bluuebunny/crossref_metadata_2025 huggingface dataset:
Kawabata Yasunari: Modernism, Memory, and Desire
Authors: Washburn Dennis
Published: December 2019

Kawabata Yasunari received the Nobel Prize in Literature in 1968 for works that, according to the selection committee, revealed the essence of the Japanese mind. Having long idealized Japan's artistic traditions, Kawabata embraced this judgment. Yet he was more than a parochial literary conservator. Influenced by the global spread of modernist movements, his traditionalism and nationalist aesthetic allowed him to give voice to the spiritual homelessness of modern urban subjects and their desire to return to an authentic Japan. His conservative brand of modernism was proto‐fascist, and he disavowed it after Japan's defeat. The struggle to come to terms with his early career gave his postwar fiction greater moral depth and secured his place in the canon of world literature.
William Faulkner and the World Literature Debate: Is the Radical in Radical Form the Radical in Radical Politics?
Authors: Aboul‐Ela Hosam M.
Published: December 2019

Faulkner's work, reputation, and impact have a particular resonance for questions of literature's relationship to the material world and its agency within it. He at times insisted that he aspired to write for himself rather than an audience, and his fiction uses a style and language that provocatively challenges readers. Still, his work has had special purchase for so many global writers who read English as a second language or who needed to access his work through translations. In their own voices, these global authors consistently yoke both Faulkner's style and his context as the double‐sided base of his importance for them. This productive connection between stylistics and worldliness indicates to the critic of world literatures the necessity of reading global texts both from a distance and from up close.
Lu Xun's Fictional Worlds
Authors: Kaldis Nicholas A.
Published: December 2019

Lu Xun (1881–1936) is considered China's leading literary figure of the modern era. Readers, writers, and intellectuals in China and around the world have been drawn to and inspired by his work for 100 years. Scholars frequently comment on his complex use of irony, his representations of the relationship between modern intellectuals and subalterns, and his conflicted struggle to comprehend, reconcile, and critique both tradition and modernity. Lu Xun was at once a model reader and writer of world literature; when we read his work, we mirror and instantiate the practice of world literature in which he himself was engaged.
The Tale of Genji: Showing and Telling a World
Authors: Kamens Edward
Published: December 2019

Who tells the tale, how, and why? Focusing on two episodes inThe Tale of Genji(and illustrations of them), one with female readers, the other with male storytellers, this chapter explores key features of this core classic text from the eleventh century, including its use of tropes of spirit possession, voyeurism, surrogacy, and the tale‐telling act itself, as well as the ways in which these features are gendered. The chapter also describes some of the modes and means of representation that characterizeThe Taleand the genre of which it is exemplary.
Jorge Isaacs's Diasporic Novel:Maríabetween National and World Literatures
Authors: Martínez‐Pinzón Felipe
Published: December 2019

This chapter revisitsMaría(1867) and Jorge Isaacs's biography in the context of the growing discourse amongst and betweennationalnovels andworldliterature. By doing so, the chapter emphasizes how imaginations of the nation are fed and produced in the novel by larger global designs, by histories of forced migration, exile, and diaspora. Reading the novel as the story of several diasporic communities seeking to legitimize themselves as newcomers in Valle del Cauca (the location of the novel),Maríaexpands and complicates literary geographies that tie reading practices to distinct national histories, showing how these are usually embedded in imperial histories.
General Introduction: The Companion to World Literature … For Those Who Yearn
Authors: Seigneurie Ken
Published: December 2019

This General Introduction frames world literature as a “home” for readers in a culturally integrating world. Keeping with this metaphor, the
Wiley Blackwell Companion to World Literature
bids to provide a floor plan and furnishing. This essay sketches the structural outline and rationale for the
Companion
. What are the principles of topic selection? Who is the target readership? What is the relationship between the
Companion
essays and academic scholarship in fields such as national, regional or ethnic literatures? The General Introduction also anticipates some of the objections often leveled at the emerging discipline of World Literature: Does it reduce cultural specificities to neocolonial commodities? Does it seek to supplant disciplines relating to national and Comparative Literature? Without disregarding these objections, this essay stresses the
Companion's
commitment to recognizing and bridging, not denying or emulsifying, cultural differences.
Demosthenes,strategos
Authors: Roisman Joseph
Published: December 2019

Demosthenes, son of Alkisthenes (ca. 460–413bce), was an Athenian general in the Peloponnesian War, famous for his capture of Pylos and subsequent defeat of the Spartans on island of Sphacteria. He died in Sicily after the failure of the Athenian attempt to capture Syracuse.
Dorian tribes
Authors: Jones Nicholas F.
Published: December 2019

“Tribes” is the conventional but misleading rendering of Greekphylai(singular,phyle), the principal units segmenting the populations and/or territories of many, perhaps originally all, city‐states. Just as in the case of the four ancestralphylaiof the Ionians, Dorians inherited a set of threephylai, with an attested historical distribution among the Peloponnesian city‐states and their colonial foundations, on the islands of the southern Aegean, and along the southwestern seaboard of Asia Minor.
Euboulos (Eubulus), Athenian politician
Authors: Harris Edward M.
Published: December 2019

Euboulos was one of the most influential politicians in Athens in the period from the end of the Social War (355
bce
).
Ionian tribes
Authors: Jones Nicholas F.
Published: December 2019

“Tribes” is the conventional but misleading rendering of Greek phylai (singular,phylê), the principal units segmenting the populations and/or territories of many, perhaps originally all, Greek city‐states. Just as in the case of the three ancestralphylaiof the Dorians, Ionians inherited a set of fourphylai, with an attested distribution at Athens and, to the east, on the Ionian islands and along the Ionian seaboard.
Koroneia (Coronea)
Authors: Keim Benjamin
Published: December 2019

Koroneia, a
polis
in western Boiotia, was the site of two Classical battles (447/6
bce
and 394
bce
) as well as a sanctuary of Athena Itonia, site of the Pamboiotian festival and meeting‐place of the Boiotian League.
Thirty Years’ Peace
Authors: Keim Benjamin
Published: December 2019

The Thirty Years' Peace, enacted by Sparta and Athens in 446/5bce, concluded the First Peloponnesian War and shaped Greek interstate relations until the outbreak of the Great Peloponnesian War in 431bce.
Dioiketes
, Ptolemaic Egypt
Authors: Clarysse Willy
Published: December 2019

The
dioiketes
was a financial official. In the Ptolemaic period, there were local
dioiketai
and a
dioiketes
located centrally in Alexandria. It is the latter that is the subject of this entry.
Coinage, Ptolemaic
Authors: Lorber Catharine
Published: December 2019

Three salient features distinguish Ptolemaic coinage from the currency of other Hellenistic kingdoms: a lower weight standard for precious metal coins; an abundance of ostentatious, high‐value gold pieces; and the importance of bronze currency.
Lucian
Authors: García‐Ehrenfeld Claudio
Published: December 2019

Lucian, born ca. 115 or 125 into the local elite at Samosata, in the Roman province of Syria, was a traveling writer of Greek best known for his dialogues and rhetorical showpieces, as well as his uniquely witty blend of literary knowledge, philosophy, and satire.
Gynaikonomos
Authors: Stavrianopoulou Eftychia
Published: December 2019

Gynaikonomoi were officials who exercised supervisory functions on female public conduct.
Leonidas of Tarentum
Authors: Gutzwiller Kathryn
Published: December 2019

Leonidas of Tarentum (first half of the third century
bce
) was one of the major Hellenistic epigrammatists. Attributed to him are 103 epigrams, mostly in elegiac meter.
Lycophron
Authors: Hurst André
Published: December 2019

Lycophron of Chalkis (ca. 330 to mid‐third centurybce) is known as a tragic poet, and also as the author of the most obscure of poems: a prophecy of Kassandra by the titleAlexandra.
Seleukos II Kallinikos (Seleucus II Callinicus)
Authors: Heller André
Published: December 2019

Seleukos II Kallinikos ruled the Seleucid Empire from 246 to 225. During his reign, the realm experienced hard times. In the Third Syrian War, Ptolemy III campaigned as far as Babylon and proclaimed the conquest of the whole empire. After the peace agreement with Ptolemy, Seleukos’ brother Antiochos Hierax proclaimed himself king in Asia Minor. As a consequence of this dynastic strife, the Eastern satrapies gained local autonomy.
Evagrius of Pontus
Authors: Simelidis Christos
Published: December 2019

Evagrius (ca. 345–399ce), a monastic writer and calligrapher, was born in Pontus. He accompanied Gregory of Nazianzus to Constantinople and became a preacher there under Gregory and his successor, Nektarios. After a short stay in Palestine, where he met Melania the Elder, he spent the rest of his life (from ca. 383) in the Nitrian desert, where he associated with Makarios of Egypt.
Bakenrenef (Bokkhoris)
Authors: Dodson Aidan
Published: December 2019

Bakenrenef (Bokkhoris), king of Egypt, 24th Egyptian Dynasty, ca. 718–712
bce
.
Limitanei
Authors: Whately Conor
Published: December 2019

Thelimitaneiwere the border troops based on the frontiers of the Roman Empire.
Metaurus, battle of
Authors: Hoyos Dexter
Published: December 2019

The Romans defeated Hannibal's brother Hasdrubal in 208
bce
in northern Italy, after Hasdrubal marched from Spain hoping to reinforce his brother in the south. The victory ensured that the Carthaginians could not win their long war with Rome, and made ultimate defeat virtually inevitable.
Trasimene, battle of
Authors: Hoyos Dexter
Published: December 2019

In June 217
bce,
Hannibal ambushed the Roman army of the consul Gaius Flaminius as it advanced along the northern shore of Lake Trasimene in Etruria (Tuscany). The army was annihilated; the dead included Flaminius. Hannibal was now free to carry forward his invasion of Italy.
Spartacus
Authors: Nice Alex
Published: December 2019

Spartacus (ca. 106–71
bce
) was a Thracian gladiator who led a slave revolt against Rome from 73 to 71
bce
.
Chaldaeans, astrologers
Authors: Greenbaum Dorian Gieseler
Published: December 2019

It was conventional practice in the Greco‐Roman world for astrologers to be called by the generic term “Chaldaeans,” since Mesopotamia was renowned for astral omens and astrology (Chaldaea was in southern Mesopotamia).
Pytheas of Massalia
Authors: Kaplan Philip G.
Published: December 2019

Pytheas (ca. 350–320
bce
) was a geographer, astronomer, and explorer from the Greek city of Massalia. None of his works survive, but he is credited by later writers with making observations on latitudes and solstices, and speculating on the cause of tides. He also gave an account of a journey to the seas north of Europe, and was the first Greek to explore the British Isles. He claimed to have found an island called Thule, possibly Iceland or the coast of Norway. He may have also traveled eastward as far as the Baltic Sea. Some later geographers were skeptical of his discoveries, although modern scholarship has generally accepted them as genuine.
FY 2020 Appropriations: Stimulants added to SOR's $1.5 billion
Authors: Knopf Alison
Published: December 2019

Appropriations bills for FY 2020 released last week detail some good news for the field. In the State Opioid Response (SOR) grants, there would be more flexibility: specifically, these could be used for stimulants.
Influence of Fiber Stiffness on Meniscal Cell Migration into Dense Fibrous Networks
Authors: Song Kwang Hoon , Heo Su‐Jin , Peredo Ana P. , Davidson Matthew D. , Mauck Robert L. , Burdick Jason A.
Published: December 2019

Fibrous scaffolds fabricated via electrospinning are being explored to repair injuries within dense connective tissues. However, there is still much to be understood regarding the appropriate scaffold properties that best support tissue repair. In this study, the influence of the stiffness of electrospun fibers on cell invasion into fibrous scaffolds is investigated. Specifically, soft and stiff electrospun fibrous networks are fabricated from crosslinked methacrylated hyaluronic acid (MeHA), where the stiffness is altered via the extent of MeHA crosslinking. Meniscal fibrochondrocyte (MFC) adhesion and migration into fibrous networks are investigated, where the softer MeHA fibrous networks are easily deformed and densified through cellular tractions and the stiffer MeHA fibrous networks support ≈50% greater MFC invasion over weeks when placed adjacent to meniscal tissue. When the scaffolds are sandwiched between meniscal tissues and implanted subcutaneously, the stiffer MeHA fibrous networks again support enhanced cellular invasion and greater collagen deposition after 4 weeks when compared to the softer MeHA fibrous networks. These results indicate that the mechanics and deformability of fibrous networks likely alter cellular interactions and invasion, providing an important design parameter toward the engineering of scaffolds for tissue repair.
Spatiotemporal Distribution of Agrin after Intrathecal Injection and Its Protective Role in Cerebral Ischemia/Reperfusion Injury
Authors: Li Shiyong , Wang Ye , Jiang Dawei , Ni Dalong , Kutyreff Christopher J. , Barnhart Todd E. , Engle Jonathan W. , Cai Weibo
Published: December 2019

Intrathecal injection, drugs transporting along perivascular spaces, represents an important route for maintaining blood–brain barrier (BBB) integrity after cerebral ischemia/reperfusion (I/R) injury. However, after being directly injected into cerebrospinal fluid (CSF), the temporal and spatial changes in the distribution of therapeutic protein drugs have remained unknown. Here, with positron emission tomography (PET) imaging, the uptake of 89Zr‐agrin is noninvasively and dynamically monitored. These data demonstrate the time–activity curve of drugs in the brain subregions and their spatial distribution in different organs after intrathecal administration. Furthermore, agrin treatment effectively inhibits BBB disruption by reducing the loss of tight‐junctional proteins. Importantly, the infarct volume is reduced; the number of apoptotic neurons is decreased; and neurological function is improved in mouse I/R injury models. Thus, intrathecal injection of agrin provides the basis for a new strategy to research and develop protein drugs for reducing the aggravation of I/R injury.
Deepening of response after completing rituximab‐containing therapy in patients with Waldenstrom macroglobulinemia
Authors: Castillo Jorge J. , Gustine Joshua N. , Keezer Andrew , Meid Kirsten , Flynn Catherine A. , Dubeau Toni E. , Chan Gloria , Chen Jiaji , Demos Maria G. , Guerrera Maria L. , Jimenez Cristina , Kofides Amanda , Liu Xia , Munshi Manit , Tsakmaklis Nicholas , Patterson Christopher J. , Xu Lian , Yang Guang , Hunter Zachary R. , Treon Steven P.
Published: December 2019

Rituximab‐containing regimens are commonly used for frontline therapy in patients with symptomatic Waldenström macroglobulinemia (WM). We had observed that a portion of WM patients experienced deepening of response months to years after therapy completion. We carried a retrospective study aimed at describing this phenomenon. We gathered baseline data, and responses at end of induction, end of maintenance and best response. Deepening of response was defined as ≥25% decrease in serum IgM achieved at a later time from therapy completion. Of 178 patients included, 116 (65%) received maintenance therapy and 62 (35%) were observed. In patients who received maintenance, 44 (38%) had ≥25% decrease in serum IgM level after the end of maintenance with a median time from end of maintenance to lowest IgM level of 1.6 years (range 0.1‐7.9 years). In patients who were observed, 19 (31%) had ≥25% decrease in serum IgM level after the end of induction with a median time from end of induction to lowest IgM level of 1.6 years (range 0.2‐5.1 years). Baseline hemoglobin <11.5 g/dL, bone marrow involvement ≥50%, CXCR4 mutations and serum IgM ≥4000 mg/dL were associated with lower odds of deepening of response after therapy completion. Deepening of response was associated with better progression‐free survival (PFS; HR 0.46, 95% CI 0.26‐0.80; P = .006) and better survival after frontline treatment initiation (SAFTI; HR 0.21, 95% CI 0.06‐0.73; P = .01). In conclusion, deepening of response occurs in one third of WM patients after completing rituximab‐containing regimens and was associated with better PFS and SAFTI.
Does nutrition have an effect on the timing of tooth formation?
Authors: Esan Temitope A. , Schepartz Lynne A.
Published: December 2019

Background

The effect of nutritional status on the timing of permanent tooth formation is not well understood, despite clear evidence that systemic stresses result in enamel defects during tooth formation.

Aim

This study investigated the effect of nutritional status (measured as BMI, height, weight, mid‐upper arm circumference, and head circumference) on permanent tooth formation.

Method

This was a prospective cross‐sectional study involving 642 (270 males, 372 females) healthy Black South African participants aged 5–20 years. The height and BMI were converted to z‐scores using WHO z‐score for age tables. The participants were grouped into underweight/short for age (<−2), normal (≥ − 2 to 2.0) and overweight/obese/tall for age (>2). Panoramic radiographs of the children were assessed using Demirjian's eight stages of permanent tooth formation and age was estimated using Demirjian's method. Probit regression analysis was used to calculate the mean age of attainment of the developmental stages for the left mandibular teeth (I2–M2).

Results

There was significant advancement in the age of attainment of the final (H) stage for the majority of permanent teeth in the overweight (mean male BMI 22.9; female 27.94) group compared to the underweight (p < .05). Negative binomial regression indicated that age, height, and BMI were significant predictors of the dental maturity score for males (p < .05), while age, height, weight, BMI and HC were significant predictors for females (p < .05).

Conclusion

Nutritional status had a significant effect on the timing of tooth formation in males and females in the study population. The effect was mainly noticeable for children in the extremes of the spectrum of BMI z‐scores.
Fortschritte in der optischen Einzelmoleküldetektion: Auf dem Weg zu höchstempfindlichen Bioaffinitätsassays
Authors: Farka Zdeněk , Mickert Matthias J. , Pastucha Matěj , Mikušová Zuzana , Skládal Petr , Gorris Hans H.
Published: December 2019

Die Messung niedrigster Konzentrationen von Analyten und insbesondere von Biomarkern ist von grundlegender Bedeutung, z. B. für die Früherkennung von Krankheiten. Die Aussicht, einzelne Analytmoleküle nachzuweisen und somit die ultimative Nachweisgrenze zu erreichen, treibt die Entwicklung von Einzelmolekül‐Bioaffinitätstests voran. Zwar haben bereits viele Übersichtsartikel mögliche analytische und diagnostische Anwendungen von Einzelmolekültechniken hervorgehoben, diese Techniken bleiben jedoch bisher in Bezug auf Praxistauglichkeit hinter den Erwartungen zurück. Dieser Aufsatz erläutert den theoretischen Hintergrund zu Einzelmolekül‐ oder besser digitalen Assays, um deren Potenzial im Vergleich zu herkömmlichen analogen Assays kritisch zu bewerten, und beschreibt ausgewählte Bioaffinitätstests zum Nachweis von Biomolekülen wie Proteine, Nukleinsäuren und Viren. Die Gliederung des Aufsatzes reflektiert die Vielseitigkeit optischer Einzelmolekül‐Markierungstechniken, einschließlich enzymatischer Verstärkung, molekularer Markierungen und innovativer Nanomaterialien.
Design von komplexen Mischkristall‐Elektrokatalysatoren auf Basis der Korrelation von Konfiguration, Verteilungsmustern der Adsorptionsenergie und Aktivitätskurven
Authors: Löffler Tobias , Savan Alan , Meyer Hajo , Meischein Michael , Strotkötter Valerie , Ludwig Alfred , Schuhmann Wolfgang
Published: December 2019

Komplexe Mischkristallelektrokatalysatoren (häufig auch als Hochentropielegierungen bezeichnet) gewinnen aufgrund ihrer vielversprechenden Eigenschaften zunehmend an Interesse. Mit der Fähigkeit, komplexe einphasige Mischkristalle aus fünf oder mehr Komponenten zu bilden, bieten sie einzigartige Möglichkeiten zur Feinabstimmung der Adsorptionsenergie. Allerdings ist die elementare Komplexität innerhalb der Kristallstruktur und ihr Einfluss auf die elektrokatalytischen Eigenschaften bisher kaum verstanden. Wir diskutieren, wie das Hinzufügen oder der Austausch von Elementen das Verteilungsmuster der Adsorptionsenergie beeinflusst und wie dies die Form und Aktivität der katalytischen Reaktionskurven beeinflusst. Die Auswirkungen dieser konzeptionellen Erkenntnisse auf ein verbessertes Screening neuer Katalysatorkonfigurationen wird anhand der Entdeckung und experimentellen Bewertung mehrerer hochaktiver komplexer Mischkristallelektrokatalysatoren für die Sauerstoffreduktion in alkalischen Medien diskutiert.
Fragment Coupling Reactions in Total Synthesis That Form Carbon–Carbon Bonds via Carbanionic or Free Radical Intermediates
Authors: Tomanik Martin , Hsu Ian Tingyung , Herzon Seth B.
Published: December 2019

Fragment coupling reactions that form carbon–carbon bonds are valuable transformations in synthetic design. Advances in metal‐catalyzed cross‐coupling reactions in the early 2000s brought a high level of predictability and reliability to carbon–carbon bond constructions involving the union of unsaturated fragments. By comparison, recent years have witnessed an increase in fragment couplings proceeding via carbanionic and open‐shell (free radical) intermediates. The latter has been driven by advances in methods to generate and utilize carbon‐centered radicals under mild conditions. In this Review, we survey a selection of recent syntheses that have implemented carbanion‐ or radical‐based fragment couplings to form carbon–carbon bonds. We aim to highlight the strategic value of these disconnections in their respective settings and to identify extensible lessons from each example that might be instructive to students.
Design of Complex Solid‐Solution Electrocatalysts by Correlating Configuration, Adsorption Energy Distribution Patterns, and Activity Curves
Authors: Löffler Tobias , Savan Alan , Meyer Hajo , Meischein Michael , Strotkötter Valerie , Ludwig Alfred , Schuhmann Wolfgang
Published: December 2019

Complex solid‐solution electrocatalysts (also referred to as high‐entropy alloy) are gaining increasing interest owing to their promising properties which were only recently discovered. With the capability of forming complex single‐phase solid solutions from five or more constituents, they offer unique capabilities of fine‐tuning adsorption energies. However, the elemental complexity within the crystal structure and its effect on electrocatalytic properties is poorly understood. We discuss how addition or replacement of elements affect the adsorption energy distribution pattern and how this impacts the shape and activity of catalytic response curves. We highlight the implications of these conceptual findings on improved screening of new catalyst configurations and illustrate this strategy based on the discovery and experimental evaluation of several highly active complex solid solution nanoparticle catalysts for the oxygen reduction reaction in alkaline media.
D‐A type (dfppy)2Ir(pic‐TPA) complex containing fluorinated pyridine‐2‐carboxylate ligand and triphenylamine: synthesis, photophysics and bioactivity
Authors: Bai Dan , Chen Kai , Shi Haitao , Peng Xiao , Zhang Xiaoxiao , Zheng Xuyang , Ren Hongtao , Qu Junle
Published: December 2019

A novel Ir (III) complex (dfppy)2Ir(pic‐TPA) containing fluorinated phenylpyridine and pyridine‐2‐carboxylate ancillary ligand was synthesized according to rational design, its photophysical properties and therapeutical activities examined. Radiosensitization SER values (1.63‐1.65) were observed even in radio‐resistant cell lines after treatment with this complex. Furthermore, the complexes have shown antiviral activity against HSV‐2 DNA virus. Comply with sub‐cellular distribution imaging results and molecular docking calculations and cell cytometry analysis, this Ir (III) complex demonstrated functions as promising microviscosiy and micropolarity imaging probe, also as a prodrug for combinatorial therapy of radiochemo and antiviral treatment.
Effects of terpinen‐4‐ol fumigation on protein levels of detoxification enzymes in Tribolium confusum
Authors: Liao Min , Shi Su , Wu Hailong , Yang Qianqian , Zhu Zeng , Xiao Jinjing , Huang Yong , Cao Haiqun
Published: December 2019

Terpinen‐4‐ol has high fumigating activity to stored‐grain pests including Tribolium confusum. To understand the detoxification of terpinen‐4‐ol in insects, proteomic analysis was performed to identify related proteins and pathways in response to terpinen‐4‐ol fumigation in T. confusum. By using isobaric tags for relative and absolute quantitation (iTRAQ)‐based strategy, 4,618 proteins were obtained from T. confusum adults in the present study. Comparative proteomic analysis showed that 148 proteins were upregulated and 137 proteins were downregulated in beetles under the LC50 of terpinen‐4‐ol treatment for 24 hr. According to functional classifications, differentially expressed proteins (DEPs) were enriched in xenobiotic metabolism pathways. In the detoxification pathway, the levels of 25 cytochrome P450s, 5 glutathione S‐transferases, and 2 uridine diphosphate (UDP)‐glucuronosyltransferases were changed, most of which were upregulated in T. confusum exposed to terpinen‐4‐ol. The results indicated that terpinen‐4‐ol was potentially metabolized and detoxified by enzymes like P450s in T. confusum.
Identification of novel selective Mtb‐DHFR inhibitors as antitubercular agents through structure‐based computational techniques
Authors: Sharma Kalicharan , Neshat Nazia , Sharma Shweta , Giri Namita , Srivastava Apeksha , Almalki Faisal , Saifullah Khalid , Alam Md. Mumtaz , Shaquiquzzaman Mohammad , Akhter Mymoona
Published: December 2019

Inhibition of dihydrofolate reductase from Mycobacterium tuberculosis‐dihydrofolate reductase (Mtb‐DHFR) has emerged as a promising approach for the treatment of tuberculosis. To identify novel Mtb‐DHFR inhibitors, structure‐based virtual screening (SBVS) of the Molecular Diversity Preservation International (MolMall) database was performed using Glide against the Mtb‐DHFR and h‐DHFR enzymes. On the basis of SBVS, receptor fit, drug‐like filters, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis, 16 hits were selected and tested for their antitubercular activity against the H37RV strain of M. tuberculosis. Five compounds showed promising activity with compounds 11436 and 15275 as the most potent hits with IC50 values of 0.65 and 12.51 μM, respectively, against the H37RV strain of M. tuberculosis. The two compounds were further tested in the Mtb‐DHFR and h‐DHFR enzymatic assay for selectivity and were found to be three‐ to eight‐fold selective towards Mtb‐DHFR over h‐DHFR with minimum inhibitory concentration values of 5.50, 73.89 µM and 42.00, 263.00 µM, respectively. In silico simulation studies also supported the stability of the protein–ligand complex formation. The present study demonstrates the successful utilization of in silico SBVS tools for the identification of novel and potential Mtb‐DHFR inhibitors and compound 11436 ((2,4‐dihydroxyphenyl)(3,4,5‐trihydroxyphenyl)methanone) as a potential lead for the development of novel Mtb‐DHFR inhibitors.
Gain‐of‐Function Effects of N‐Terminal CEBPA Mutations in Acute Myeloid Leukemia
Authors: Schmidt Luisa , Heyes Elizabeth , Grebien Florian
Published: December 2019

Mutations in the CEBPA gene are present in 10–15% of acute myeloid leukemia (AML) patients. The most frequent type of mutations leads to the expression of an N‐terminally truncated variant of the transcription factor CCAAT/enhancer‐binding protein alpha (C/EBPα), termed p30. While initial reports proposed that p30 represents a dominant‐negative version of the wild‐type C/EBPα protein, other studies show that p30 retains the capacity to actively regulate gene expression. Recent global transcriptomic and epigenomic analyses have advanced the understanding of the distinct roles of the p30 isoform in leukemogenesis. This review outlines direct and indirect effects of the C/EBPα p30 variant on oncogenic transformation of hematopoietic progenitor cells and discusses how studies of N‐terminal CEBPA mutations in AML can be extrapolated to identify novel gain‐of‐function features in oncoproteins that arise from recurrent truncating mutations in transcription factors.
Quantification of morphochemical changes during in situ enzymatic hydrolysis of individual biomass particles based on autofluorescence imaging
Authors: Kapsokalyvas Dimitrios , Loos Joachim , Boogers Ilco A. L. A. , Appeldoorn Maaike M. , Kabel Mirjam A. , Van Zandvoort Marc
Published: December 2019

Enzymatic hydrolysis of biomass is an established method for producing biofuels. Lignocellulosic biomass such as corn stover is very inhomogeneous material with big variation on conversion rates between individual particles therefore leading to variable recalcitrance results. In this study, we used noninvasive optical microscopy techniques, such as two‐photon microscopy and fluorescence lifetime imaging microscopy, to visualize and analyze morphological and chemical changes of individual corn stover particles pretreated with sulfuric acid during hydrolysis. Morphochemical changes were interpreted based on the fluorescence properties of isolated building blocks of plant cell wall, such as cellulose, hemicellulose, and lignin. Enzymatic hydrolysis resulted in particle size reduction, side wall collapse, decrease of second harmonic signal from cellulose, redshifting of autofluorescence emission, and lifetime decrease attributed to the relative increase of lignin. Based on these observations, tracking compositional change after hydrolysis of individual particles was accomplished. The methodologies developed offer a paradigm for imaging and analyzing enzymatic hydrolysis in vitro and in situ, which could be used for screening enzymes cocktails targeting specific recalcitrant structures or investigating locally enzyme anti‐inhibitory agents.
Noninvasive tool for optical online monitoring of individual biomass concentrations in a defined coculture
Authors: Geinitz Bertram , Rehmann Lars , Büchs Jochen , Regestein Lars
Published: December 2019

Cocultures bear great potential in the conversion of complex substrates and process intensification, as well as, in the formation of unique components only available due to inter‐species interactions. Dynamic data of coculture composition is necessary for understanding and optimizing coculture systems. However, most standard online determined parameters measure the sum of all species in the reactor system. The kinetic behavior of the individual species remains unknown. Up to now, different offline methods are available to determine the culture composition, as well as the online measurement of fluorescence of genetically modified organisms. To avoid any genetic modification, a noninvasive online monitoring tool based on the scattered light spectrum was developed for microtiter plate cultivations. To demonstrate the potential, a coculture consisting of the bacterium Lactococcus lactis and the yeast Kluyveromyces marxianus was cultivated. Via partial least squares regression of scattered light spectra, the online determination of the individual biomass concentrations without further sampling and analyses is possible. The results were successfully validated by a Coulter counter‐analysis, taking advantage of the different cell sizes of both organisms. The findings prove the applicability of the new method to follow in detail the dynamics of a coculture.
A simple microsphere‐based mold to rapidly fabricate microwell arrays for multisize 3D tumor culture
Authors: Li Zixiu , Guo Xiaofang , Sun Lili , Xu Juan , Liu Wenming , Li Tianbao , Wang Jinyi
Published: December 2019

Three‐dimensional (3D) tumor has been considered as the best in vitro model for cancer research. In recent years, various methods have been developed to controllable prepare multisize 3D tumors. Nonetheless, reported technologies are still problematic and difficult to produce 3D tumors with highly uniform size and cell content. Here, a novel and simple microsphere‐based mold approach is proposed to rapidly fabricate spherical microwell arrays for multisize 3D tumors formation, culture, and recovery. Larger amounts of HepG2 3D tumors with excellent quality and uniformity can be efficiently generated using this method. In addition, the tumor size can also be simply controlled by adjusting the diameter of the microwell arrays. All experimental results indicated that the proposed method offers a promising platform to generate and recover highly controlled multisize 3D tumors for various cell‐based biomedical research.
Impact of postoperative complications on disease recurrence and long-term survival following oesophagogastric cancer resection
Authors: Saunders J H , Yanni F , Dorrington M S , Bowman C R , Vohra R S , Parsons S L
Published: December 2019

Background

Postoperative complications after resection of oesophagogastric carcinoma can result in considerable early morbidity and mortality. However, the long-term effects on survival are less clear.

Methods

All patients undergoing intentionally curative resection for oesophageal or gastric cancer between 2006 and 2016 were selected from an institutional database. Patients were categorized by complication severity according to the Clavien–Dindo classification (grades 0–V). Complications were defined according to an international consensus statement. The effect of leak and severe non-leak-related complications on overall survival, recurrence and disease-free survival was assessed using Kaplan–Meier analyses to evaluate differences between groups. All factors significantly associated with survival in univariable analysis were entered into a Cox multivariable regression model with stepwise elimination.

Results

Some 1100 patients were included, with a median age of 69 (range 28–92) years; 48·1 per cent had stage III disease and cancer recurred in 428 patients (38·9 per cent). Complications of grade III or higher occurred in 244 patients (22·2 per cent). The most common complications were pulmonary (29·9 per cent), with a 13·0 per cent incidence of pneumonia. Rates of atrial dysrhythmia and anastomotic leak were 10·0 and 9·6 per cent respectively. Patients with a grade III–IV leak did not have significantly reduced overall survival compared with those who had grade 0–I complications. However, patients with grade III–IV non-leak-related complications had reduced median overall survival (19·7 versus 42·7 months; P < 0·001) and disease-free survival (18·4 versus 36·4 months; P < 0·001). Cox regression analysis identified age, tumour stage, resection margin and grade III–IV non-leak-related complications as independent predictors of poor overall and disease-free survival.

Conclusion

Beyond the acute postoperative period, anastomotic leak does not adversely affect survival, however, other severe postoperative complications do reduce long-term overall and disease-free survival.
Multicentre study of prepectoral breast reconstruction using acellular dermal matrix
Authors: Chandarana M. , Harries S.
Published: December 2019

Background

Single-stage reconstruction is used widely after mastectomy. Prepectoral implant placement is a relatively new technique. This multicentre audit examined surgical outcomes following prepectoral reconstruction using acellular dermal matrix (ADM).

Methods

All patients who had a mastectomy with prepectoral breast reconstruction and ADM in the participating centres between January 2015 and December 2017 were included. Demographic and treatment details, and short- and long-term operative outcomes were recorded. Factors affecting complications and implant loss were analysed: age, BMI, smoking status, diabetes, vascular disease, laterality of surgery, previous ipsilateral breast surgery or radiotherapy, indication for surgery (invasive versus in situ carcinoma, or risk reduction), type of mastectomy, axillary clearance, breast volume, implant volume, and neoadjuvant and adjuvant chemotherapy.

Results

A total of 406 reconstructions were performed across 18 centres. Median follow-up was 9·65 months. Median hospital stay was 1 day. The 90-day unplanned readmission rate was 15·7 per cent, and the return-to-theatre rate 16·7 per cent. Some 15·3 per cent of patients had a major complication, with a 90-day implant loss rate of 4·9 per cent. A further six patients had delayed implant loss. In multivariable analysis, no factor was significantly associated with complications or implant loss.

Conclusion

Prepectoral breast reconstruction with ADM has satisfactory surgical outcomes. The duration of follow-up needs to be extended to examine outcomes in patients who received adjuvant radiotherapy.
Forming automatic groups of learners using particle swarm optimization for applications of differentiated instruction
Authors: Zervoudakis Konstantinos , Mastrothanasis Konstantinos , Tsafarakis Stelios
Published: December 2019

The aim of this paper is to present a method that uses computational intelligence techniques to classify students according to the principles of differentiated instruction. A clustering algorithm based on particle swarm optimization is applied to two sets of data emerging from the holistic assessment of the student's particular characteristics and needs. The results illustrate the algorithm's contribution to the effective formation of heterogeneous student groups, with the members of each having homogeneous characteristics of skills, difficulties, psychosocial and cognitive profiles. Thus, the teacher can easily manage students, by knowing the characteristics of each group. A comparison with a genetic algorithm as well as cuckoo search algorithm shows that the proposed method provides improved categorization capabilities.
Using Mathcad to facilitate the design of chemical reactors involving multiple reactions
Authors: Cuadri Antonio A. , Martín‐Alfonso José E. , Urbano Juan
Published: December 2019

The pedagogy of teaching chemical reaction engineering is continually advancing through the use of new computational tools and, therefore, the integration of these new tools into the Chemical Engineering degree is challenging. This paper reports an educational experience dealing with the use of Mathcad software to complement and to facilitate the design of chemical reactors involving multiple reactions. A continuous stirred‐tank reactor taking place series reactions and two reactors (continuous stirred‐tank reactor or plug flow reactor) arranged in series involving parallel reactions were presented as case studies. This experience, which was carried out with the third‐year chemical engineering students enrolled in the chemical reactors course, revealed that Mathcad facilitates the understanding of the theoretical concepts related to multiple reactions and also reduces the complexity of mathematical calculation to a minimum. Thus, the use of this computer tool allows the teacher (a) to delve deeper into more issues related to the design of chemical reactors, and (b) to consider this tool perfectly useful for other courses corresponding to the Chemical Engineering degree.
Strategies for the Targeted Improvement of Anodic Electron Transfer in Microbial Fuel Cells
Authors: Heydorn Raymond Leopold , Engel Christina , Krull Rainer , Dohnt Katrin
Published: December 2019

The concept of the microbial fuel cell (MFC) has existed for over 100 years, but only within the last decade, the practical implementation has become conceivable due to microbial and technical progress. This review article presents available strategies to increase the limiting extracellular electron transfer (EET) in the anode space of MFCs. Therefore, organism‐based improvements as well as the effects of (bio–)polymers and redox mediators on ETT will be demonstrated.
A Structural Rationale for N‐Methylbicuculline Acting as a Promiscuous Competitive Antagonist of Inhibitory Pentameric Ligand‐Gated Ion Channels
Authors: Jones Mathew J. , Dawson Alice , Hales Tim G. , Hunter William N.
Published: December 2019

Bicuculline, a valued chemical tool in neurosciences research, is a competitive antagonist of specific GABAA receptors and affects other pentameric ligand‐gated ion channels including the glycine, nicotinic acetylcholine and 5‐hydroxytryptamine type 3 receptors. We used a fluorescence‐quenching assay and isothermal titration calorimetry to record low‐micromolar dissociation constants for N‐methylbicuculline interacting with acetylcholine‐binding protein and an engineered version called glycine‐binding protein (GBP), which provides a surrogate for the heteromeric interface of the extracellular domain of the glycine receptor (GlyR). The 2.4 Å resolution crystal structure of the GBP:N‐methylbicuculline complex, sequence and structural alignments reveal similarities and differences between GlyR and the GABAA receptor–bicuculline interactions. N‐methylbicuculline displays a similar conformation in different structures, but adopts distinct orientations enforced by interactions and steric blocks with key residues and plasticity in the binding sites. These features explain the promiscuous activity of bicuculline against the principal inhibitory pentameric ligand‐gated ion channels in the CNS.
Clear cell sarcoma of the esophagus: A rare location
Authors: Yahyaoui Yosra , Zenzri Yosr , Behi Khalil , Boujelbene Nadia , Mokrani Amina , Abbas Imen , Mrad Karima , Mezlini Amel
Published: December 2019

Clear cell sarcoma of the esophagus is very rare. The etiology of this neoplasm remains unknown. Confirmed diagnosis requires histopathology with immunochemistry and molecular study. CCS typically shows highly aggressive behavior with a high rate of local recurrence, metastases, and death from disease.
Magnetic Hybrid Wax Nanocomposites as Externally Controlled Theranostic Vehicles: High MRI Enhancement and Synergistic Magnetically Assisted Thermo/Chemo Therapy
Authors: de Moura Carolina L. , Gallo Juan , García‐Hevia Lorena , Pessoa Otília D. L. , Ricardo Nágila M. P. S. , Bañobre‐López Manuel
Published: December 2019

To fight against cancer, smarter drugs and drug delivery systems are required both to boost the efficiency of current treatments while reducing deleterious side effects, and combine diagnosis/monitoring with therapy (theranosis) in the search for the final goal of personalized medicine. This work presents the design, preparation, and proof‐of‐principle validation of a novel hybrid organic–inorganic nanocomposite joining together non‐invasive imaging capabilities through magnetic resonance imaging and externally actuated therapeutic properties through a combination of chemo‐ and thermotherapy. The lipidic matrix of the nanocomposite was composed of carnauba wax, which was simultaneously dual loaded with magnetite nanoparticles and the anticancer drug Oncocalyxone A. Obtained formulations were fully characterized and showed outstanding performances as T2‐contrast agents in magnetic resonance imaging (r2>800 mm−1 s−1), heat generating sources in magnetic hyperthermia (specific absorption rate, SAR>200 W g−1Fe), and magnetically responsive drug delivery vehicles. The potential of the designed formulations as theranostic agents was validated in vitro and results indicated a synergistic thermo/chemotherapeutic effect derived from heat generation and controlled drug delivery to cancer growth. Thereby, this external control over the drug delivery profile and the integrated imaging capability open the door to personalized cancer medicine and real‐time monitoring of tumor progression.
Expansion of Magnetic Aromaticity Criteria to Multilayer Structures: Magnetic Response and Spherical Aromaticity of Matryoshka‐Like Cluster [Sn@Cu12@Sn20]12−
Authors: Kulichenko Maksim , Fedik Nikita , Boldyrev Alexander , Muñoz‐Castro Alvaro
Published: December 2019

Structural characterization of the discrete [Sn@Cu12@Sn20]12− cluster exposed a fascinating architecture composed of three concentric structural layers in which an endohedral Sn atom is enclosed in a Cu12 icosahedron, which in turn is embedded in an Sn20 dodecahedron. Herein, the possibility of sustaining aromatic behavior for this prototypical multilayered species was evaluated, in order to extend this concept to more complex clusters on the basis of magnetic response and bonding analysis by the AdNDP approach. This revealed characteristic features of spherical aromatics, given by the ability to sustain the shielding cone property, similar to archetypal aromatics. The favorable bonding pattern in the [Sn@Cu12@Sn20]12− cluster fulfills the 2(N+1)2 Hirsch rule for aromaticity; thus, the cluster could be regarded as a first member of aromatic multilayered structures. The set of four 13c–2e aromatic bonds that was identified in the internal SnCu12 structure results in spherical aromatic character of this multilayered cluster. This insight builds a bridge between the traditional concept of Hückel's aromaticity and the aromaticity of complex and stable 3D systems that may be explored on the basis of magnetic response and bonding analysis. It also may open a way to novel findings in bottled clusters displaying aromatic behavior in multilayer structures, which are of great interest for inorganic nano‐ and material sciences due to their unprecedented stability.
Considering adjuvant therapy for stage II melanoma
Authors: Poklepovic Andrew S. , Luke Jason J.
Published: December 2019

Melanoma is among the few cancers that demonstrate an increasing incidence over time. Simultaneously, this trend has been marked by an epidemiologic shift to earlier stage at diagnosis. Before 2011, treatment options were limited for patients with metastatic disease, and the median overall survival was less than 1 year. Since then, the field of melanoma therapeutics has undergone major changes. The use of anti–CTLA‐4 and anti‐PD1 immune checkpoint inhibitors and combination BRAF/MEK inhibitors for patients with BRAF V600 mutations has significantly extended survival and allowed some patients to remain in durable disease remission off therapy. It has now been confirmed that these classes of agents have a benefit for patients with stage III melanoma after surgical resection, and anti‐PD1 and BRAF/MEK inhibitors are standards of care in this setting. Some patients with stage II disease (lymph node‐negative; American Joint Committee on Cancer stage IIB and IIC) have worse melanoma‐specific survival relative to some patients with stage III disease. Given these results, expanding the population of patients who are considered for adjuvant therapy to include those with stage II melanoma has become a priority, and randomized phase 3 clinical trials are underway. Moving into the future, the validation of patient risk‐stratification and treatment‐benefit prediction models will be important to improve the number needed to treat and limit exposure to toxicity in the large population of patients with early stage melanoma.