bluuebunny/crossref_metadata_2025 huggingface dataset:
French Revolutionary Theater
Authors: Green Christina Suszynski
Published: September 2017

In the early to mid‐eighteenth century, theater was an integral part of the French urbanite's life, as tickets were affordable for most economic classes, and the theater house was considered a nexus for social gathering, gossip, political discourse, and romantic intrigue. The audience was as much a part of the performance as the actors on the stage: the lights were always up, talking was commonplace, spectators mingled with actors on the stage, and opinions were not reserved for the end of the show. In fact, the parterre section of the auditorium (all‐male standing room on the main floor) was renowned for the rowdiness of its patrons. Many attempts were made to silence the theater throughout the second half of the eighteenth century with armed gunmen, dimmed lights, seating in the parterre, and the removal of seating closest to or on the stage, but the spirit of individual rights that was sweeping over France was felt as strongly in the theater as in the circulating political pamphlets demanding the representation of the people before the king. Attempts to silence audiences were thus analogous to attempts to silence the will of the people, and the parterre became a soapbox for the resistance of passivity.
G8 Protests,
G
enoa, 2001
Authors: Azzellini Dario
Published: September 2017

The protests against the G8 (Group of Eight, most industrialized nations) summit in Genoa, Italy, from July 19–21, 2001, was a highpoint in the history of the “alter‐globalization movement.” On July 21, after months of mobilizing across Europe, around 300,000 people took part in one of the largest “movement of movements” demonstrations in the world to date. At the same time, the police unleashed violence of a dimension unknown in Western Europe in the previous two decades, shooting dead the young Carlo Giuliani.
G8 Protests, Gleneagles, 2005
Authors: Dowling Emma
Published: September 2017

The G8 summit is an annual meeting of the Group of Eight most industrialized nations (France, Germany, Italy, Japan, Canada, the UK, the United States and, since 1998, Russia). It is designed to help form a consensus around issues of mutual political and economic importance. The 2005 G8 summit in Scotland, however, was met by protest networks active within the global justice movement who had organized a number of activities to draw attention to the responsibility of the G8 for continued poverty, exploitation, and environmental destruction across the globe.
Gandhi, Mohandas Karamchand (1869–1948)
Authors: Chattopadhyay Kunal
Published: September 2017

Mohandas Karamchand (Mahatma) Gandhi was a foremost Indian nationalist and considered by many as the founder of modern non‐violent resistance. Born in Porbandar, Gujarat State in 1869, Gandhi was married to Kasturbai when he was 13 and she slightly younger, an experience that turned him into a bitter opponent of child marriage. Gandhi left for England in 1888 to study law, after which he went to South Africa in search of a job. In 1907, fighting against a Transvaal law imposing the compulsory registration and fingerprinting of Indians, Gandhi developed a unique non‐violent method of agitation known assatyagraha. This non‐violent form of protest involved the peaceful violation of specific laws, courting mass arrests, occasionalhartals(a form of general strike or closing shops and markets), and spectacular rallies. The protest was followed by anothersatyagrahaof Indian women and miners against the imposition of a poll tax, refusal to recognize Indian marriages, immigration regulations, and indentured labor. In 21 years in South Africa, Gandhi's ideas were formulated, inspired by Ruskin, Tolstoy, and Thoreau. Motivated by Ruskin, Gandhi lived an austere life in a commune, first in Phoenix Farm in Natal, and then in Tolstoy Farm just outside Johannesburg. During this period certain experiments involving diet, childrearing, nature cure, and his personal and professional life convinced Gandhi that a political leader must also be morally pure.
Garvey, Marcus (1887–1940) and Garveyism
Authors: Amador Ernest A.
Published: September 2017

Marcus Garvey, the son of a modest Jamaican family, used his skills as a charismatic orator, gifted journalist, inventive entrepreneur, and political advocate to pioneer the first global black movement, a “back‐to‐Africa” campaign, known as Garveyism. The movement enraptured millions and influenced future black activists and organizations for generations.
German Communist Party, Workers and the Founding of, 1918–1920
Authors: LaPorte Norman
Published: September 2017

The German Communist Party (KPD) was founded during the German Revolution of 1918–19. At this time, German communists played only a peripheral role in the revolution and the council movement that revolutionaries expected would supplant the “bourgeois state.” Even so the conflicts in German society that laid the basis for the first mass‐based communist movement outside of Soviet Russia were already taking shape and the dilemmas facing German communism at this time became recurring themes through the party's development under the Weimar Republic.
German Democratic Republic Protests, 1945–1989
Authors: O'Sullivan Michael E.
Published: September 2017

During the Cold War, the German Democratic Republic (GDR) gained a reputation as the most successful and stable communist state in Eastern Europe. It experienced less unrest and better economic results than its neighbors in Poland, Hungary, and Czechoslovakia. This apparent tranquility made the revolutionary events of 1989 especially surprising. Previously silent East Germans demonstrated until the ruling communists granted them the freedom to travel and voted for unity with their western neighbors. Heated debates have ensued to explain both this long history of stability in the GDR and the sudden upheaval of 1989.
German Nationalism and Workers' Movements, 19th Century
Authors: Bluemel Helen
Published: September 2017

The long nineteenth century, which lasted from the French Revolution of 1789 to World War I (1914–18), marked a period of great change for Germany. The French Revolution led to a new consideration of self in the German nation. The French claim for freedom, equality, and fraternity inspired the German people. It resulted in the realization that, despite the rivalry of sectionalism, there was an overarching cultural and historical connection. The rough road from small individual kingdoms to a united German Reich also conditioned the expression that nationalism found after the 1871 unification of the Reich and its progression until the eve of war in 1914. The 1800s were the century when Germany underwent its industrial revolution, and despite a late start, became a world economic leader. It was the century when workers became the “proletariat,” and when this new social stratum grew conscious of its position in society and established workers' movements.
German Peasant Rebellion, 1525
Authors: De Santiago Ramos Simone Cezanne
Published: September 2017

The Peasant War of 1524–5 was an uprising of several hundred thousand peasants, workers, and artisans in mostly southern Germany but also in Tyrol, Alsace and Lorraine, as well as Carniola, Slovenia. The war, brought on by a combination of several factors, including changes in social and economic structures, heavy taxation by both the nobility and Catholic Church, religious changes engendered by the Reformation, and a crisis of the old feudal system, is often seen as the last medieval peasant revolt in Europe. Marxists, however, interpret it as the first modern revolution.
German Reformation
Authors: Ostoyich Kevin
Published: September 2017

On the night of October 31, 1517, an Augustinian monk and university professor named Martin Luther (1483–1546) nailed his “Ninety‐Five Theses on Indulgences” on the door of the Castle Church in Wittenberg. This cataclysmic event heralded the German Reformation, a movement that spread throughout the Christian world.
G
ermany, Green Movement
Authors: Trump Eric F.
Published: September 2017

The German Green movement flourished as part of the post‐materialist political agitation of the 1960s German left and student protest movements. The Green Party, officially founded in 1980 and today formally known as Bündnis 90/Die Grünen (Alliance 90/The Greens), is the most politically successful Green party in the world. A product of complex ideological strains, its core members were devoted to integrating ecological and socialist politics. Though early Greens wanted to transcend partisan categories, some theorists argue they simply reconstructed Marxian socialism. From the start Greens aimed to give voice to members of marginalized groups, such as gays and lesbians, radical ecologists and women's rights activists. From 1998 to 2005 as junior partner in a coalition with the Social Democratic Party (SPD), the party was lodged between protest and power, testing its dedication to its founding principles.
Germany, Red Army Faction (Baader‐Meinhof Group)
Authors: Vetruba Brian
Published: September 2017

Through three decades and 53 major terrorist acts against the West German state, the left‐extremist Rote Armee Fraktion (Red Army Faction) (RAF) became one of the most violent and persistent terrorist groups in Western Europe. The RAF grew out of the Außerparlamentarische Opposition (Extraparliamentary Opposition) (APO) and the Sozialistischer Deutscher Studentenbund (Socialist German Student Union) (SDS), two of the main groups of the New Left in West Germany protesting against the Vietnam War, proposed curtailment of citizen rights during national crises, and the conspicuous silence on Germany's Nazi past.
Germany, Resistance to Nazism
Authors: Schmidt Ingo
Published: September 2017

Resistance to Nazism began during the Weimar Republic in an effort to contain the Nazi movement and stop its rise to power. Once Hitler was appointed as chancellor and the Nazis transformed representative democracy into a terrorist dictatorship, resistance took various forms ranging from attempts to organize mass action and topple the government to sabotage and absenteeism in the production process and cultural non‐conformity. While direct efforts to overthrow the regime obviously failed, the role of passive forms of resistance and opposition to the Nazis is still controversial. There is also debate about the impact of all kinds of resistance on the shape of postwar Germany after the military defeat of the Nazi regime.
G
ermany, Socialism and Nationalism
Authors: Cox John M.
Published: September 2017

Led by Adolf Hitler, the National Socialist, or Nazi, Party took power in Germany in January 1933, promising a “thousand‐year empire.” Twelve years later, Germany and most of Europe lay in ruins, German Nazism having been subdued by the armies of the Soviet Union and the Western Allies, led by the United States and Britain. But while outside forces were required to bring down Hitler's tyranny, the Nazi dictatorship was never free from domestic opposition. The Third Reich, as the Nazi government was called, found its most persistent and numerous enemies in the remnants of Germany's left‐wing parties, which Hitler had ruthlessly suppressed upon taking power. Although many thousands of German workers and socialists undertook anti‐Nazi resistance activity, their story has been overshadowed, in Germany and elsewhere, by an attempt on Hitler's life organized by opponents within the military elite in July 1944. This conservative military resistance is often inaccurately designated
the
German resistance. However, the resistance of Germany's socialists and communists began in the first days of the dictatorship and only ended with its defeat.
Giovannitti, Arturo (1884–1959)
Authors: Whelehan Niall
Published: September 2017

Arturo Giovannitti was an Italian‐born syndicalist and poet who became politically active at a young age in his hometown of Ripabottoni, in the Molise region of south‐central Italy. In order to curtail his activism, Giovannitti's well‐to‐do family sent him to North America in 1901, where he studied theology in Montreal and New York. Firsthand experience of the hardships of immigrant life led him to abandon Protestantism and, by 1908, he had become a
sovversivo
and member of the Federazione Socialista Italiana del Nord America (FSI). Within three years he was secretary of the FSI and editor of its weekly organ,
Il Proletario
. Aside from journalism, Giovannitti quickly developed a reputation as a charismatic and powerful orator.
Global Day of Action Against the IMF and World Bank, Prague, September 26 (S26), 2000
Authors: Hladík Radim , Mozen Chelsea
Published: September 2017

The protests against the International Monetary Fund (IMF) and World Bank in Prague, Czech Republic, in September 2000 were a pivotal moment in the history of the post‐socialist Czech Republic's alter‐globalization movement. As an expression of radical politics in an era of relative social peace and political stability, following the so‐called Velvet Revolution of 1989, the protests left a deeper imprint on Czech collective memory than have other ad hoc, single issue, or trade union mobilizations. The principal day of protest, September 26, became known as simply S26 and was called for as a Global Day of Action against the IMF and World Bank by the Peoples' Global Action (PGA) network.
Global Justice Movement and Resistance
Authors: Trott Ben
Published: September 2017

The protests against the World Trade Organization (WTO) ministerial in Seattle, 1999, brought the growing global movement against neoliberalism into mainstream consciousness worldwide. It has since manifested itself in numerous mobilizations against political and economic summits, from Quebec, to Prague, Cancun and Hong Kong; given birth to the World Social Forum in Porto Alegre; and taken to the streets against the global “war on terror.” Having contributed to the rupturing of the neoliberal project at the beginning of the twenty‐first century, however, the movement for a different kind of globalization (“counter‐globalization movement” hereafter) is also presented by a number of serious challenges.
Godwin, William (1756–1836)
Authors: de Waard Marco
Published: September 2017

William Godwin's works of philosophy, history, and fiction were instrumental in the formation of modern anarchist thought. Writing in Britain in the aftermath of the French Revolution, and in a climate of hardening reaction, he developed a critique of government and a utopian philosophy of justice which made social and moral progress dependent on the increase of philosophical understanding and the free, unshackled exercise of private judgment.
Gonne, Maud (1866–1953)
Authors: Ruppert Kathleen
Published: September 2017

Edith Maud Gonne was an Irish revolutionary, feminist, and actress. Of Anglo‐Irish descent, she actively promoted the cause of Irish nationalism and other social causes throughout Europe, particularly in France and America. Gonne also founded Inghinidhe na hEireann (Daughters of Erin), an Irish nationalist organization for women.
González Prada, Manuel (1844–1918)
Authors: Roldan‐Figueroa Rady
Published: September 2017

Remembered by his many essays and poetry, the libertarian González Prada has inspired generations of Peruvian intellectuals and politicians. His first significant foray into national public life was in 1886 with the creation of the Literary Circle, a civic and literary body that by 1891 had fully evolved into the political party known as National Union. His collection of essays,
Free Pages
(
Páginas libres
, 1894), stands as a landmark work in his career.
Free Pages
is still imbued with classic liberal ideas, but it already betrays his marked anti‐clericalism. His other major work is
Hours of Battle
(
Horas de lucha
, 1908). González Prada articulated his anarchist ideas in a series of short essays published in the early 1900s. He became an ardent advocate of the indigenous peoples of Peru, and rejected the Peruvian party system. In his writings he also articulated a stern criticism of militarism, defended the free movement of migrants across national borders, and retained an admiration for primitive Christianity. He was the intellectual mentor of the Marxist critic José Carlos Mariátegui and the reformist Victor Raul Haya de la Torre, founder of the American Popular Revolutionary Alliance (1924).
G
orbachev,
M
ikhail (b. 1931)
Authors: Perry Luke
Published: September 2017

Mikhail Gorbachev rose from meager beginnings to become one of the most powerful figures in an international system dominated by the Cold War. A pivotal figure in domestic and international politics, Gorbachev's legacy will be debated for decades; however, there is no denying his significance in the course of Russian history and the end of the Cold War.
Gordon “No Popery” Riots, Britain, 1780
Authors: Haydon Colin
Published: September 2017

The Gordon Riots, which resulted from anti‐Catholic tensions, were some of the most serious riots in eighteenth‐century England. In 1778 Parliament passed the first Catholic Relief Act, curtailing various provisions of the persecuting English penal code. Soon afterwards, a Protestant Association, demanding the measure's repeal, was founded under the leadership of Lord George Gordon (1751–93), an eccentric MP from a Scottish noble family. Petitions for the Relief Act's repeal were raised in London and the English provinces. In Scotland petitions inveighed against a proposed relief bill for that country; and, early in 1779, rioting in Edinburgh and Glasgow ensured the abandonment of the planned legislation.
Gori, Pietro (1865–1911)
Authors: Bertolucci Franco
Published: September 2017

Pietro Gori was born in Messina, Italy on August 14, 1865. He was a lawyer, writer, and poet, but above all he was one of the most important leaders of Italian and international anarchism from the end of the nineteenth century to the beginning of the twentieth. While studying in Pisa, he became an anarchist and wrote political pamphlets, one of which, “Pensieri ribelli” (Rebel Thoughts) (1889), became famous because of his subsequent arrest and trial. On May 1, 1890, after a demonstration of workers in Livorno, Gori and other students and workers were arrested. He was sent to the prisons of Livorno and Lucca, finally being released in 1890. In 1891, he took part in the congress to create the Revolutionary Anarchist Socialist Party, along with other anarchist leaders such as Errico Malatesta. In December the same year, he founded the magazine
L‘Amico del popolo
(The People's Friend), which was forced to close after six issues. Gori wrote for many anarchist magazines and translated the Communist Party manifesto. He also published poetry in
Prigioni e battaglie
(Prisons and Battles). During a conference in 1892, he expounded anarchism's critical position regarding authoritarian socialism. During a national congress the same year, he defended, along with Galleani, the anti‐parliament faction's intransigent position against reformist socialists. He was expelled with Cipriani from the congress of the Socialist International. On July 8, 1894, a few days before the approval of Crispi's laws against anarchists, Gori went to Lugano, escaping the libelous theory that linked him with the outrage of Caserio against the French president, Carnot.
Gramsci, Antonio (1891–1937)
Authors: Le Blanc Paul
Published: September 2017

Antonio Gramsci was the foremost revolutionary Marxist theorist of the Communist Party of Italy, of which he was a founder, and an insightful critic of society, culture, and politics whose influence can be found among an incredibly large number of theorists, intellectuals, and activists both internationally and across the political spectrum.
Greece, Partisan Resistance
Authors: Skalidakis Giannis (Jean‐Marie) , Giovanopoulos Christos
Published: September 2017

Greece was occupied by the Wehrmacht in April 1941 during the German campaign in the Balkans. Before the occupation, the Greek army had fought successfully against Italian aggression in the autumn of 1940. After Greece's defeat, the country was divided into three zones of occupation: Italian (the largest zone), German, and Bulgarian. The government and King George II fled the country along with the British troops after the latter's defeat in the battle of Crete (May 1941). A new collaborationist government with General Georgios Tsolakoglou as prime minister was installed by the forces of occupation.
G
reece, Socialism, Communism, and the Left, 1850–1974
Authors: Margaritis George
Published: September 2017

Throughout the nineteenth century Greece remained a small country with a population of approximately 750,000; geographically it comprised Peloponnesus, the Cyclades islands, and the hinterland of Athens reaching up to the Lamia region in the north. The annexing of the Ionian islands in 1864 and of the Thessaly region in 1881 did not alter the overall picture significantly: the majority of Greeks lived outside the country's contemporary borders up until 1912. The main centers of what might be called a Greek bourgeois class were to be found in Constantinople, Smyrna, Alexandria in Egypt, in the Russian coast cities on the Black Sea, or elsewhere around the East Mediterranean basin.
Greencorn Rebellion,Oklahoma, 1917
Authors: Trumpbour John
Published: September 2017

An uprising against military conscription in World War I, the Greencorn Rebellion mobilized a social base of eastern Oklahoma tenant farmers including whites, African Americans, and Native Americans against US intervention in Europe and wider economic injustice. Centered in Seminole, Hughes, and Pontotoc counties during early August 1917, this rebellion led to the cutting of telegraph lines, destruction of bridges, and wider mayhem, provoking the authorities to round up over 450 people in the sparsely populated region. In total, 184 people received indictments, with 150 found guilty.
G
reenpeace
Authors: Simmons Terry
Published: September 2017

Greenpeace is a household name associated with dramatic efforts to save whales and harp seals from commercial exploitation and to stop nuclear testing in Alaska and French Polynesia. Known around the world for its aggressive environmental advocacy, non‐violent direct action, and clever, media‐savvy events, Greenpeace International has organizations in 42 countries in Europe, the Americas, Asia, and the Pacific. Headquartered in Amsterdam, it has about 2.8 million supporters worldwide, and describes its actions as “bearing witness in a non‐violent manner.” In short, Greenpeace is the manifestation of the common elements and concerns of the environmental movement and the peace movement.
Sonographic Accuracy as a Novel Tool for Point‐of‐care Ultrasound Competency Assessment
Authors: Bell Colin R. , McKaigney Conor J. , Holden Matthew , Fichtinger Gabor , Rang Louise
Published: September 2017

Objectives

The Focused Assessment with Sonography in Trauma (FAST) is a point‐of‐care ultrasound (PoCUS) study that is routine in trauma patient assessment. Many organizations have published training guidelines, which grant competency through the completion of a fixed number of observed scans. This approach is incongruent with current trends in competency‐based medical education. We aim to objectively quantify probe motion and user accuracy to differentiate groups of PoCUS operators.

Methods

Emergency medicine residents were recruited in two groups. The novice group (n = 15) had limited PoCUS experience, whereas the intermediate group (n = 14) had completed at least 50 supervised FAST examinations. Both groups underwent assessment on a live human model. Residents from the novice group returned (n = 9) after completing a curriculum and repeated the assessment using the identical experimental construct.

Results

Significant differences (p < 0.05) were found between the novice and both the intermediate and the novice returned groups in time, path length, and points of interest (POIs) scanned. Novices required more time to complete the full examination (290.82 seconds vs. 197.41 seconds vs. 271.79 seconds), utilized more motion (9392.07 mm vs. 4052.73 mm vs. 4985.05 mm), and imaged fewer POIs (48.13% vs. 95.00% vs. 100.00%) when compared to intermediates and returning novices, respectively. No difference was found between the intermediate and novice returned groups for the complete examination. Spearman's correlation was calculated between variables within each group. Correlations between time and path length were statistically significant (p < 0.05) with novice, intermediate, and novice returned values of 0.67, 0.65, and 0.90. Interestingly, neither time nor path length consistently correlated with POIs scanned in any group.

Conclusion

Differences in probe motion efficiency and POIs scanned between novices and intermediate or returning novice users show promise for use as a quantitative objective assessment tool. Unlike in surgical literature, accuracy did not correlate with path length or time to examination completion.
Highly Luminescent Pincer Gold(III) Aryl Emitters: Thermally Activated Delayed Fluorescence and Solution‐Processed OLEDs
Authors: To Wai‐Pong , Zhou Dongling , Tong Glenna So Ming , Cheng Gang , Yang Chen , Che Chi‐Ming
Published: September 2017

Herein are described the synthesis, photophysical properties and applications of a series of luminescent cyclometalated AuIII complexes having an auxiliary aryl ligand. These complexes show photoluminescence with emission quantum yields of up to 0.79 in solution and 0.84 in thin films (4 wt % in PMMA) at room temperature, both of which are the highest reported values among AuIII complexes. Thermally activated delayed fluorescence (TADF) is the emission origin for some of these complexes. Solution‐processed OLEDs made with these complexes showed sky‐blue to green electroluminescence with external quantum efficiencies (EQEs) of up to 23.8 %, current efficiencies of up to 70.4 cd A−1, and roll‐off of down to 1 %, highlighting the bright prospect of AuIII‐TADF emitters in OLEDs.
Thermal stability of end‐capped and linear sulfonated polyimides, sulfonated polystyrene, and Nafion 117
Authors: Gong Chenliang , Pinatti Laura , Lavigne Gary , Shaw Montgomery T. , Scola Daniel A.
Published: September 2017

The thermal stability of end‐caped and linear sulfonated polyimides (SPIs), sulfonated polystyrene (SPS), and a sulfonated perfluorinated hydrocarbon, Nafion 117, and the corresponding triethylammonium sulfonate salts was investigated by dynamic and isothermal thermogravimetric analysis (TGA). Gas chromatographic‐mass spectrographic analysis (GC/MS) of the sulfonated polymers and the salts to determine the volatiles released from acid and salt groups over a temperature range 200–275 °C was also investigated. GC/MS analysis reveals that water and sulfur dioxide volatiles are released from the sulfonic acids and water, sulfur dioxide and triethyl amine are released from the sulfonate salts. Dynamic and isothermal TGA studies based on weight loss revealed that the SPIs exhibited superior thermal stability than SPS and Nafion 117 sulfonic acids. However, dynamic TGA curves to determine the onset decomposition temperature of the sulfonic acid group reveal that Nafion 117 and SPS sulfonic acids exhibited greater thermal stabilities than the SPIs. The mechanisms of sulfonic acid and triethylammonium sulfonate salt decompositions based on GC/MS, 13C‐NMR, and dynamic TGA curves are proposed. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45694.
Discovering story chains: A framework based on zigzagged search and news actors
Authors: Toraman Cagri , Can Fazli
Published: September 2017

A story chain is a set of related news articles that reveal how different events are connected. This study presents a framework for discovering story chains, given an input document, in a text collection. The framework has 3 complementary parts that i) scan the collection, ii) measure the similarity between chain‐member candidates and the chain, and iii) measure similarity among news articles. For scanning, we apply a novel text‐mining method that uses a zigzagged search that reinvestigates past documents based on the updated chain. We also utilize social networks of news actors to reveal connections among news articles. We conduct 2 user studies in terms of 4 effectiveness measures—relevance, coverage, coherence, and ability to disclose relations. The first user study compares several versions of the framework, by varying parameters, to set a guideline for use. The second compares the framework with 3 baselines. The results show that our method provides statistically significant improvement in effectiveness in 61% of pairwise comparisons, with medium or large effect size; in the remainder, none of the baselines significantly outperforms our method.
Impact of enzalutamide and its main metabolite N‐desmethyl enzalutamide on pharmacokinetically important drug metabolizing enzymes and drug transporters
Authors: Weiss Johanna , Kocher Jutta , Mueller Corina , Rosenzweig Stephanie , Theile Dirk
Published: September 2017

Enzalutamide is a new drug against castration‐resistant prostate cancer. Recent data indicate profound induction of drug metabolizing enzymes (e.g. cytochrome P450 isoenzyme (CYP) 3A4) but comprehensive in vitro data on other CYP enzymes, drug conjugating enzymes or drug transporters is scarce. Moreover, the mechanisms of induction are poorly investigated and the effects of the active metabolite N‐desmethyl enzalutamide are unknown. Using LS180 cells as an induction model and quantitative real‐time reverse transcription polymerase chain reaction, our study demonstrated a concentration‐dependent induction of CYP1A1, CYP1A2, CYP3A5, CYP3A4, UGT1A3, UGT1A9, ABCB1, ABCC2 and ABCG2 mRNA. Induction of CYP3A4 and ABCB1 was confirmed by Western blot analysis and is likely mediated by activation of the nuclear receptor pregnane x receptor, elucidated by a luciferase‐based reporter gene assay. Enzalutamide's main active metabolite N‐desmethyl enzalutamide exhibited only weak induction properties. mRNA expression of UGT2B7 was suppressed by enzalutamide and its metabolite. Both compounds are apparently not transported by P‐glycoprotein (P‐gp) or breast cancer resistance protein (BCRP). N‐desmethyl enzalutamide more potently inhibited important drug transporters (P‐gp, BCRP, OATPs) than enzalutamide. Taken together, the pharmacokinetics of concurrently administered drugs is likely altered during enzalutamide therapy. Levels of metabolically (mainly CYP3A4) eliminated drugs are expected to be decreased, whereas the abundance of compounds with solely transporter‐determined pharmacokinetics (P‐gp, OATPs) is likely enhanced.
Growth Rate Changes in CHO Host Cells Are Associated with Karyotypic Heterogeneity
Authors: Baik Jong Youn , Lee Kelvin H.
Published: September 2017

Chinese hamster ovary (CHO) cell line instability and clonality issues can affect cell culture phenotypes such as cell growth, productivity, or product quality and remain challenges for biopharmaceutical manufacturing. While there have been efforts for characterizing cell line instability in CHO production cell lines, a pre‐existing level of cell line instability in CHO host cells has not been determined. In this study, cell line instability and chromosomal heterogeneity of the host, CHO‐DUK cell line, is reported by using a karyotyping approach. Long‐term cultures and karyotype analysis of CHO‐DUK cells revealed that the growth rate was higher in later passage cultures, correlating with an increase in the population ratio containing the mar3 chromosome. To further investigate a correlation between growth rate and karyotype, CHO‐DUK cells are subcloned by limiting dilution and the growth rate and karyotype of each subclone are determined. Subclones containing the mar3 chromosome exhibit higher cell growth rates than subclones without the mar3 chromosome. Finally, karyotype analysis indicate that CHO‐DUK cells, as well as limiting‐diluted subclones, exhibit a karyotypically heterogeneous population, suggesting that chromosomal rearrangements occur spontaneously and frequently even in non‐engineered host cells. These results demonstrate CHO host cell line instability and suggest that chromosomal instability and karyotypic changes are associated with compromised clonality (heterogeneity), affecting cell line (in)stability in CHO host cells.
Human Pulmonary 3D Models For Translational Research
Authors: Zscheppang Katja , Berg Johanna , Hedtrich Sarah , Verheyen Leonie , Wagner Darcy E. , Suttorp Norbert , Hippenstiel Stefan , Hocke Andreas C.
Published: September 2017

Lung diseases belong to the major causes of death worldwide. Recent innovative methodological developments now allow more and more for the use of primary human tissue and cells to model such diseases. In this regard, the review covers bronchial air‐liquid interface cultures, precision cut lung slices as well as ex vivo cultures of explanted peripheral lung tissue and de‐/re‐cellularization models. Diseases such as asthma or infections are discussed and an outlook on further areas for development is given. Overall, the progress in ex vivo modeling by using primary human material could make translational research activities more efficient by simultaneously fostering the mechanistic understanding of human lung diseases while reducing animal usage in biomedical research.
A Cost‐Effective Culture System for the In Vitro Assembly, Maturation, and Stimulation of Advanced Multilayered Multiculture Tubular Tissue Models
Authors: Loy Caroline , Pezzoli Daniele , Candiani Gabriele , Mantovani Diego
Published: September 2017

The development of tubular engineered tissues is a challenging research area aiming to provide tissue substitutes but also in vitro models to test drugs, medical devices, and even to study physiological and pathological processes. In this work, the design, fabrication, and validation of an original cost‐effective tubular multilayered‐tissue culture system (TMCS) are reported. By exploiting cellularized collagen gel as scaffold, a simple moulding technique and an endothelialization step on a rotating system, TMCS allowed to easily prepare in 48 h, trilayered arterial wall models with finely organized cellular composition and to mature them for 2 weeks without any need of manipulation. Multilayered constructs incorporating different combinations of vascular cells are compared in terms of cell organization and viscoelastic mechanical properties demonstrating that cells always progressively aligned parallel to the longitudinal direction. Also, fibroblast compacted less the collagen matrix and appeared crucial in term of maturation/deposition of elastic extracellular matrix. Preliminary studies under shear stress stimulation upon connection with a flow bioreactor are successfully conducted without damaging the endothelial monolayer. Altogether, the TMCS herein developed, thanks to its versatility and multiple functionalities, holds great promise for vascular tissue engineering applications, but also for other tubular tissues such as trachea or oesophagus.
Development of a general defined medium for Pichia pastoris
Authors: Matthews Catherine B. , Kuo Angel , Love Kerry R. , Love J. Christopher
Published: September 2017

Pichia pastoris is widely used as a host for recombinant protein production. More than 500 proteins have been expressed in the organism at a variety of cultivation scales, from small shake flasks to large bioreactors. Large‐scale fermentation strategies typically employ chemically defined growth medium because of its greater batch‐to‐batch consistency and in many cases, lower costs compared to complex medium. For biopharmaceuticals, defined growth medium may also simplify downstream purification and regulatory documentation. Standard formulations of defined media for P. pastoris are minimal ones that lack the metabolic intermediates provided by complex components such as peptone and yeast extract. As a result, growth rates and per‐cell productivities are significantly lower than in complex medium. We have designed a rich defined medium (RDM) for Pichia pastoris by systematically evaluating nutrients of increasing complexity and identifying those that are most critical for growth. We have also employed transcriptomics to gain deeper insights into the underlying metabolic processes and inform our media design. We have demonstrated that using RDM for expression of three heterologous proteins yields titers comparable to, or higher than, those in standard complex medium. RDM improves productivity of P. pastoris fermentations and its development demonstrates the usefulness of transcriptomics to accelerate process development for new molecules.
Countercurrent staged diafiltration for formulation of high value proteins
Authors: Nambiar Anirudh M. K. , Li Ying , Zydney Andrew L.
Published: September 2017

A number of groups have studied the application of continuous bioreactors and continuous chromatographic systems as part of efforts to develop an integrated continuous biomanufacturing process. The objective of this study was to examine the feasibility of using a countercurrent staged diafiltration process for continuous protein formulation with reduced buffer requirements. Experiments were performed using a polyclonal immunoglobulin (IgG) with Cadence™ Inline Concentrators. Model equations were developed for the product yield, impurity removal, and buffer requirements as a function of the number of stages and the stage conversion (ratio of permeate to feed flow rate). Data from a countercurrent two‐stage system were in excellent agreement with model calculations, demonstrating the potential of using countercurrent staged diafiltration for protein formulation. Model simulations demonstrated the importance of the countercurrent staging on both the extent of buffer exchange and the amount of buffer required per kg of formulated product. The staged diafiltration process not only provides for continuous buffer exchange, it could also provide significant reductions in the number of pump passes while providing opportunities for reduced buffer requirements.
Dry biorefining maximizes the potentials of simultaneous saccharification and co‐fermentation for cellulosic ethanol production
Authors: Liu Gang , Zhang Qiang , Li Hongxing , Qureshi Abdul S. , Zhang Jian , Bao Xiaoming , Bao Jie
Published: September 2017

Despite the well‐recognized merits of simultaneous saccharification and co‐fermentation (SSCF) on relieving sugar product inhibition on cellulase activity, a practical concomitance difficulty of xylose with inhibitors in the pretreated lignocellulose feedstock prohibits the essential application of SSCF for cellulosic ethanol fermentation. To maximize the SSCF potentials for cellulosic ethanol production, a dry biorefining approach was proposed starting from dry acid pretreatment, disk milling, and biodetoxification of lignocellulose feedstock. The successful SSCF of the inhibitor free and xylose conserved lignocellulose feedstock after dry biorefining reached a record high ethanol titer at moderate cellulase usage and minimum wastewater generation. For wheat straw, 101.4 g/L of ethanol (equivalent to 12.8% in volumetric percentage) was produced with the overall yield of 74.8% from cellulose and xylose, in which the xylose conversion was 73.9%, at the moderate cellulase usage of 15 mg protein per gram cellulose. For corn stover, 85.1 g/L of ethanol (equivalent to 10.8% in volumetric percentage) is produced with the overall conversion of 84.7% from cellulose and xylose, in which the xylose conversion was 87.7%, at the minimum cellulase usage of 10 mg protein per gram cellulose. Most significantly, the SSCF operation achieved the high conversion efficiency by generating the minimum amount of wastewater. Both the fermentation efficiency and the wastewater generation in the current dry biorefining for cellulosic ethanol production are very close to that of corn ethanol production, indicating that the technical gap between cellulosic ethanol and corn ethanol has been gradually filled by the advancing biorefining technology.
Temperature‐dependent dynamic control of the TCA cycle increases volumetric productivity of itaconic acid production by Escherichia coli
Authors: Harder Björn‐Johannes , Bettenbrock Katja , Klamt Steffen
Published: September 2017

Based on the recently constructed Escherichia coli itaconic acid production strain ita23, we aimed to improve the productivity by applying a two‐stage process strategy with decoupled production of biomass and itaconic acid. We constructed a strain ita32 (MG1655 ΔaceA Δpta ΔpykF ΔpykA pCadCs), which, in contrast to ita23, has an active tricarboxylic acid (TCA) cycle and a fast growth rate of 0.52 hr−1 at 37°C, thus representing an ideal phenotype for the first stage, the growth phase. Subsequently we implemented a synthetic genetic control allowing the downregulation of the TCA cycle and thus the switch from growth to itaconic acid production in the second stage. The promoter of the isocitrate dehydrogenase was replaced by the Lambda promoter (pR) and its expression was controlled by the temperature‐sensitive repressor CI857 which is active at lower temperatures (30°C). With glucose as substrate, the respective strain ita36A grew with a fast growth rate at 37°C and switched to production of itaconic acid at 28°C. To study the impact of the process strategy on productivity, we performed one‐stage and two‐stage bioreactor cultivations. The two‐stage process enabled fast formation of biomass resulting in improved peak productivity of 0.86 g/L/hr (+48%) and volumetric productivity of 0.39 g/L/hr (+22%) in comparison to the one‐stage process. With our dynamic production strain, we also resolved the glutamate auxotrophy of ita23 and increased the itaconic acid titer to 47 g/L. The temperature‐dependent activation of gene expression by the Lambda promoters (pR/pL) has been frequently used to improve protein or, in a few cases, metabolite production in two‐stage processes. Here we demonstrate that the system can be as well used in the opposite direction to selectively knock‐down an essential gene (icd) in E. coli to design a two‐stage process for improved volumetric productivity. The control by temperature avoids expensive inducers and has the potential to be generally used to improve cell factory performance.
Power input effects on degeneration in prolonged penicillin chemostat cultures: A systems analysis at flux, residual glucose, metabolite, and transcript levels
Authors: Wang Guan , Wu Baofeng , Zhao Junfei , Haringa Cees , Xia Jianye , Chu Ju , Zhuang Yingping , Zhang Siliang , Heijnen Joseph J. , van Gulik Walter , Deshmukh Amit T. , Noorman Henk J.
Published: September 2017

In the present work, by performing chemostat experiments at 400 and 600 RPM, two typical power inputs representative of industrial penicillin fermentation (P/V, 1.00 kW/m3 in more remote zones and 3.83 kW/m3 in the vicinity of the impellers, respectively) were scaled‐down to bench‐scale bioreactors. It was found that at 400 RPM applied in prolonged glucose‐limited chemostat cultures, the previously reported degeneration of penicillin production using an industrial Penicillium chrysogenum strain was virtually absent. To investigate this, the cellular response was studied at flux (stoichiometry), residual glucose, intracellular metabolite and transcript levels. At 600 RPM, 20% more cell lysis was observed and the increased degeneration of penicillin production was accompanied by a 22% larger ATP gap and an unexpected 20‐fold decrease in the residual glucose concentration (Cs,out). At the same time, the biomass specific glucose consumption rate (qs) did not change but the intracellular glucose concentration was about sixfold higher, which indicates a change to a higher affinity glucose transporter at 600 RPM. In addition, power input differences cause differences in the diffusion rates of glucose and the calculated Batchelor diffusion length scale suggests the presence of a glucose diffusion layer at the glucose transporting parts of the hyphae, which was further substantiated by a simple proposed glucose diffusion‐uptake model. By analysis of calculated mass action ratios (MARs) and energy consumption, it indicated that at 600 RPM glucose sensing and signal transduction in response to the low Cs,out appear to trigger a gluconeogenic type of metabolic flux rearrangement, a futile cycle through the pentose phosphate pathway (PPP) and a declining redox state of the cytosol. In support of the change in glucose transport and degeneration of penicillin production at 600 RPM, the transcript levels of the putative high‐affinity glucose/hexose transporter genes Pc12g02880 and Pc06g01340 increased 3.5‐ and 3.3‐fold, respectively, and those of the pcbC gene encoding isopenicillin N‐synthetase (IPNS) were more than twofold lower in the time range of 100–200 hr of the chemostat cultures. Summarizing, changes at power input have unexpected effects on degeneration and glucose transport, and result in significant metabolic rearrangements. These findings are relevant for the industrial production of penicillin, and other fermentations with filamentous microorganisms.
Comparison of Chemical Profile and Antioxidant Capacity of Seeds and Oils from Salvia sclarea and Salvia officinalis
Authors: Živković Jelena , Ristić Mihailo , Kschonsek Josephine , Westphal Anna , Mihailović Milica , Filipović Vladimir , Böhm Volker
Published: September 2017

Composition of tocopherols, tocotrienols, carotenoids, fatty acids, as well as hydrophilic and lipophilic antioxidant activities, were determined in seeds of two Salvia species and oils obtained from them. Both seeds contained a large amount of oil (around 20%) rich in polyunsaturated fatty acids. While Salvia officinalis seed oil can be classified as oleic‐linoleic oil, the predominant fatty acid in Salvia sclarea was α‐linolenic acid (around 54%). Among tocols, the main isomers in both seeds and oils were γ‐tocopherol, followed by α‐tocopherol. Concerning carotenoids, their concentration was around 0.75 mg/100 g of seeds and 0.16 mg/100 g of oils, with a predominance of lutein. Oil and seeds of S. officinalis exhibited higher antioxidant potential compared to S. sclarea investigated samples which could be attributed to higher content of total vitamin E and carotenoids. This study provides results that enables use of two Salvia species as new alternative sources of vegetable oils.
On the Electronic Origin of Remarkable Ligand Effects on the Reactivities of [NiL]+ Complexes (L=C6H5, C5H4N, CN) towards Methane
Authors: Zhou Shaodong , Firouzbakht Marjan , Schlangen Maria , Kaupp Martin , Schwarz Helmut
Published: September 2017

The gas‐phase reactions of [NiL]+ (L=C6H5, C5H4N, CN) with methane have been explored by using electrospray‐ionization mass spectrometry (ESI‐MS) complemented by quantum chemical calculations. Though the phenyl Ni complex [Ni(C6H5)]+ exclusively abstracts one hydrogen atom from methane at ambient conditions, the cyano Ni complex [Ni(CN)]+ brings about both H‐atom abstraction and ligand exchange to generate [Ni(CH3)]+. In contrast, the complex 2‐pyridinyl Ni [Ni(C5H4N)]+ is inert towards this substrate. The presence of the empty 4s(Ni) orbital dominates the proton‐coupled electron transfer (PCET) processes for the investigated systems.