bluuebunny/crossref_metadata_2025 huggingface dataset:
Om jalousitemaet hos Proust
Authors: Buvik Per
Published: October 2016

Per Buvik: “On the Theme of Jealousy in Proust”In Proust, there is generally no love without jealousy. More surprisingly, jealousy is even prior to love, which is, then, derived from jealousy. Love is consequently dominated by uncertainty, suspiciousness, and anguish, represented as rooted in early childhood. Suffering from a never surmounted Oedipus complex, Proust’s narrator and main character constantly compares his girlfriend Albertine with his mother when he was a child, longing for the same intimacy, but also fearing the same “treachery” that he experienced with her. Only long-lasting separation or boredom due to long-lasting daily life together can eliminate jealousy. The problem is that love also disappears when there is no jealousy.
Søvnens tid og rum. Om at læse søvnen i På sporet af den tabte tid
Authors: Ulrich Jacob
Published: October 2016

Jacob Ulrich: “The Time and Space of Sleep: Reading Sleep in In Search of Lost Time”This article examines the significance and structuring function of sleep and sleep related instances in Marcel Proust’s In Search of Lost Time. Through close readings of narrative conceptions of time in the ouverture the article shows how descriptions of the narrator’s sleep both destabilize the narrative and form a narrative pattern to which the overall structure of the novel adheres. Secondly, the article focuses on spatiality and sleep, particularly the narrator’s bedroom, which appears as a privileged place where certain perceptual conditions are displayed and experimented with. Descriptions of sleep in the novel thus form a boundary or threshold that negotiates between inner and outer modes of perception. The article concludes by addressing, in more general terms, the potential problems involved when studying ‘sleep and literature’.
Redaktionelt forord
Authors: Passage Passage
Published: October 2016

Genrer styrer alle dele af det litterære kredsløb: Forfatterens skrift, forlagenes markedsføring, bibliotekernes katalogisering, læserens forventninger og kritikernes domme.Vi orienterer os hele tiden efter genrer. Litteraturhistorien sætter skel ud fra genreinddelinger, og vi anser ofte de værker, der bryder med genrekonventioner og hæver sig over formelagtig 'genrelitteratur' for at være af høj litterær kvalitet. Vores litterære forventningshorisont præges af genremærkater, og vi regner med en vis grad af generisk stabilitet. Samtidig kommer der stadig nye genrer til som 'autofiktion' og 'selvnarration', der sætter spørgsmålstegn ved grænsedragninger mellem traditionelle genrer som 'roman' og 'biografi'.Passage nr. 74 sætter fokus på genrer. Nummeret udfordrer, hvad der ofte tages for givet om emnet, og udforsker nye aspekter ved de litterære konventioner. Blandt de emner, artiklerne behandler, er spørgsmålet om, hvad litteraturvidenskaben stiller op med alle de værker, der falder uden for de 'finlitterære' genrer, litteraturhistorien traditionelt behandler. Andre spørgsmål lyder, hvad det vil sige, at en roman er en fiktionsgenre, og hvordan en veletableret genre som lyrik kan vedblive at udfordre. Endelig viser nummeret, hvordan genrer kan gå på tværs af kunstarter, det undersøger, hvordan genrer kan være knyttet til affekt, og hvorfor man i de seneste år har set en stigende brug af utraditionelle genremærkater. Dette nummer af Passage behandler således aktuelle dimensioner af et klassisk begreb. Derudover rummer nummeret en artikel uden for genretemaet om nostalgi hos den tyske forfatter W.G. Sebald.
Genrer og hårde data
Authors: Handesten Lars
Published: October 2016

Lars Handesten: “Genre Concepts and Hard Data”The article discusses Franco Moretti’s concepts of genre, his use of data, and his notion ‘distant reading’. Moretti’s ideas are welcomed but adjusted in accordance with the genre concept suggested by Alistair Fowler. The article aims at establishing a moderated and pragmatic method for the use of quantitative research. Additionally, the concept of ‘genre literature’ is critically examined in order to make it an object of literary studies.
Genresignaturen. En retorisk nydannelse
Authors: Nyboe Jacob Ølgaard
Published: October 2016

Jacob Ølgaard Nyboe: “Genre Signature. A Rhetorical Neologism ”The article introduces the notion of genre signature defined as a creative, unique or deliberately misguiding genre label. It is argued that the genre signature holds a great rhetorical potential in negotiating the position as well as the interpretation of a literary work. The phenomenon is examined through analyses of contemporary Danish literature and is viewed in the context of Rhetorical Genre Studies (RGS), new literary tendencies and media reception.
Elegiske sensibiliteter. Følelsens æstetik set fra en genre.
Authors: Lønneker Ane Martine Kjær
Published: October 2016

Ane Martine Kjær Lønneker: “Elegiac Sensibilities. The Aesthetics of Feeling from the Point of View of Genre”The article discusses the concept of mode and examines the historical circumscription of the elegiac mode. This is done with special regard to the 18th century critical writings on distinctive feelings connected to the elegy. The article argues that the components that make up a mode in the case of the elegiac are associated with an affective repertoire. The 18th century idea of mode as Empfindungsweise (Schiller) can thus be regarded as an incitement to study how genres frame emotional tonalities and how aesthetic feelings are cultivated by historical genre discourses.
Lyrik? En refleksion over den lyriske genres aktuelle status
Authors: Mønster Louise
Published: October 2016

Louise Mønster: “Poetry? A Reflection on the Status of the Poetic Genre”The article raises the question of genre in relation to contemporary poetry. The point of departure is the mismatch between the ordinary understanding of poetry as a short literary form that expresses the experiences, thoughts and feelings of a subject, and the actual ways in which much contemporary poetry unfolds. The article discusses why it is still relevant to sustain the concept of poetry, and it points out four factors that are believed to play an important role in explaining why the established concept of poetry has come under pressure in recent years. These factors have to do with mediatization, literary culture, forms of publication and increased politicization.
Kjerlighedens Gjerninger
Authors: Rønnov-Jessen Peter
Published: October 2016

Peter Rønnov-Jessen: Kjerlighedens Gjerninger
Honoré de Balzac: Galskab, ideologi og diskursens økonomi
Authors: Felman Shoshana
Published: October 2016

Shoshana Felman: Honoré de Balzac: Galskab, ideologi og diskursens økonomi
Gruppeudstilling (digt)
Authors: Hultberg Peer
Published: October 2016

Peer Hultberg: Gruppeudstilling (digt)
Digt
Authors: Juul Pia
Published: October 2016

Digt af Pia Juul
Midt på dagen (digt)
Authors: Nielsen Lean
Published: October 2016

Lean Nielsen: Midt på dagen (digt)
Digt
Authors: Laugesen Peter
Published: October 2016

Digt af Peter Laugesen
Depression and Age at First Neurology Appointment Associated with Receipt of Behavioral Medicine Services Within 1 Year in a Multiple Sclerosis Population
Authors: Greenberg Benjamin , Fan Youran , Carriere Lucille , Sullivan Amy
Published: October 2016

Background:

Patients with multiple sclerosis (MS) newly seen by a neurologist may benefit from early psychological intervention owing to the reciprocal relationship between stress and disease progression. However, it is uncertain what factors contribute to patients' receiving these services.

Methods:

Logistic regression analysis of prospectively gathered data evaluated how demographic and disease characteristics and emotional/physical health factors contributed to referral to receive behavioral medicine (BM) services within 1 year of their first neurology appointment at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic. Survival analyses then evaluated whether this resulted in earlier receipt of services.

Results:

Although many factors were associated with receiving BM services during univariate analyses (age, race, marital status, years since MS onset, depression, stress, and quality of life), when considering multivariable interactions, only two variables remained significant: age (odds ratio [OR] = 0.86, 95% confidence interval [CI], 0.80–0.92) and depression (OR = 1.56, 95% CI, 1.39–1.75). Survival analyses did not show differences in time to BM services for stratifications of age or depression scores.

Conclusions:

Younger patients and patients with more severe depression were more likely to receive BM services within 1 year of their first neurology appointment. Future research will focus on evaluating whether these are also the patients in greatest need of services or whether they are simply more open to receiving them.
Eruptive activity at Turrialba volcano (Costa Rica): Inferences from 3He/4He in fumarole gases and chemistry of the products ejected during 2014 and 2015
Authors: Rizzo Andrea Luca , Di Piazza Andrea , de Moor J. Maarten , Alvarado Guillermo E. , Avard Geoffroy , Carapezza Maria Luisa , Mora Mauricio M.
Published: October 2016

A new period of eruptive activity started at Turrialba volcano, Costa Rica, in 2010 after almost 150 years of quiescence. This activity has been characterized by sporadic explosions whose frequency clearly increased since October 2014. This study aimed to identify the mechanisms that triggered the resumption of this eruptive activity and characterize the evolution of the phenomena over the past 2 years. We integrate 3He/4He data available on fumarole gases collected in the summit area of Turrialba between 1999 and 2011 with new measurements made on samples collected between September 2014 and February 2016. The results of a petrological investigation of the products that erupted between October 2014 and May 2015 are also presented. We infer that the resumption of eruptive activity in 2010 was triggered by a replenishment of the plumbing system of Turrialba by a new batch of magma. This is supported by the increase in 3He/4He values observed since 2005 at the crater fumaroles and by comparable high values in September 2014, just before the onset of the new eruptive phase. The presence of a number of fresh and juvenile glassy shards in the erupted products increased between October 2014 and May 2015, suggesting the involvement of new magma with a composition similar to that erupted in 1864–1866. We conclude that the increase in 3He/4He at the summit fumaroles since October 2015 represents strong evidence of a new phase of magma replenishment, which implies that the level of activity remains high at the volcano.
Quantitative estimation of the contribution of dust sources to Chinese loess using detrital zircon U‐Pb age patterns
Authors: Zhang Hanzhi , Lu Huayu , Xu Xisheng , Liu Xiaoming , Yang Tao , Stevens Thomas , Bird Anna , Xu Zhiwei , Zhang Tian , Lei Fang , Feng Han
Published: October 2016

The origin and provenance of the loess deposits of the Chinese Loess Plateau (CLP) are still debated. In order to pinpoint the dust sources, surface samples from the piedmont of the Northeastern Tibetan Plateau, the Gobi Altai Mountains, and modern eolian dunes from the Tengger desert and Mu Us sand field were analyzed by using the detrital zircon dating technique. In order to quantitatively discriminate the content of different potential sources, zircon grains of different ages were grouped according to their tectonic origin. Zircon grains aged from 1300 to 550 Ma were assigned to the Northeastern Tibetan Plateau, and grains aged from 550 to 0 Ma to the Northeastern Tibetan Plateau or the Gobi Altai Mountains, or to a combination of the two. Zircon ages of around 2.8 Ga to 1.3 Ga may be a mixture of sources from the Northeastern Tibetan Plateau, Gobi Altai Mountains, or North China Craton. Sediments from the Tengger desert and Mu Us sand field consist of a mixture of the three sources and exhibit a high degree of spatial variability in terms of their source. In the northern part of the two deserts, 43–83% of the sediments are derived from the Gobi Altai Mountains, while in the south, material from the Northeastern Tibetan Plateau comprises 51–98% of the sediments. Loess deposits from the CLP also comprise a mixture of the three different sources, with material from the Northeastern Tibetan Plateau making the dominant contribution (65–100%), with material from the North China Craton and the Gobi Altai Mountains comprising 0–35% and 0–40% of the loess deposits, respectively. The contributions from the three sources to the loess deposits on CLP vary spatially. Application of the novel statistical method of provenance group analysis demonstrates that the loess deposits comprise a mixture of material from a broad region of northern China and that the Northeastern Tibetan Plateau material makes the dominant contribution.
Organoaluminum Compounds and
L
ewis Pairs
Authors: Layh Marcus , Uhl Werner , Bouhadir Ghenwa , Bourissou Didier
Published: October 2016

This chapter is dedicated to bifunctional derivatives associating Al with P‐ or N‐containing Lewis bases. The synthesis and structure of these Lewis pairs/ambiphilic derivatives are described (presence or not of P/N → Al interactions). Both unimolecular and bimolecular compounds are considered. Their reactivity towards small molecules (CO
2
, alkene, alkynes, isocyanides, amine‐boranes, BX
3
, hydrides, and so on) including catalytic transformations are then presented. The synthesis and reactivity of transition metal complexes deriving from Al/P ambiphilic ligands are also presented. Whenever possible, the Al‐compounds are compared to their lighter B congeners.
The role of intrinsic and extrinsic rewards in committing violence during combat: A cross‐sectional study with former combatants in the DR Congo
Authors: Haer Roos , Hermenau Katharin , Elbert Thomas , Moran James K. , Hecker Tobias
Published: October 2016

It has been postulated that the violent behavior that characterizes armed conflict is reinforced by the possibility of receiving rewards. The present study examined the potential influence of two types of rewards in an ongoing setting of conflict: extrinsic and intrinsic rewards. Former combatants active in the Democratic Republic of the Congo (N = 198) were interviewed and questioned about the way they were recruited, the offenses they committed during combat, their level of perceived intrinsic rewards (i.e., appetitive perception of violence), and the number of received extrinsic rewards during their time in the armed group (e.g., money, extra food, alcohol, or drugs). A moderated multiple regression analysis showed that the number of received extrinsic rewards and the level of intrinsic rewards were significantly positively related to the number of different types of offenses committed. In contrast to our expectations and previous findings, the recruitment type (forced conscription vs. voluntary enlistment) did not moderate this relation. Our findings suggest that both types of rewards play a role in committing violence during combat. We suggest, therefore, that reintegration programs should not only consider the influence of extrinsic rewards, but also need to address the influence of intrinsic rewards to counter violent behavior among former combatants. Aggr. Behav. 43:241–250, 2017. © 2016 Wiley Periodicals, Inc.
Cross‐Cultural and Construct Validity of the Animated Activity Questionnaire
Authors: Peter Wilfred F. , de Vet Henrika C. W. , Boers Maarten , Harlaar Jaap , Roorda Leo D. , Poolman Rudolf W. , Scholtes Vanessa A. B. , Steultjens Martijn , Hendry Gordon J. , Roos Ewa M. , Guillemin Francis , Benedetti Maria G. , Cavazzuti Lorenzo , Escobar Antonio , Dagfinrud Hanne , Terwee Caroline B.
Published: October 2016

Objective

The Animated Activity Questionnaire (AAQ) assesses activity limitations in patients with hip/knee osteoarthritis and consists of video animations; the patients choose the animation that best matches their own performance. The AAQ has shown good validity and reliability. This study aims to evaluate cross‐cultural and construct validity of the AAQ.

Methods

Cross‐cultural validity was assessed using ordinal logistic regression analysis to evaluate differential item functioning (DIF) across 7 languages. Construct validity was assessed by testing correlations between the AAQ and a patient‐reported outcome measure (PROM) and performance‐based tests.

Results

Data from 1,239 patients were available. Compared to the Dutch language (n = 279), none of the 17 items showed DIF in English (n = 202) or French (n = 193), 1 item showed uniform DIF in Spanish (n = 99) and Norwegian (n = 62), and 2 items showed uniform DIF in Danish (n = 201). In all these languages, the occurrence of DIF did not influence the total score, which remained comparable with the original Dutch version. For Italian (n = 203) versus Dutch, however, 6 items showed uniform DIF, and 1 item showed nonuniform DIF, indicating some problems with the cross‐cultural validity between these countries. With regard to construct validity, the correlations with PROM (0.74) and performance‐based tests (0.36–0.68) were partly as expected (>0.60).

Conclusion

The AAQ, an innovative tool to measure activity limitations that can be placed on the continuum between PROMs and performance‐based tests, showed a good overall cross‐cultural validity, and seems to have great potential for international use in research and daily clinical practice in many European countries.
Self‐Management Education Participation Among US Adults With Arthritis: Who's Attending?
Authors: Murphy Louise B. , Brady Teresa J. , Boring Michael A. , Theis Kristina A. , Barbour Kamil E. , Qin Jin , Helmick Charles G.
Published: October 2016

Objective

Self‐management education (SME) programs teach people with chronic conditions skills to manage their health conditions. We examined patterns in SME program participation among US adults with arthritis ages ≥18 years.

Methods

Respondents with arthritis were those who reported ever being diagnosed with arthritis by a doctor or health care provider. We analyzed 2014 National Health Interview Survey data to estimate the percentage (unadjusted and age‐standardized) who ever attended an SME program overall and for selected subgroups, representativeness of SME participants relative to all adults with arthritis, and trends in SME course participation.

Results

In 2014, 1 in 9 US adults with arthritis (11.3% [95% confidence interval (95% CI) 10.4–12.3]; age‐standardized 11.4% [95% CI 10.0–12.9]) had ever participated in an SME program. SME participation (age‐standardized) was highest among those with ≥8 health care provider visits in the past 12 months (16.0% [95% CI 13.1–19.4]). Since 2002, the number of adults with arthritis who have ever participated in SME has increased by 1.7 million, but the percentage has remained constant.

Conclusion

Despite its many benefits, SME participation among US adults with arthritis remains persistently low. By recommending that their patients attend SME programs, health care providers can increase the likelihood that their patients experience SME program benefits.
Bioinspired Multifunctional Ceramic Platelet‐Reinforced Piezoelectric Polymer Composite
Authors: Xu Zhe , Bykova Julia , Baniasadi Mahmoud , Moreno Salvador , Zhou Zhong , Das Nandita , Bandi Sasaank , Xi Yang , Qian Dong , Baughman Ray H. , Minary‐Jolandan Majid
Published: October 2016

Hybrid materials of inorganic–organic phases in which each phase provides different functionality are attractive candidates for achieving multifunctionality. Using a layer‐by‐layer approach, we fabricated sheets of piezoelectric polymer P(VDF‐TrFE) reinforced by aligned sub‐micron thick sapphire platelets. The films were transparent and piezoelectric, exhibited ductility up to ≈330%, and tensile toughness of up to 26 J g–1. We investigated the effect of thermal annealing on the crystallinity of the polymer phase and its effect on the mechanical and piezoelectric properties of the films. Thermal annealing resulted in improvement of the elastic modulus and piezoelectric properties of the films. in situ SEM tensile experiments were conducted for observation of the deformation mechanism of the films.
Simulation of NOx and soot abatement with Cu‐Cha and Fe‐ZSM5 catalysts
Authors: Bensaid Samir , Balakotaiah Vemuri , Luss Dan
Published: October 2016

The embodiment of the NOx selective catalytic reduction (SCR) functionality in a diesel particulate filter (DPF), so‐called SCR‐on‐Filter (SCRoF), is investigated through numerical modeling with SCR kinetics corresponding to Cu‐Chabazite and Fe‐ZSM5 catalysts. The results of the simulations of the SCR activity, performed in the absence and presence of soot, indicate that the presence of soot negligibly affects the NOx conversion efficiency, given the slow dynamics of passive regeneration. Conversely, the reduction in cake thickness by soot passive oxidation is significantly different in the absence of SCR activity (uncatalyzed DPF) compared to that in its presence (SCRoF). In fact, in the SCRoF only 60–80% of the original soot consumption obtained in the absence of SCR reaction over 1 h can be achieved. Individual Cu‐Chabazite and Fe‐ZSM5 catalysts, as well as in‐series layers of the two catalysts, are investigated to devise the widest temperature window for SCRoF. © 2016 American Institute of Chemical Engineers AIChE J, 63: 238–248, 2017
A Chinese patient with Toriello–Carey syndrome and an interstitial deletion of 3q
Authors: Xie Lulu , Luo Xianqiong , Yang Jie , Wang Junping , Nie Chuan , Wang Zhu
Published: October 2016

Toriello–Carey syndrome (T–CS), which was first described by Toriello and Carey, is a rare multiple congenital anomaly syndrome characterized by agenesis of the corpus callosum, Pierre Robin sequence, unusual facial appearance, and other anomalies. Tracheal or laryngeal anomalies are reported as a common manifestation of T–CS. These anomalies can lead to respiratory distress and respiratory tract infection. The cause of T–CS is unknown, although there have been reports of patients with a clinical diagnosis of T–CS and a chromosome anomaly. We describe another such patient who was found to have an interstitial deletion of 3q (3q12.1‐q21.3). © 2016 Wiley Periodicals, Inc.
Kinetic and Theoretical Studies on Ni0/N‐Heterocyclic Carbene‐Catalyzed Intramolecular Alkene Hydroacylation
Authors: Hoshimoto Yoichi , Hayashi Yukari , Ohashi Masato , Ogoshi Sensuke
Published: October 2016

A combined kinetic and theoretical study was conducted in order to clarify the details on the reaction mechanism for Ni0/ItBu‐catalyzed intramolecular alkene hydroacylation. The results confirm the hypothesis that this intramolecular hydroacylation proceeds through an oxanickelacycle key intermediate.
Optimizing carbon dioxide utilization for microalgae biofilm cultivation
Authors: Blanken Ward , Schaap Stefan , Theobald Sophie , Rinzema Arjen , Wijffels René H. , Janssen Marcel
Published: October 2016

The loss of carbon dioxide (CO2) to the environment during microalgae cultivation is undesirable for both environmental and economic reasons. In this study, a phototrophic biofilm growth model was developed and validated with the objective to maximize both CO2 utilization efficiency and production of microalgae in biofilms. The model was validated in growth experiments with CO2 as the limiting substrate. The CO2 utilization and biomass productivity were maximized by changing the gas flow rate, the number of biofilm reactors in series and gas composition. Based on simulations, the maximum CO2 utilization efficiency that was reached was 96% based on a process employing flue gas. The corresponding drop in productivity was only 2% in comparison to the non‐CO2 limited reference situation. In order to achieve this, 25 biofilm reactors units, or more, must be operated in series. Based on these results, it was concluded that concentrated CO2 streams and plug flow behavior of the gaseous phase over the biofilm surface are essential for high productivity and CO2 utilization efficiency. Biotechnol. Bioeng. 2017;114: 769–776. © 2016 Wiley Periodicals, Inc.
Oxygen mapping: Probing a novel seeding strategy for bone tissue engineering
Authors: Westphal Ines , Jedelhauser Claudia , Liebsch Gregor , Wilhelmi Arnd , Aszodi Attila , Schieker Matthias
Published: October 2016

Bone tissue engineering (BTE) utilizing biomaterial scaffolds and human mesenchymal stem cells (hMSCs) is a promising approach for the treatment of bone defects. The quality of engineered tissue is crucially affected by numerous parameters including cell density and the oxygen supply. In this study, a novel oxygen‐imaging sensor was introduced to monitor the oxygen distribution in three dimensional (3D) scaffolds in order to analyze a new cell‐seeding strategy. Immortalized hMSCs, pre‐cultured in a monolayer for 30–40% or 70–80% confluence, were used to seed demineralized bone matrix (DBM) scaffolds. Real‐time measurements of oxygen consumption in vitro were simultaneously performed by the novel planar sensor and a conventional needle‐type sensor over 24 h. Recorded oxygen maps of the novel planar sensor revealed that scaffolds, seeded with hMSCs harvested at lower densities (30–40% confluence), exhibited rapid exponential oxygen consumption profile. In contrast, harvesting cells at higher densities (70–80% confluence) resulted in a very slow, almost linear, oxygen decrease due to gradual achieving the stationary growth phase. In conclusion, it could be shown that not only the seeding density on a scaffold, but also the cell density at the time point of harvest is of major importance for BTE. The new cell seeding strategy of harvested MSCs at low density during its log phase could be a useful strategy for an early in vivo implantation of cell‐seeded scaffolds after a shorter in vitro culture period. Furthermore, the novel oxygen imaging sensor enables a continuous, two‐dimensional, quick and convenient to handle oxygen mapping for the development and optimization of tissue engineered scaffolds. Biotechnol. Bioeng. 2017;114: 894–902. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
An expression tag toolbox for microbial production of membrane bound plant cytochromes P450
Authors: Vazquez‐Albacete Dario , Cavaleiro Ana Mafalda , Christensen Ulla , Seppälä Susanna , Møller Birger Lindberg , Nørholm Morten H. H.
Published: October 2016

Membrane‐associated Cytochromes P450 (P450s) are one of the most important enzyme families for biosynthesis of plant‐derived medicinal compounds. However, the hydrophobic nature of P450s makes their use in robust cell factories a challenge. Here, we explore a small library of N‐terminal expression tag chimeras of the model plant P450 CYP79A1 in different Escherichia coli strains. Using a high‐throughput screening platform based on C‐terminal GFP fusions, we identify several highly expressing and robustly performing chimeric designs. Analysis of long‐term cultures by flow cytometry showed homogeneous populations for some of the conditions. Three chimeric designs were chosen for a more complex combinatorial assembly of a multigene pathway consisting of two P450s and a redox partner. Cells expressing these recombinant enzymes catalyzed the conversion of the substrate to highly different ratios of the intermediate and the final product of the pathway. Finally, the effect of a robustly performing expression tag was explored with a library of 49 different P450s from medicinal plants and nearly half of these were improved in expression by more than twofold. The developed toolbox serves as a platform to tune P450 performance in microbial cells, thereby facilitating recombinant production of complex plant P450‐derived biochemicals. Biotechnol. Bioeng. 2017;114: 751–760. © 2016 Wiley Periodicals, Inc.
Mechanisms and therapeutic effectiveness of pulsed electromagnetic field therapy in oncology
Authors: Vadalà Maria , Morales‐Medina Julio Cesar , Vallelunga Annamaria , Palmieri Beniamino , Laurino Carmen , Iannitti Tommaso
Published: October 2016

Cancer is one of the most common causes of death worldwide. Available treatments are associated with numerous side effects and only a low percentage of patients achieve complete remission. Therefore, there is a strong need for new therapeutic strategies. In this regard, pulsed electromagnetic field (PEMF) therapy presents several potential advantages including non‐invasiveness, safety, lack of toxicity for non‐cancerous cells, and the possibility of being combined with other available therapies. Indeed, PEMF stimulation has already been used in the context of various cancer types including skin, breast, prostate, hepatocellular, lung, ovarian, pancreatic, bladder, thyroid, and colon cancer in vitro and in vivo. At present, only limited application of PEMF in cancer has been documented in humans. In this article, we review the experimental and clinical evidence of PEMF therapy discussing future perspectives in its use in oncology.
Observational study on quality of life, safety, and effectiveness of first‐line cetuximab plus chemotherapy in KRAS wild‐type metastatic colorectal cancer patients: the ObservEr Study
Authors: Pinto Carmine , Di Fabio Francesca , Rosati Gerardo , Lolli Ivan R. , Ruggeri Enzo M. , Ciuffreda Libero , Ferrari Daris , Lo Re Giovanni , Rosti Giovanni , Tralongo Paolo , Ferrara Raimondo , Alabiso Oscar , Chiara Silvana , Ianniello Giovanni P. , Frassoldati Antonio , Bilancia Domenico , Campanella Giovanna A. , Signorelli Carlo , Racca Patrizia , Benincasa Elena , Stroppolo Maria Elena , Di Costanzo Francesco
Published: October 2016

Cetuximab improves efficacy when added to chemotherapy for metastatic colorectal cancer (mCRC). Effective management of skin reactions from cetuximab improves quality of life (QoL), and treatment compliance in clinical trials. No data are available from real‐world settings. The ObservEr observational, multicenter, prospective study evaluated QoL, the incidence of skin reactions, and management of chemotherapy plus cetuximab in first‐line for mCRC. The primary endpoint was QoL measured with the Dermatology Life Quality Index (DLQI) and EORTC QLQ‐C30. Secondary endpoints were the incidence of skin and serious adverse events, median overall and progression‐free survival, tumor response, and resection rates. Between May 2011 and November 2012, 228 patients with KRASwt mCRC were enrolled at 28 Italian centers, 225 evaluable, median age 65 years. QoL did not change during treatment and was not affected by the choice of prophylactic or reactive skin management. The incidence of cetuximab‐specific grade ≥3 skin reactions was 14%, with no grade 4/5 events. Skin reactions correlated with survival (P = 0.016), and their incidence was influenced by chemotherapy regimen (oxaliplatin vs. irinotecan—Incidence rate ratio [IRR] 1.72, P < 0.0001) and gender (male vs. female—IRR 1.38, P = 0.0008). Compliance at first postbaseline evaluation was 97.75%. Median overall survival was 23.6 months, median progression‐free survival 8.3 months. Cetuximab plus chemotherapy did not compromise QoL in the routine clinical setting when patients receive close monitoring plus prophylactic or reactive management of skin reactions. We observed the same correlation between overall survival (OS) and skin reactions reported in controlled clinical trials, also in this setting.
Metformin induces degradation of mTOR protein in breast cancer cells
Authors: Alalem Mohamed , Ray Alpana , Ray Bimal K.
Published: October 2016

Activation of mTOR is implicated in the development and progression of breast cancer. mTOR inhibition exhibited promising antitumor effects in breast cancer; however, its effect is compromised by several feedback mechanisms. One of such mechanisms is the upregulation of mTOR pathway in breast cancer cells. Despite the established role of mTOR activation in breast cancer, the status of total mTOR protein and its impact on the tumor behavior and response to treatment are poorly understood. Besides, the mechanisms underlying mTOR protein degradation in normal and cancer breast cells are still largely unknown. We and others found that total mTOR protein level is elevated in breast cancer cells compared to their nonmalignant counterparts. We have detected defective proteolysis of mTOR protein in breast cancer cells, which could, at least in part, explain the high level of mTOR protein in these cells. We show that metformin treatment in MCF‐7 breast cancer cells induced degradation of mTOR and sequestration of this protein in a perinuclear region. The decrease in mTOR protein level in these cells correlated positively with a concomitant inhibition of proliferation and migration potentials of these cells. These findings provided a novel mechanism for the metformin action in breast cancer treatment. Understanding the proteolytic mechanism responsible for mTOR level in breast cancer may pave the way for improving the efficacy of breast cancer treatment regimens and mitigating drug resistance as well as providing a basis for potential novel therapeutic modalities for breast cancer.
Awareness and knowledge of Human Papillomavirus (HPV), HPV‐related cancers, and HPV vaccines in an uninsured adult clinic population
Authors: Radecki Breitkopf Carmen , Finney Rutten Lila J. , Findley Victoria , Jacobson Debra J. , Wilson Patrick M. , Albertie Monica , Jacobson Robert M. , Colón‐Otero Gerardo
Published: October 2016

Human papillomavirus (HPV) vaccines offer primary prevention of cervical cancer and protection against other HPV‐associated cancers. HPV vaccine coverage in the United States (U.S.) remains low, particularly among older adolescents/young adults, and the uninsured. We assessed awareness and knowledge of HPV disease, HPV‐related cancers, and HPV vaccines among working, uninsured adults. Data from the 2014 Health Information National Trends Survey (HINTS 4, Cycle 4) were used as a benchmark. Patients were surveyed in late 2014 at the Volunteers in Medicine free clinic in Duval County, Florida. Surveys contained validated measures of HPV disease and vaccine knowledge; HPV‐related cancer knowledge was also assessed. Two‐hundred and ninety‐six surveys were analyzable with an 84% participation rate. Half (50.3%) of participants had heard of HPV, and 32.1% had heard of the HPV vaccine; in HINTS, these estimates were 63.6% and 62.7%, respectively (both P < 0.0001). In adjusted models, high HPV disease knowledge was associated with white race and increased education; high vaccine knowledge was associated with white race, increased education, and female sex. Recognition of HPV as a causative agent was 43.9% for cervical, 9.1% for anal, and 11.1% for throat cancers. For all HPV‐associated cancers, participants had lower knowledge/recognition relative to HINTS. The uninsured, socioeconomically disadvantaged adults we surveyed were unaware of a ubiquitous virus that can cause cancer and the existence of a vaccine to protect against it. These findings point to settings and populations in which initiatives to promote HPV vaccination as a cancer prevention tool remain critical.
Serum miR‐221 serves as a biomarker for Parkinson's disease
Authors: Ma Wenbin , Li Yingying , Wang Chao , Xu Fan , Wang Meiling , Liu Yiming
Published: October 2016

Parkinson's disease (PD) is the common age‐related neurodegenerative disorder. Sensitive, noninvasive biomarkers that facilitate PD diagnosis and stage assignment are currently unavailable. This study aims to investigate the potential of 16 previous reported PD‐associated miRNAs as novel biomarkers for PD. The expression of 16 serum miRNAs was measured by quantitative reverse transcriptase polymerase chain reaction in 138 PD patients and 112 control populations. Analyses were undertaken to assess the specificity and sensitivity of miRNAs to predict PD. In addition, the relationship between deregulated miRNAs and Part III of the United Parkinson's Disease Rating Scale (UPDRS‐III) and Part V of the UPDRS (UPDRS‐V; the modified Hoehn and Yahr staging of PD) in PD patients was also assessed. It was found that the serums miR‐29c, miR‐146a, miR‐214, and miR‐221 were significantly decreased in PD patients compared with healthy control populations. In addition, serum miR‐221 was positively correlated with UPDRS‐III (r = .4702) and UPDRS‐V (r = .4788) score in PD patients. Furthermore, the receiver operating characteristic result of serum miR‐221 for prediction of PD was 0.787. Our preliminary findings indicate that downregulated serum miR‐221 might be a potential biomarker for PD evaluation.
Natural and Synthetic Macrocyclic Inhibitors of the Histone Deacetylase Enzymes
Authors: Maolanon Alex R. , Kristensen Helle M. E. , Leman Luke J. , Ghadiri M. Reza , Olsen Christian A.
Published: October 2016

Inhibition of histone deacetylase (HDAC) enzymes has emerged as a target for development of cancer chemotherapy. Four compounds have gained approval for clinical use by the Food and Drug Administration in the US, and several are currently in clinical trials. However, none of these compounds possesses particularly good isozyme selectivity, which would be a highly desirable feature in a tool compound. Whether selective inhibition of individual HDAC isozymes will provide improved drug candidates remains to be seen. Nevertheless, it has been speculated that using macrocyclic compounds to target HDAC enzymes might hold an advantage over the use of traditional hydroxamic‐acid‐containing inhibitors, which rely on chelation to the conserved active‐site zinc ion. Here we review the literature on macrocyclic HDAC inhibitors obtained from natural sources and on structure–activity relationship studies inspired by these molecules, as well as on efforts aimed at fully synthetic macrocyclic HDAC inhibitors.
Rational Design of a Polyoxometalate Intercalated Layered Double Hydroxide: Highly Efficient Catalytic Epoxidation of Allylic Alcohols under Mild and Solvent‐Free Conditions
Authors: Li Tengfei , Wang Zelin , Chen Wei , Miras Haralampos N. , Song Yu‐Fei
Published: October 2016

Intercalation catalysts, owing to their modular and accessible gallery and unique interlamellar chemical environment, have shown wide application in various catalytic reactions. However, the poor mass transfer between the active components of the intercalated catalysts and organic substrates is one of the challenges that limit their further application. Herein, we have developed a novel heterogeneous catalyst by intercalating the polyoxometalate (POM) of Na9LaW10O36⋅32 H2O (LaW10) into layered double hydroxides (LDHs), which have been covalently modified with ionic liquids (ILs). The intercalation catalyst demonstrates high activity and selectivity for the epoxidation of various allylic alcohols in the presence of H2O2. For example, trans‐2‐hexen‐1‐ol undergoes up to 96 % conversion and 99 % epoxide selectivity at 25 °C in 2.5 h. To the best of our knowledge, the Mg3Al−ILs−C8−LaW10 composite material constitutes one of the most efficient heterogeneous catalysts for the epoxidation of allylic alcohols (including the hydrophobic allylic alcohols with long alkyl chains) reported so far.
Reengineering Antibiotics to Combat Bacterial Resistance: Click Chemistry [1,2,3]‐Triazole Vancomycin Dimers with Potent Activity against MRSA and VRE
Authors: Silverman Steven M. , Moses John E. , Sharpless K. Barry
Published: October 2016

Vancomycin has long been considered a drug of last resort. Its efficiency in treating multiple drug‐resistant bacterial infections, particularly methicillin‐resistant Staphylococcus aureus (MRSA), has had a profound effect on the treatment of life‐threatening infections. However, the emergence of resistance to vancomycin is a cause for significant worldwide concern, prompting the urgent development of new effective treatments for antibiotic resistant bacterial infections. Harnessing the benefits of multivalency and cooperativity against vancomycin‐resistant strains, we report a Click Chemistry approach towards reengineered vancomycin derivatives and the synthesis of a number of dimers with increased potency against MRSA and vancomycin resistant Enterococci (VRE; VanB). These semi‐synthetic dimeric ligands were linked together with great efficiency using the powerful CuAAC reaction, demonstrating high levels of selectivity and purity.
Optimization of a spectrally tunable LED daylight simulator
Authors: Wei Minchen , Yang Biao , Lin Yandan
Published: October 2016

Daylight simulators (i.e., D50, D55, D65, and D75 simulators) play an important role for industrial applications, such as surface color industry, recipe formulation, and graphic arts industry. Conventional light sources, including xenon lamps, tungsten‐halogen lamps, and fluorescent lamps, have been used as daylight simulators. In this article, a genetic algorithm is employed to investigate optimized channels for each daylight simulator. It is found that at least six LED channels are required to produce high quality daylight simulators in terms of the CIE Metamerism Indices. Furthermore, it is possible to create a spectrally tunable daylight simulator using six LED channels with wavelengths of 357, 420, 474, 533, 595, and 660 nm. This wavelength combination with appropriate intensity combinations can produce D50, D55, D65, and D75 simulators with good performance, in terms of the CIE Metamerism Indices. The color appearance of various color samples or objects under such a daylight simulator is found to be very similar to those under a corresponding daylight illuminant. © 2016 Wiley Periodicals, Inc. Col Res Appl, 42, 419–423, 2017
Universal Diffraction of Atomic and Molecular Matter‐Waves: A Comparison of He and D2 Quantum Reflected from a Grating
Authors: Zhang Weiqing , Lee Ju Hyeon , Kim Hye Ah , Jin Byung Gwun , Kim Bong Jun , Kim Lee Yeong , Zhao Bum Suk , Schöllkopf Wieland
Published: October 2016

Molecular beams of He and D2 are scattered from a ruled diffraction grating in conical‐mount geometry under grazing‐incidence conditions. Fully resolved diffraction patterns as a function of detection angle are recorded for different grating azimuth angles and for two different kinetic energies of the particle beams. Variations in diffraction peak widths are traced back to different velocity spreads of He and D2 determined by time‐of‐flight measurements. A comprehensive analysis of diffraction intensities confirms universal diffraction, that is, for identical de Broglie wavelengths, the relative diffraction intensities for He and D2 are the same. Universal diffraction results from peculiarities of quantum reflection of the atoms and molecules from the diffraction grating. In quantum reflection particles scatter many nanometers in front of the surface from the long‐range attractive branch of the particle–surface interaction potential without probing the potential well and the short‐range repulsive branch of the potential.
Influence of atrial fibrillation on post‐discharge natriuretic peptide trajectory and clinical outcomes among patients hospitalized for heart failure: insights from the ASTRONAUT trial
Authors: Greene Stephen J. , Fonarow Gregg C. , Solomon Scott D. , Subacius Haris P. , Ambrosy Andrew P. , Vaduganathan Muthiah , Maggioni Aldo P. , Böhm Michael , Lewis Eldrin F. , Zannad Faiez , Butler Javed , Gheorghiade Mihai ,   for the ASTRONAUT Investigators and Coordinators
Published: October 2016

Aims

Change in NT‐proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear.

Methods and results

This analysis included 1358 patients from the ASTRONAUT trial, which randomized patients hospitalized for HF with EF ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of AFF on baseline ECG. NT‐proBNP was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months. Compared with non‐AFF patients, AFF patients experienced greater reduction from baseline in log‐transformed NT‐proBNP (interaction P < 0.001), but this difference was not significant after adjustment (interaction P = 0.726). The ability of aliskiren to lower NT‐proBNP during follow‐up differed by AFF status (interaction P = 0.001), with aliskiren lowering NT‐proBNP more than placebo among non‐AFF patients only. After adjustment, baseline AFF was not associated with mortality or HF hospitalization at 12 months (all P ≥ 0.152).

Conclusion

In this hospitalized HF cohort, AFF status did not influence post‐discharge NT‐proBNP trajectory or clinical outcomes after adjustment for patient characteristics. Aliskiren lowered follow‐up NT‐proBNP levels in patients without AFF, but had no influence among patients with AFF. This study generates the hypothesis that the ability of a HF trial to meet an NT‐proBNP defined endpoint may be influenced by the prevalence of AFF in the population. Because aliskiren did not improve outcomes in patients without AFF, this analysis suggests changes in NT‐proBNP induced by investigational therapies may be dissociated from clinical effects.
1‐Fluoro‐2,4‐dinitrobenzene and its derivatives act as secretagogues on rodent mast cells
Authors: Manabe Yohei , Yoshimura Marie , Sakamaki Kazuma , Inoue Asuka , Kakinoki Aya , Hokari Satoshi , Sakanaka Mariko , Aoki Junken , Miyachi Hiroyuki , Furuta Kazuyuki , Tanaka Satoshi
Published: October 2016

Accumulating evidence suggests that activated mast cells are involved in contact hypersensitivity, although the precise mechanisms of their activation are still not completely understood. We investigated the potential of common experimental allergens to induce mast cell activation using murine bone marrow‐derived cultured mast cells and rat peritoneal mast cells. Among these allergens, 1‐chloro‐2,4‐dinitrobenzene and 1‐fluoro‐2,4‐dinirobenzene (DNFB) were found to induce degranulation of rat peritoneal mast cells. DNFB‐induced degranulation is accompanied by cytosolic Ca2+ mobilization and is significantly inhibited by pertussis toxin, U73122 (a phospholipase C inhibitor), and BAPTA (a Ca2+ chelator), raising the possibility that DNFB acts on the G protein‐coupled receptors and activates Gi, which induces activation of phospholipase C, as well as known mast cell secretagogues, such as compound 48/80. DNFB could induce mast cell degranulation in the absence of serum proteins and IgE. Structure‐activity relationship analyses revealed an inverse correlation between the degree of degranulation and the electron density of the C1 carbon of the DNFB derivatives. These findings raise a possibility that DNFB functions as a potent contact allergen through induction of cutaneous mast cell degranulation.
Organometallic Nucleoside Analogues: Effect of Hydroxyalkyl Linker Length on Cancer Cell Line Toxicity
Authors: Kedge Jonathan L. , Nguyen Huy V. , Khan Zahra , Male Louise , Hodges Media K. Ismail, Holly V. Roberts, Nikolas J. , Horswell Sarah L. , Mehellou Youcef , Tucker James H. R.
Published: October 2016

A new series of chiral ferrocene derivatives containing both a hydroxyalkyl group and a thyminyl group on one cyclopentadienyl ring have been synthesised to probe structure–activity relationships in cancer cell line cytotoxicities. The stereoisomers of enantiomeric pairs of these so‐called ferronucleosides have been studied and characterised by a combination of chiral analytical HPLC and single‐crystal X‐ray diffraction. Biological activity studies revealed that changing the length of the hydroxyalkyl group had marked effects on IC50 values, with compounds having shorter arms that more closely resemble endogenous nucleosides exhibiting lower cytotoxicities. The lipophilicities and electrochemical properties of this compound series have been studied to rationalise these trends and indicate future directions of study.