuclear leukocytes were in the range of 42.2 – 47.1% at a concentration of 10 μm.
Structural Insight into the Allosteric Coupling of Cu1 Site and Trinuclear Cu Cluster in CotA Laccase
Authors: Xie Tian , Liu Zhongchuan , Wang Ganggang
Published: May 2018

In laccase, type 1 copper (Cu1) was connected to the trinuclear copper center (TNC) by the conserved Cys–His bridge. An allosteric coupling between the two redox sites has been reported; however, the molecular mechanism underlining the allosteric coupling is unknown. In this study, ligands of the two type 3 copper sites, including His491 and His493, in CotA were mutated to Cys or Ala. The crystal structures revealed that mutations at His491 and His493 caused rearrangement of the hydrogen‐bond network and geometric distortion of the TNC, which severely impaired the activities of mutants H493A, H493C, and H491C. In addition, the change in TNC affected hydrogen bonds around Cys492 in the mutants and led to Cu1 being partially reduced. These results not only decipher the mechanism of allosteric coupling between Cu1 and TNC in laccase, but also pave the way for laccase protein engineering.
Selenium‐Based Nanozyme as Biomimetic Antioxidant Machinery
Authors: Huang Yanyan , Liu Zhen , Liu Chaoqun , Zhang Yan , Ren Jinsong , Qu Xiaogang
Published: May 2018

A self‐assembly nanocomposite was designed to mimic intracellular enzymatic and non‐enzymatic antioxidants‐constituted antioxidant defense machinery. In this work, selenium nanocomponent served as one model to mimic antioxidant enzyme, whereas polydopamine was able to mimic non‐enzymatic antioxidant biomolecule in living systems. With the excellent glutathione peroxidase‐mimic capacity of selenium and the reducibility of polydopamine, this Se@pDA nanozyme could achieve synergetic antioxidative efficiency to protect cellular components against oxidative damage. The pneumonia model of mice further proved the potential of our nanocomposites for anti‐inflammation therapy.
Metal‐Free Acetylene Coupling by the (C6F5)2B−X 1,2‐Halogenoboration Reaction
Authors: Ueno Atsushi , Li Jun , Daniliuc Constantin G. , Kehr Gerald , Erker Gerhard
Published: May 2018

(C6F5)2B‐halides were conveniently prepared by treatment of (C6F5)2BH with tritylchloride or ‐bromide, respectively. With cyclopropylacetylene, (C6F5)2BBr underwent sequential cis‐1,2‐halogenoboration followed by 1,2‐carboboration to give the 4‐bromo‐2,4‐dicyclopropylbutadienyl‐B(C6F5)2 product. It reacted further with additional cyclopropylacetylene to give the linear triene and tetraene products in a metal‐free alkyne oligomerization reaction. The pyridine adduct of the initial diene product was characterized by X‐ray diffraction. (C6F5)2BCl reacted analogously. Similar (C6F5)2BX induced oligomerization reactions were carried out with two conjugated enynes.
Enantiomeric composition of nicotine in tobacco leaf, cigarette, smokeless tobacco, and e‐liquid by normal phase high‐performance liquid chromatography
Authors: Zhang Hongfei , Pang Yongqiang , Luo Yanbo , Li Xiangyu , Chen Huan , Han Shulei , Jiang Xingyi , Zhu Fengpeng , Hou Hongwei , Hu Qingyuan
Published: May 2018

Evaluating the source of nicotine in e‐liquid is a problem. Tobacco‐derived nicotine contains predominantly (S)‐(−)‐nicotine, whereas tobacco‐free nicotine products may not. Thus, we developed a new normal phase high‐performance liquid chromatography method to determinate the enantiomeric composition of nicotine in 10 kinds of flue‐cured tobacco, 3 kinds of burley, 1 kind of cigar tobacco, 2 kinds of oriental tobacco, 5 kinds of Virginia cigarette, 5 kinds of blend cigarette, 10 kinds of e‐liquid, and 4 kinds of smokeless tobacco. The amount of (R)‐(+)‐nicotine ranged from ~0.02% to ~0.76% of total nicotine. An e‐liquid sample had the highest level of (R)‐(+)‐nicotine. The extraction and purification processes used to obtain commercial (S)‐(−)‐nicotine from the tobacco do not decrease the amount of (R)‐(+)‐nicotine in tobacco. So the amount of (R)‐(+)‐nicotine in samples in our work were the same as tobacco samples.
Fragment‐Based Phenotypic Lead Discovery: Cell‐Based Assay to Target Leishmaniasis
Authors: Ayotte Yann , Bilodeau François , Descoteaux Albert , LaPlante Steven R.
Published: May 2018

A rapid and practical approach for the discovery of new chemical matter for targeting pathogens and diseases is described. Fragment‐based phenotypic lead discovery (FPLD) combines aspects of traditional fragment‐based lead discovery (FBLD), which involves the screening of small‐molecule fragment libraries to target specific proteins, with phenotypic lead discovery (PLD), which typically involves the screening of drug‐like compounds in cell‐based assays. To enable FPLD, a diverse library of fragments was first designed, assembled, and curated. This library of soluble, low‐molecular‐weight compounds was then pooled to expedite screening. Axenic cultures of Leishmania promastigotes were screened, and single hits were then tested for leishmanicidal activity against intracellular amastigote forms in infected murine bone‐marrow‐derived macrophages without evidence of toxicity toward mammalian cells. These studies demonstrate that FPLD can be a rapid and effective means to discover hits that can serve as leads for further medicinal chemistry purposes or as tool compounds for identifying known or novel targets.
Trends in incidence and 5‐year mortality in men with newly diagnosed, metastatic prostate cancer—A population‐based analysis of 2 national cohorts
Authors: Helgstrand John T. , Røder Martin A. , Klemann Nina , Toft Birgitte G. , Lichtensztajn Daphne Y. , Brooks James D. , Brasso Klaus , Vainer Ben , Iversen Peter
Published: May 2018

BACKGROUND

Early detection has increased prostate cancer (PCa) incidence. Randomized trials have demonstrated that early detection reduces the incidence of de novo metastatic PCa. Concurrently, life‐prolonging treatments have been introduced for patients with advanced PCa. On a populations‐based level, the authors analyzed whether early detection and improved treatments changed the incidence and 5‐year mortality of men with de novo metastatic PCa.

METHODS

Men diagnosed with PCa during the periods 1980 to 2011 and 1995 to 2011 were identified in the US Surveillance, Epidemiology, and End Results (SEER) program and the Danish Prostate Cancer Registry (DaPCaR), respectively, and stratified according to period of diagnosis. Age‐standardized incidence rates were calculated. Five‐year mortality rates for de novo metastatic PCa were analyzed using competing risk analysis.

RESULTS

Totals of 426,266 and 47,024 men were identified in SEER and DaPCaR, respectively. Of these, 29,555 and 6874 had de novo metastatic PCa. The incidence of de novo metastatic PCa decreased (from 12.0 to 4.4 per 100,000 men) in the SEER cohort (1980‐2011), whereas it increased (from 6.7 to 9.9 per 100,000 men) in the DaPCaR cohort (1995‐2011). Five‐year PCa mortality in the SEER cohort was stable for men diagnosed with de novo metastatic PCa from 1980 to 1994 and increased slightly in the latest periods studied (P < .0001), whereas it decreased by 16.6% (P < .0001) in the DaPCaR cohort.

CONCLUSIONS

Despite earlier detection, de novo metastatic PCa remains associated with a high risk of 5‐year disease‐specific mortality. The reduced 5‐year PCa mortality in the Danish cohort is largely explained by lead‐time. Early detection strategies do indeed decrease the incidence of de novo metastatic PCa, as observed in the SEER cohort. This achievement, however, must be weighed against the unsolved issue of overdetection and overtreatment of indolent PCa. Cancer 2018;124:2931‐8. © 2018 American Cancer Society.
Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: Recommendations for clinical practice from the French Chronic Myeloid Leukemia Study Group
Authors: Rea Delphine , Ame Shanti , Berger Marc , Cayuela Jean‐Michel , Charbonnier Aude , Coiteux Valérie , Cony‐Makhoul Pascale , Dubruille Viviane , Dulucq Stéphanie , Etienne Gabriel , Legros Laurence , Nicolini Franck , Roche‐Lestienne Catherine , Escoffre‐Barbe Martine , Gardembas Martine , Guerci‐Bresler Agnès , Johnson‐Ansah Hyacinthe , Rigal‐Huguet Françoise , Rousselot Philippe , Mahon François‐Xavier ,   for the French Chronic Myeloid Leukemia Study Group
Published: May 2018

BACKGROUND

The ultimate goal of chronic myeloid leukemia management in the tyrosine kinase inhibitor (TKI) era for patients who obtain deep molecular responses is maintaining a durable off‐treatment response after treatment discontinuation; this situation is called treatment‐free remission (TFR). Knowledge accumulated during the last 10 years justifies moving TFR strategies from research to clinical practice.

METHODS

Twenty experts from the French Chronic Myeloid Leukemia Study Group (France Intergroupe des Leucémies Myéloïdes Chroniques), including 17 hematologists, 2 molecular biologists, and 1 cytogeneticist, critically reviewed published data with the goal of developing evidence‐based recommendations for TKI discontinuation in clinical practice.

RESULTS

Clinically relevant questions were addressed, including the selection of candidate patients (with known prognostic factors for outcomes taken into account), detailed monitoring procedures during the treatment‐free phase, a definition of relapse requiring therapy resumption, and monitoring after treatment reintroduction.

CONCLUSIONS

This work presents consensus statements with the aim of guiding physicians and biologists by means of pragmatic recommendations for safe TKI discontinuation in daily practice. Cancer 2018;124:2956‐63. © 2018 American Cancer Society.
Rationale and emerging strategies for immune checkpoint blockade in soft tissue sarcoma
Authors: Wisdom Amy J. , Mowery Yvonne M. , Riedel Richard F. , Kirsch David G.
Published: May 2018

Soft tissue sarcomas (STS) are heterogeneous, mesenchymal malignancies with variable biologic behavior. The primary management for localized STS is surgical resection, which may be combined with neoadjuvant or adjuvant radiation therapy to increase the probability of achieving local control. Many patients with large, high‐grade STS develop metastatic disease. Several clinical trials of immune checkpoint blockade for STS have produced promising responses in patients with metastatic disease. In this review, recent and ongoing clinical trials of immune checkpoint inhibition for STS are discussed. The authors explain the rationale for immune checkpoint inhibition and radiation therapy and highlight new studies testing this combination in the neoadjuvant setting for patients with high‐risk STS. In addition, they describe novel combinations of immunotherapy with targeted therapies and chemotherapies being tested in the metastatic setting and discuss how these combinations have the potential to be integrated into adjuvant therapy in the future.
Does Dapagliflozin Affect Energy Intake and Appetite? A Randomized, Controlled Exploratory Study in Healthy Subjects
Authors: Bertran Elizabeth , Berlie Helen D. , Nixon Aaron , Jaber Linda
Published: May 2018

The primary aims of this study were to assess the effects of dapagliflozin versus placebo on energy intake and appetite ratings in healthy individuals. This was a randomized, single‐blind, placebo‐controlled, 2‐period crossover study. In each period, healthy individuals received either dapagliflozin or placebo for 2 weeks. On assessment days, participants were asked to consume a standard preload breakfast. Appetite ratings were measured with 100‐mm visual analog scales immediately before and during the 4.25‐hour period after breakfast. Energy intake was measured at an ad libitum lunch. Energy intake and appetite responses were assessed at the end of each 2‐week treatment period by mixed‐design analysis of variance. Eighteen individuals completed all assessments (44% female; mean age, 22.8 years; 44% Caucasian; mean BMI, 25.2 kg/m2). There was no difference in energy intake on dapagliflozin compared to placebo (mean difference, −19.8 kcal; P = .516). Mean differences in prebreakfast desire for salty foods (11.3 mm, P = .094) and postbreakfast desire for sweet foods (8.1 mm, P = .054) trended higher with dapagliflozin relative to placebo. Our data do not support an effect of dapagliflozin on energy intake or appetite measures in young, healthy subjects. Although not statistically significant, the size of the mean differences in prebreakfast desire for salty foods and postbreakfast desire for sweet foods on dapagliflozin were larger than placebo and reflect the drug's natriuretic and glucuretic effects. These findings should be further evaluated in patients with type 2 diabetes.
Pharmacokinetic and Pharmacodynamic Correlations From 2 Studies Evaluating Abuse Potential of Hydrocodone Extended‐Release Tablets
Authors: Schoedel Kerri A. , Gillespie Michael , Levy‐Cooperman Naama , Shram Megan J. , Rabinovich‐Guilatt Laura
Published: May 2018

Pharmacokinetic (PK)/pharmacodynamic (PD) correlations were explored in 2 human abuse potential studies of orally and intranasally administered hydrocodone extended‐release (ER) 45 mg in healthy, nondependent opioid users. In a crossover study design, subjects received intact hydrocodone ER, finely milled hydrocodone ER, and hydrocodone powder in solution in the oral study and finely milled hydrocodone ER, hydrocodone powder, and finely milled Zohydro® ER in the intranasal study. Spearman ρ2 and Pearson r2 values were calculated for PD (maximum effect [Emax] for “at the moment” Drug Liking, Overall Drug Liking, and Take Drug Again visual analog scales [VAS]) vs PK (partial area under the concentration‐time curve [AUC], maximum drug concentration [Cmax], time to Cmax [Tmax], and abuse quotient [PK AQ; Cmax/Tmax]) for all treatments. In the oral study, correlations were strongest between Emax of “at the moment” Drug Liking and PK parameters (Cmax [ρ2 = 0.4446], PK AQ [ρ2 = 0.5179], Tmax [ρ2 = 0.5093], and early systemic exposure [ρ2 = 0.4782]). For Overall Drug Liking and Take Drug Again VAS, ρ2 values for correlations with PK parameters ranged from 0.2620 to 0.3637. In the intranasal study, no clear correlations between PK and PD parameters were apparent.
Independent directors' background and CSR disclosure
Authors: Fernández‐Gago Roberto , Cabeza‐García Laura , Nieto Mariano
Published: May 2018

This paper extends research on how the background of independent directors may affect the way in which their companies disclose information about corporate social responsibility (CSR). Using a sample of 83 Spanish‐listed firms over the period 2009–2014, the findings of a random effects probit model suggest that, in addition to board independence, having independent directors with political backgrounds and diverse education has a positive impact on their firm's probability of issuing a CSR report following the standards of the Global Reporting Initiative.
Molecular Simulation Results on Charged Carbon Nanotube Forest‐Based Supercapacitors
Authors: Muralidharan Ajay , Pratt Lawrence R. , Hoffman Gary G. , Chaudhari Mangesh I. , Rempe Susan B.
Published: May 2018

Electrochemical double‐layer capacitances of charged carbon nanotube (CNT) forests with tetraethyl ammonium tetrafluoro borate electrolyte in propylene carbonate are studied on the basis of molecular dynamics simulation. Direct molecular simulation of the filling of pore spaces of the forest is feasible even with realistic, small CNT spacings. The numerical solution of the Poisson equation based on the extracted average charge densities then yields a regular experimental dependence on the width of the pore spaces, in contrast to the anomalous pattern observed in experiments on other carbon materials and also in simulations on planar slot‐like pores. The capacitances obtained have realistic magnitudes but are insensitive to electric potential differences between the electrodes in this model. This agrees with previous calculations on CNT forest supercapacitors, but not with experiments which have suggested electrochemical doping for these systems. Those phenomena remain for further theory/modeling work.
Towards Hydrogen Storage through an Efficient Ruthenium‐Catalyzed Dehydrogenation of Formic Acid
Authors: Xin Zhuo , Zhang Jiahui , Sordakis Katerina , Beller Matthias , Du Chen‐Xia , Laurenczy Gabor , Li Yuehui
Published: May 2018

Hydrogen is of fundamental importance for the construction of modern clean‐energy supply systems. In this context, the catalytic dehydrogenation of formic acid (FA) is a convenient method to generate H2 gas from an easily available liquid. One of the issues associated with current catalytic dehydrogenation systems is insufficient stability. Here, we present a robust and recyclable system for FA dehydrogenation by combining a ruthenium 1,1,1‐tris(diphenylphosphinomethyl)ethane complex and aluminum trifluoromethanesulfonate (Al(OTf)3). This robust system allows steady H2 production under pressure and recycling for an additional 14 runs without any apparent loss of activity (turnover frequencies up to 1920 h−1, turnover numbers up to 20 000). Notably, the catalyst can also be used for the dehydrogenation of formates and the reverse hydrogenation of bicarbonates and CO2.
Studying the quantity component of seed dispersal effectiveness from exclosure treatments and camera trapping
Authors: Campos Claudia M. , Velez Silvina , Miguel María Florencia , Papú Sofía , Cona Mónica I.
Published: May 2018

The quantity component of effectiveness of seed dispersal by animals is determined by two events: fruit removal (intensity of the interaction) and animal visitation to the plant (frequency of interactions). Considering dispersal of Prosopis flexuosa seeds as case study, this work aimed at investigating the strengths and weaknesses of the two methods for assessing the quantity component of seed dispersal effectiveness: exclosures and camera traps. Prosopis fruits were offered for 48 hr. Exclosure treatments were performed using two types of wire‐screen cages, allowing access to ants (“closed exclosure”) and to small mammals up to 100 g (“open to small mammals”), and a treatment without exclosure (“open to all removers”). The camera trapping experiment was carried out using vertically oriented cameras placed at approximately 1.80 m height and focused on the fruits. The cameras were set in “motion detect mode,” taking series of three consecutive photographs. The exclosures largely allowed estimation of fruit removal by size‐based groups of animals, but did not provide information on species identity. In contrast, camera traps were able to identify all visitors to species level and could not only determine the number of visits by each species but also the proportion of visits, which resulted in removal of fruits. Camera trapping allowed discriminating among small mammals playing different roles, without underestimating fruit removal by scatter‐hoarding species. The quality of estimation of the quantity component of seed dispersal is remarkably better when the camera trapping method is applied. Additional information obtained, such as activity patterns of visitors, can contribute to a better understanding of the seed dispersal process.
Consistent pollen nutritional intake drives bumble bee (Bombus impatiens) colony growth and reproduction across different habitats
Authors: Vaudo Anthony D. , Farrell Liam M. , Patch Harland M. , Grozinger Christina M. , Tooker John F.
Published: May 2018

Foraging behavior is a critical adaptation by insects to obtain appropriate nutrients from the environment for development and fitness. Bumble bees (Bombus spp.) form annual colonies which must rapidly increase their worker populations to support rearing reproductive individuals before the end of the season. Therefore, colony growth and reproduction should be dependent on the quality and quantity of pollen resources in the surrounding landscape. Our previous research found that B. impatiens foraging preferences to different plant species were shaped by pollen protein:lipid nutritional ratios (P:L), with foragers preferring pollen species with a ~5:1 P:L ratio. In this study, we placed B. impatiens colonies in three different habitats (forest, forest edge, and valley) to determine whether pollen nutritional quality collected by the colonies differed between areas that may differ in resource abundance and diversity. We found that habitat did not influence the collected pollen nutritional quality, with colonies in all three habitats collecting pollen averaging a 4:1 P:L ratio. Furthermore, there was no difference in the nutritional quality of the pollen collected by colonies that successfully reared reproductives and those that did not. We found however, that “nutritional intake,” calculated as the colony‐level intake rate of nutrient quantities (protein, lipid, and sugar), was strongly related to colony growth and reproductive output. Therefore, we conclude that B. impatiens colony performance is a function of the abundance of nutritionally appropriate floral resources in the surrounding landscape. Because we did not comprehensively evaluate the nutrition provided by the plant communities in each habitat, it remains to be determined how B. impatiens polylectic foraging strategies helps them select among the available pollen nutritional landscape in a variety of plant communities to obtain a balance of key macronutrients.