bluuebunny/crossref_metadata_2025 huggingface dataset:
Writing a Publishable Paper – Principles, Questions, Realities, and Stumbling Blocks
Authors: Caldwell Cam
Published: April 2018

Purpose: This paper identifies what business faculty, new PhDs, graduate students, practitioners, and other scholars can do to improve the likelihood of publishing their research in academic journals.Design/methodology/approach:  Despite the fact that well educated scholars are generally well informed about management principles and theories, the success rate for obtaining acceptance of papers submitted to academic journals is typically well below 50% -- with some journals rejecting up to 95% of papers submitted.Findings:  This paper identifies principles important to writing an academic paper, questions to address to ensure that those papers achieve a high standard, realities that impact the publishing process, and stumbling blocks to overcome to get a publication accepted.Originality/value: This article highlights the overlooked concept of flair factors in the selection process, identifies six factors that are vital for successful employee selection, suggests three tools to improve selection processes, and presents five propositions for practitioners and scholars.
Reviewer Acknowledgements for International Business Research, Vol. 11, No. 5
Authors: Duran Kevin
Published: April 2018

International Business Research wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal are greatly appreciated.International Business Research is recruiting reviewers for the journal. If you are interested in becoming a reviewer, we welcome you to join us. Please find the application form and details at http://recruitment.ccsenet.org and e-mail the completed application form to ibr@ccsenet.org.Reviewers for Volume 11, Number 5 Abderrazek Hassen Elkhaldi, University of Sousse, TunisiaAnna Paola Micheli, Univrtsity of Cassino and Southern Lazio, ItalyAurelija Burinskiene, Vilnius Gediminas Technical University, LithuaniaCelina Maria Olszak, University of Economics in Katowice, PolandFawzieh Mohammed Masad, Jadara University, JordanFederica De Santis, University of Pisa , ItalyFevzi Esen, Istanbul Medeniyet University, TurkeyFilomena Izzo, University of Campania Luigi Vanvitelli, ItalyFlorin Ionita, The Bucharest Academy of Economic Studies, RomaniaFrancesco Ciampi, Florence University, ItalyFrancesco Scalera, University of Bari "Aldo Moro", ItalyGrzegorz Zasuwa, The John Paul II Catholic University of Lublin, PolandHanna Trojanowska, Warsaw University of Technology, PolandHung-Che Wu, Nanfang College of Sun Yat-sen University, ChinaImran Riaz Malik, IQRA University, PakistanJorge Mongay-Hurtado, ESIC Business and Marketing School, SpainKaren Gulliver, Argosy University, Twin Cities, USAM. Muzamil Naqshbandi, University of Dubai, UAEMaria do Céu Gaspar Alves, University of Beira Interior, PortugalMaurizio Rija, University of Calabria, ItalyMihaela Simionescu, Institute for Economic Forecasting of the Romanian Academy, RomaniaModar Abdullatif, Middle East University, JordanMohamed Abdel Rahman Salih, Taibah University, Saudi ArabiaMohamed Rochdi Keffala, University of Kairouan, TunisiaMuath Eleswed, American University of Kuwait, USAMurat Akin, Omer Halisdemir University FEAS – NIGDE, TurkeyÖzcan IŞIK, Cumhuriyet University, TurkeyPascal Stiefenhofer, University of Brighton, UKProsper Senyo Koto, Dalhousie University, CanadaRadoslav Jankal, University of Zilina, SlovakiaRiccardo Cimini, University of Tuscia, Viterbo, ItalyRoberto Campos da Rocha Miranda, University Center Iesb, BrazilShun Mun Helen Wong, The Hong Kong Polytechnic University, Hong KongValeria Stefanelli, University of Salento, ItalyVincent Grèzes, University of Applied Sciences Western Switzerland (HES-SO Valais-Wallis), SwitzerlandWanmo Koo, Western Illinois University, USAWing-Keung Wong, Asia University, Taiwan, China
The Misreading on Norman Levine’s Continuity of Marx and Hegel’s Thinking
Authors: Hao Baoquan
Published: April 2018

Norman Levin is an American Marxist expert who is famous for objecting to Engels, and he recently comes up with an idea related to the Marx and Engels' comment on continuity of ideology and method, especially, Hegel is the first Marxian judgment. However, Levine's statement and demonstration on that point where there is not only the confusion of the concept, the contradiction of the text and the confusion of the semantics, but also it fabricates information in the text, disserts the meaning of Marxian text to prove his false point. Levine's research method in the western Marxism studies is not the only case.
Selected Aspects of Professional
Functioning of Employees with Varied
Levels of Hope
Authors: Wołpiuk‑Ochocińska Anna
Published: April 2018

Managers face the challenge of identifying positive factors that form employees’ attitu‑
des and consequently play a decisive role in achieving a higher level of efficiency in the
form of employees’ work engagement and more effective realization of organizational
goals. The study involved 295 people employed in the Podkarpackie Province, surveyed
with the Snyder’s Adult Hope Questionnaire developed by M. Łaguna, J. Trzebiński and
M. Zięba, W.B. Schaufeli and A.B. Bakker’s UWES Questionnaire, and the Functioning at
Work Questionnaire developed for the purposes of the study. Employees with a high level
of hope declare better relations at work, higher efficiency and openness to change. The
results suggest that the impact of hope on job performance is in great part mediated by
work engagement, therefore personality traits related to hope should be considered in the
management of employees’ work engagement.
Various Features of Organizational Structures and Employability in Selected Public Organizations
Authors: Strużyna Janusz , Marzec Izabela
Published: April 2018

The relation of human resource management to the structural dimension of an organisation has aroused interest of researchers for a  long time. The organisational structure creates conditions for HRM, it describes allocation of tasks and responsibilities, determines the applied HRM tools, and as a result, it also decides about possibilities of employability enhancement in an organisation. This paper attempts to answer the question: what is the relationship between certain features of organisational structures and employability of public organisations’ employees.  This aim will be achieved by presenting the results of empirical research concerning features of organisational structures and their ties with employability of employees carried out in labour offices, social welfare centres and municipal offices.
Did Subsidy Depend on the Performance of Higher Education Institutions in Poland? Comparative study
Authors: Kalinowski Sławomir
Published: April 2018

Since early 1990s the system of financing higher education institutions in Poland is based on the algorithm which binds the value of subsidy also with the performance. It is basically depended on the number and the structure of the students and scientific staff, but within the past years new factors have been introduced: grants acquisition and internationalization. The goal of the article is to verify to what extent the value of the subsidy depended on the performance of the universities. The test produced the positive outcome for the universities of life sciences and universities of economics, which were outstanding for the statistically significant change of the index.
“Medium is the message” – Creating a University Image in the Time of Web 2.0
Authors: Koszembar‑Wiklik Małgorzata
Published: April 2018

The starting point of the article is McLuhan’s statement that “medium is the message”. The way universities promote themselves in media is causing specific associations with recipients.  The university idea is changing, the requirement for entrepreneurship, the change in the way of the public universities funding, and the corporate approach to university force them to take action that will enable them to operate in a highly competitive market. The universities promote and build their image using mass media characteristic for business marketing, and at the same time, the media that reach young people – the social media.
From Reducing Uncertainty to Dealing with Uncertainty. Change of Function of Organizational Culture
Authors: Sikorski Czesław
Published: April 2018

Theme of this article is change of organizational culture functions as result exchange epoch civilization from industrial to informatics. The change of understanding integration, perception and adaptation culture functions means that main cultural function in informatics epoch isn’t reduction of uncertainty but the help to manage of uncertainty. The need of high tolerance of uncertainty cause that organizational leaders should force to developing competence of subordinates to managing of uncertainty buy special educational events. In the article to this competences counted: emotional intelligence, extended perception and skills of dialog conducting.
Сфера поширення напівпредикативного синтаксичного зв’язку
Authors: Kobczenko Natalia
Published: April 2018

The paper deals with the analysis of syntactic connection between unattached phrases
(with characterizing semantics, but without detailing semantics) and the structure of the
basic sentence. The author proves that various structural-semantic types of unattached
phrases have diff erent grammatical ways of connection with the basic sentence. The semipredicative
syntactic connection occurs between an unattached component of properlyattribute
semantics and any substantive of the basic sentence. Unattached adverbial modifiers
and also unattached attributes of attribute-adverbial semantics and unattached
appositions of characterizing-adverbial semantics join the predicative centre of the basic
sentence with the determinative subordinate syntactic connection. And the syntactic connection
in sentences with an unattached adjective component of dual-predicate (predicative
attribute, duplexes) is a transitional between unitary and dual types.
Архаїчні ойконіми на *-ьskъ: Правобережне Полісся (ХХ –XХI ст.)
Authors: Kupczyńska Zoriana
Published: April 2018

The article is devoted to the analysis of geographical names ending in *-ьskъ of Right-
Bank Polissia in XX–XXI centuries. The author points out that oykonyms of this part of
Polissia have peculiarities in their structure and meanings of their creating stems. Moreover,
the author defi nes the chronology and the productivity of onyms of this type and characterizes
coordinates of expanse of geographical names ending in *-ьskъ on the territory of Right-
Bank Polissia during XX–XXI centuries.
Вплив ідеології на мову, мовознавство і мовознавців: штрихи до образу
українського суспільства першої третини XX ст.
Authors: Maciuk Halyna
Published: April 2018

The article provides insight into some new aspects of language situation and language
policy of the period under discussion. The author examines 1) the political and legislative
level of resolving the linguistic question in the context of national revival ideology in
1917–1922; 2) the ideology of Soviet construction (since 1922) and the distinctive features
of Ukrainisation; 3) the directions of linguistic studies and their development; 4) the political
motives behind the destruction of the Ukrainian linguistic science through discrediting
and repressing linguists.
Лінгвокогнітивна інтерпретація алегорії в українському художньому тексті
(з англійськими паралелями)
Authors: Monastyrska Chrystyna
Published: April 2018

The article describes the allegory characteristics as a conceptual and structural linguistic
phenomenon. The author determines peculiarities of its realization in the artistic text
and introduces the "allegory" concept. Allegorical structures are investigated as polyvalent
components of image forming as well as a means of encoding and transformation of
knowledge.
Antroponimia mieszczańska na obszarach kontaktowych polsko-ukraińskich
w XVI–XVII wieku
Authors: Mytnik Irena
Published: April 2018

This paper is devoted to a discussion of the anthroponymy of burghers in the former
Chelmia territory. It presents naming patterns used among Polish and Ukrainian people.
The most important issues discussed in this paper are as follows:
− a presentation and characteristics of naming styles using ele ments after the fi rst
name which refer to men, with an indication of the frequency of the suffi xes;
− the similarities and dissimilarities between Ukrainian and Polish anthroponymy
in olden day, the scope of mutual interference between the Polish and Ukrainian
lan guages and diff erent anthroponymic systems.
Materials for this paper are composed of archival and prints sources.
Образ коханої в любовній ліриці Спиридона Черкасенка
Authors: Czuj Andrij
Published: April 2018

Beloved woman’s character in Spyridon Cherkasenko’s love lyric

This article focuses on the character of a lyrical hero’s beloved woman. The present study analyzes the features of her appearance and character. It reveals the fact that the author presents only some single details of the portrait with the main focus on the woman’s eyes and lips. To expand the portrait, the author compares her beauty with the beauty of nature. We learn that the character of the beloved woman is changeful but, at the same time, strong and attractive for the lyrical hero. A research shows the meaning of a number of associative images in which the girl appears to the loving man. A little less attention is paid to other personifi cated characters who are witnesses and accomplices of the love stories. The author of this article concludes that landscape is not a mere background, but also an important acting character, utterly depending on the lyrical hero’s mood.
Віктор Шульгач, Нариси з праслов’янської антропоніімії, ч. ІІІ, Київ 2016, 472 с.
Authors: Mytnik Irena
Published: April 2018

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Attenuation of earmuffs used simultaneously with safety spectacles in exposure to impulse noise
Authors: Kozłowski Emil , Młyński Rafał
Published: April 2018

Impulse noise is particularly hazardous to the hearing of exposed individuals. In many real-life scenarios, the only protective measure used to reduce the level of impulse noise is hearing protectors. These scenarios include firing ranges. Aside from hearing protectors, shooters use personal safety spectacles. The purpose of this paper was to determine the effect of the simultaneous use of earmuffs and safety spectacles on the sound attenuation of earmuffs during exposure to impact noise. The research was completed with the MIRE method and included the determination of sound attenuation changes in five different models of earmuffs, used simultaneously with three different models of safety spectacles and prescription glasses. The impulse noise source used was a starting pistol, which generated C-weighted peak sound pressure level at a mean of 136.7 dB. The tests demonstrated that the simultaneous use of safety spectacles and earmuffs reduces the impulse noise attenuation of the earmuffs by up to 9 dB. Such sound attenuation changes occurred during simultaneous use of earmuffs with safety spectacles, which feature temples with a rectangular cross-section. The tests also demonstrated that the effect of prescription glasses on sound attenuation was unusually high; prescription glasses reduced the impulse sound attenuation of earmuffs by as much as 18 dB. Keywords: acoustics, noise protection, impulse noise, hearing protectors, earmuffs, noise attenuation
Treatment strategy of allergic rhinitis in the face of modern world threats
Authors: Rapiejko Piotr , Jurkiewicz Dariusz , Pietruszewska Wioletta , Zielnik-Jurkiewicz Beata , Woroń Jarosław , Lipiec Agnieszka
Published: April 2018

Allergic rhinitis (AR) is the most common form of allergy, which - as epidemiological research has shown - applies
to nearly 25% of the population. AR significantly affects the quality of life of the patient, and the more severe the
disease, the greater the risk of developing bronchial asthma. One of the factors affecting the severity of symptoms
and the degree of their control is air pollution. In some patients, despite proper treatment, persistence or only partial
remission of symptoms (uncontrolled allergic rhinitis) is observed. This can lead to an increase in comorbidities
- inflammation of the paranasal sinuses, otitis media and asthma - both in children and in adults. The treatment of
allergic rhinitis, in accordance with the standards, consists in: education of the patient, elimination of the allergen
from the environment and factors intensifying the course of the disease, selection of proper pharmacotherapy and
specific allergen immunotherapy. Many factors influence the selection of the antihistamine used, e.g., the opportunity
of safe increase of the dosage.
Theoretical predictions on the influence of moisture on movements of wooden construction elements
Authors: Grobelny Piotr , Dornowski Wojciech
Published: April 2018

The paper presents a method for determining the creep function of wood. A key feature of this method is a constitutive relation which includes the continuous effect of wood moisture on creep. The method can be applied to improve the precision of design of wooden structures as well to assess the safety of biodegraded (biologically corroded) structural elements fabricated from wood. Keywords: construction, wooden constructions, rheology, constitutive relation, creep function
Antimicrobial Potential of Endophytes from Datura metel Linn.
Authors: M. Madhu Priya , Simiyon Theoder P. Agastian
Published: April 2018

Endophytes are a suite of microorganisms that grow in the tissues of higher plants. Endophytes constitute a valuable source of secondary metabolites for the discovery of new potential therapeutic drugs.  Endophytes can have many effects on their host such as enhancement of stress, insect and disease resistance, and herbicide activities when in association with their host plant. The present study was to examine the antimicrobial activity of ethyl acetate extracts of endophytic fungi (both extra and intracellular) and actinomycete from the stem and root of Datura metel L. The crude extract of these endophytic isolates were screened for their antimicrobial potential. Among the endophytes, the extracellular fungal extract showed the highest antimicrobial activity when compared to intracellular fungi and actinomycetes. The studies and isolation of these compounds can be used as a good approach to search of novel products.
Antiviral potential of mangiferin against poliovirus
Authors: Zendrini Rechenchoski Daniele , Faccin-Galhardi Ligia Carla , Pacheco Cunha Arcelina , Pontes Silva Ricardo Nágila Maria , Nozawa Carlos , Carvalho Linhares Rosa Elisa
Published: April 2018

Poliovirus (PV),an enterovirus of the Picornaviridae family, is the agent of poliomyelitis, a devastating neurologic disease that may result in paralysis and even death.Mangiferin is the major constituent of Mangifera indica and has multiple pharmacological activities, including antiviral. This study evaluated the activity of mangiferin against poliovirus type-1 (PV-1). The compound exhibited the 50% cytotoxic concentration (CC50) > 2000 μg/mL in HEp-2 cell cultures, by the dimethylthiazolyl-diphenyltetrazolium bromide method (MTT). The 50% inhibitory concentration (IC50) was of 53.5 μg/mL, determined by the plaque reduction assay (PRA) with selectivity index (SI) > 37.4. We investigate the possible mechanism of action of mangiferin and a maximum inhibition of PV was found for virucidal and inhibition of adsorption assays, at all tested concentrations. The inhibition of viral protein synthesis was also demonstrated by immunofluorescence assay (IFA).These results suggested that mangiferin is an attractive candidate for the control of PV infection.
The Function of Code-Switching in Selma Dabbagh’s Out of It
Authors: TawfiqHamamra Bilal , Qararia Salsabil
Published: April 2018

Bilingualism and biculturalism have a very immediate impact on the make-up of literary works of bilingual and bicultural authors with immediate linguistic traces of bilingual and bicultural mosaic of textual creation. Code-switching is a linguistic and cultural practice used by bilinguals in writing and speaking. This article examines the linguistic and cultural phenomenon of code-switching employed in Selma Dabbagh’s novel Out of It (2011). We argue that Dabbagh uses code-switching from English into Arabic so as to address the concerns of Palestinians and maintain her Palestinian belonging. At the very beginning, we explain what is meant by code-switching and briefly elucidate the reasons why bilingual authors use this technique. Thereafter, we shed light on the author’s background and expound the different types of code-switching she employs in Out of It. The upshot of this article clears up cultural and textual hybridity as the product of the application of code-switching.
Which Cultural Aspects do The Textbooks of Teaching Turkish to Foreigners Transfer?
Authors: BASKIN Sami
Published: April 2018

Teaching a foreign language aims at not only teaching the language and language skills, but transferring the culture of the target language. The main reason for that is people learn the target language as a standby in addition to learning the language. It is important that the more individuals learn the cultural features of the country the more they understand the language better. It is an undeniable fact that language and culture are inseparable parts, so culture should be learned simultaneously while learning that language. Because of that relationship between language and culture, language teaching also means teaching culture. Foreign language textbooks reflect the characteristics of the language-speaking community and make it a cultural product of that language. This study is to identify the place and importance of the textbooks used in teaching Turkish to foreigners in the target language teaching and to research which cultural items these books convey. Thus,  A1-A2 level textbooks of the Turkish teaching set for Gazi Foreigners were selected as a sample and done document analysis to identify what these sources include in terms of "daily life, interpersonal relations, values and education, literature-arts and music, traditions and folklore, social life, geography and space, foreign (universal) cultural elements". It was observed that the elements of Turkish culture concentrated on the relation between daily life and interpersonal relations, and there was no balanced distribution among other cultural elements. Therefore, these books need to be reviewed so that they can raise cultural awareness of the students.
A Meta-summary of the Research on Metaphors Regarding Turkish EFL Teachers’ Roles
Authors: Demir Yusuf
Published: April 2018

This meta-summary set out to provide an overarching comprehension of the metaphorical conceptualizations with regard to Turkish EFL teachers’ roles. Following the searches in a large number of international and national databases, and the setting of specific criteria for inclusion, eight research papers remained for investigation. The data analysis followed a theory-driven deductive approach to thematic analysis, by adopting the framework offered by Saban, Koçbeker and Saban (2006). After the transformation and standardization of the data sets in the related studies, it was found out that Turkish EFL teachers are most characterized by knowledge provider, and then facilitator/scaffolder roles. These are followed by nurturer/cultivator and archetype of spirit roles. Among the least associated roles with these teachers were superior authority figure, molder and agent of change. When intergroup differences of the perceptions are examined, ELT student teachers and English learners conceptualized Turkish EFL teachers mainly as knowledge provider followed by facilitator/scaffolder, whereas the teachers tended to assign themselves the role of a facilitator/scaffolder most, followed by leader, knowledge provider, and entertainer.
The Implementation of the 2012 Mental Health Strategy for Canada Through the Lens of FASD
Authors: Anderson Tara , Mela Mansfield , Stewart Michelle
Published: April 2018

It is the current authors’ perspective that the successful implementation of Changing Directions, Changing Lives, which seeks to improve mental health and well-being in Canada, cannot be realized effectively without considering FASD. Given that 94% of individuals with FASD also have mental disorders, practitioners in the mental health system are encountering these individuals every day. Most mental health professionals have not been trained to identify or diagnose FASD, and therefore it goes largely “unseen,” and individual treatment plans lack efficacy. Implementation of FASD-informed recommendations, such as those of the Truth and Reconciliation Commission of Canada (2015), can provide a more effective approach to mental health services and improve mental health outcomes.
Semiconductive Single Molecular Bilayers Realized Using Geometrical Frustration
Authors: Arai Shunto , Inoue Satoru , Hamai Takamasa , Kumai Reiji , Hasegawa Tatsuo
Published: April 2018

A unique solution‐based technology to manufacture self‐assembled ultrathin organic‐semiconductor layers with ultrauniform single‐molecular‐bilayer thickness over an area as large as wafer scale is developed. A novel concept is adopted in this technique, based upon the idea of geometrical frustration, which can effectively suppress the interlayer stacking (or multilayer crystallization) while maintaining the assembly of the intralayer, which originates from the strong intermolecular interactions between π‐conjugated molecules. For this purpose, a mixed solution of extended π‐conjugated frameworks substituted asymmetrically by alkyl chains of variable lengths (i.e., (πCore)‐Cn's) is utilized for the solution process. A simple blade‐coating with a solution containing two (πCore)‐Cn's with different alkyl chain lengths is effective to provide single molecular bilayers (SMBs) composed of a pair of polar monomolecular layers, which is analogical to the cell membranes of living organisms. It is demonstrated that the chain‐length disorder does not perturb the in‐plane crystalline order, but acts effectively as a geometrical frustration to inhibit multilayer crystallization. The uniformity, stability, and size scale are unprecedented, as produced by other conventional self‐assembly processes. The obtained SMBs also exhibit efficient 2D carrier transport as organic thin‐film transistors. This finding should open a new route to SMB‐based ultrathin superflexible electronics.
Flow behavior of PP‐polymer nanocomposites in injection molding hyperbolical dies
Authors: Mitsoulis Evan , Battisti Markus , Neunhäuserer Andreas , Perko Leonhard , Friesenbichler Walter
Published: April 2018

Nanocomposites based on layered silicates offer a remarkable potential in improving mechanical properties with filler loadings lower than 5%. For such polymer nanocomposites, it is important to improve intercalation and exfoliation of the silicate layers by finding the right balance between these effects. Previous works showed that intercalation and exfoliation can be influenced by the use of an additional, extensional flow which can be generated by hyperbolical dies used in the injection molding process. Since such hyperbolical dies account for high shear rates, additional pressure drop, and viscous dissipation, it is of high practical relevance to correctly predict the injection pressure needed. Besides conical geometries, hyperbolical die geometries are of importance due to their uniform elongational rate. Using hyperbolical dies having different diameters,D, and length‐to‐diameterL/Dratios, a full rheological characterization has been carried out for a polypropylene‐filled nanocomposite, and the experimental data have been fitted both with a viscous model (Cross) and a viscoelastic one (the Kaye—Bernstein, Kearsley, Zapas/Papanastasiou, Scriven, Macosko or K‐BKZ/PSM model). Four injection molding dies have been also used to reach apparent shear rates up to 500,000 s−1. Particular emphasis has been given on the pressure dependence of viscosity. It was found that only the viscoelastic simulations were capable of reproducing the experimental data well, while any viscous modeling always underestimates the pressures, especially at the higher apparent shear rates andL/Dratios.
Minimum energy of multicomponent distillation systems using minimum additional heat and mass integration sections
Authors: Jiang Zheyu , Madenoor Ramapriya Gautham , Tawarmalani Mohit , Agrawal Rakesh
Published: April 2018

Heat and mass integration to consolidate distillation columns in a multicomponent distillation configuration can lead to a number of new energy efficient and cost‐effective configurations. In this work, a powerful and simple‐to‐use fact about heat and mass integration is identified. The newly developed heat and mass integrated configurations, which we call as HMP configurations, involve first introducing thermal couplings to all intermediate transfer streams, followed by consolidating columns associated with a lighter pure product reboiler and a heavier pure product condenser. A systematic method of enumerating all HMP configurations is introduced. The energy savings of HMP configurations is compared with the well‐known fully thermally coupled (FTC) configurations. HMP configurations can have very similar and sometimes even the same minimum total vapor duty requirement as the FTC configuration is demonstrated, while using far less number of column sections, intermediate transfer streams, and thermal couplings than the FTC configurations. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3410–3418, 2018
Modification of ɛ‐poly‐L‐lysine in vivo to reduce self‐toxicity and enhance antibiotic overproduction
Authors: Ding Jin , Liang Hengyu , Fu Shuai , Liu Ran , Deng Zixin , Liu Tiangang
Published: April 2018

ɛ‐poly‐L‐lysine (ɛ‐PL) is a novel commercial food preservative, and glucose and glycerol are two carbon sources commonly used in ɛ‐PL fermentation. Using MALDI‐TOF and NMR, when grown in glycerol‐based medium, but not glucose‐based medium is determined, Streptomyces albulus J1‐005 produces a derivative of ɛ‐PL in which the terminal carboxyl group is modified with the second hydroxyl group of glycerol. Interestingly, this derivative, 2‐ɛ‐poly(L‐lys)‐glycerol, was hydrolyzed back to ɛ‐PL when the pH was adjusted from 3.7 to the neutral range. Antimicrobial assays indicated that, compared to ɛ‐PL, 2‐ɛ‐poly(L‐lys)‐glycerol has similar inhibitory activity against several bacterial species but is less inhibitory to the producing strain. Additionally, in fed‐batch fermentation, product yield was 37% higher in glycerol‐based medium than in medium containing an equal amount of glucose. Hence, we propose that such culture‐based approaches for modifying toxic compounds in vivo can be a promising strategy for antibiotic overproduction. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4187–4192, 2018
Feasibility, safety, and outcome of recanalization treatment in childhood stroke
Authors: Bigi Sandra , Dulcey Andrea , Gralla Jan , Bernasconi Corrado , Melliger Amber , Datta Alexandre N. , Arnold Marcel , Kaesmacher Johannes , Fluss Joel , Hackenberg Annette , Maier Oliver , Weber Johannes , Poloni Claudia , Fischer Urs , Steinlin Maja
Published: April 2018

Objective

Intravenous thrombolysis and endovascular therapy (IVT/EVT) are evidence‐based treatments for adults with arterial ischemic stroke (AIS). However, randomized controlled trials in pediatric patients are lacking. This study aimed to describe feasibility, safety, and outcome of IVT/EVT in children with AIS.

Methods

This retrospective study (01/2000–12/2015) included a multicenter, population‐based consecutive cohort of patients aged 1 month to 16 years, diagnosed with AIS and presenting with pediatric National Institutes of Health Stroke Scale (pedNIHSS) ≥ 4. Clinical and radiological data of patients receiving IVT/EVT were compared to those receiving standard care (SC) using linear regression to adjust for potential confounders. EVT included intra‐arterial thrombolysis and/or mechanical thrombectomy. Outcome was assessed 6 months after stroke using the pediatric stroke outcome measure (PSOM).

Results

Overall, 150 patients (age 7.1 ± 4.9 years, 55 [37%] females) presented with pedNIHSS ≥ 4. Recanalization treatment was performed in 16 (11%), of whom 5 (3%) were treated with IVT and 11 (7%) with EVT. Patients receiving recanalization treatment were older (mean age = 11.0 vs 6.9 years, p = 0.01) and more severely affected (median pedNIHSS = 13.5 vs 8.0, p < 0.001). Death and bleeding complications did not differ between the 2 groups. Median (interquartile range) PSOM 6 months after AIS was 2.5 (1–4.3) and 1 (0–2) in the IVT/EVT and SC groups, respectively (p = 0.014). However, after multiple linear regression analysis, only higher baseline pedNIHSS remained associated with an unfavorable outcome (p < 0.001).

Interpretation

Recanalization treatment is feasible and seems to be safe in severely affected pediatric AIS patients. The assessment of efficacy of IVT/EVT in pediatric stroke patients requires larger studies. Ann Neurol 2018;83:1125–1132
Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy
Authors: Winawer Melodie R. , Griffin Nicole G. , Samanamud Jorge , Baugh Evan H. , Rathakrishnan Dinesh , Ramalingam Senthilmurugan , Zagzag David , Schevon Catherine A. , Dugan Patricia , Hegde Manu , Sheth Sameer A. , McKhann Guy M. , Doyle Werner K. , Grant Gerald A. , Porter Brenda E. , Mikati Mohamad A. , Muh Carrie R. , Malone Colin D. , Bergin Ann Marie R. , Peters Jurriaan M. , McBrian Danielle K. , Pack Alison M. , Akman Cigdem I. , LaCoursiere Christopher M. , Keever Katherine M. , Madsen Joseph R. , Yang Edward , Lidov Hart G. W. , Shain Catherine , Allen Andrew S. , Canoll Peter D. , Crino Peter B. , Poduri Annapurna H. , Heinzen Erin L.
Published: April 2018

Objective

Somatic variants are a recognized cause of epilepsy‐associated focal malformations of cortical development (MCD). We hypothesized that somatic variants may underlie a wider range of focal epilepsy, including nonlesional focal epilepsy (NLFE). Through genetic analysis of brain tissue, we evaluated the role of somatic variation in focal epilepsy with and without MCD.

Methods

We identified somatic variants through high‐depth exome and ultra–high‐depth candidate gene sequencing of DNA from epilepsy surgery specimens and leukocytes from 18 individuals with NLFE and 38 with focal MCD.

Results

We observed somatic variants in 5 cases in SLC35A2, a gene associated with glycosylation defects and rare X‐linked epileptic encephalopathies. Nonsynonymous variants in SLC35A2 were detected in resected brain, and absent from leukocytes, in 3 of 18 individuals (17%) with NLFE, 1 female and 2 males, with variant allele frequencies (VAFs) in brain‐derived DNA of 2 to 14%. Pathologic evaluation revealed focal cortical dysplasia type Ia (FCD1a) in 2 of the 3 NLFE cases. In the MCD cohort, nonsynonymous variants in SCL35A2 were detected in the brains of 2 males with intractable epilepsy, developmental delay, and magnetic resonance imaging suggesting FCD, with VAFs of 19 to 53%; Evidence for FCD was not observed in either brain tissue specimen.

Interpretation

We report somatic variants in SLC35A2 as an explanation for a substantial fraction of NLFE, a largely unexplained condition, as well as focal MCD, previously shown to result from somatic mutation but until now only in PI3K‐AKT‐mTOR pathway genes. Collectively, our findings suggest a larger role than previously recognized for glycosylation defects in the intractable epilepsies. Ann Neurol 2018
Stabilization of epoxidized soybean oil‐plasticized poly(vinyl chloride) blends via thermal curing with genistein
Authors: Buddhiranon Sasiwimon , Chang Teng , Tang Kangli , Kyu Thein
Published: April 2018

In an effort to alleviate the well‐known toxicity effect of phthalate derivatives on human health, genistein (G) modified epoxidized soybean oil (ESBO) has been investigated as an alternative “green” plasticizer for poly(vinyl chloride) (PVC) with potential application in medical products. As evidenced by a single glass transition that shifts systematically with composition in conjunction with the melting point depression of G crystals, ESBO is not only a good plasticizer to PVC, but also miscible with G. Moreover, ESBO is an excellent compatibilizer to the immiscible PVC/G pair. Furthermore, PVC/ESBO/G ternary blends revealed complete miscibility in the amorphous state. Of particular interest is that ESBO‐plasticized PVC is thermally curable with G at elevated temperatures above 220 °C and affords relatively stable G modified ESBO‐plasticized PVC for blood contact medical applications such as blood bags and hemodialysis tubings. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46472.
Light‐Induced Bending of Needle‐Like Crystals of Naphthylvinylbenzoxazole Triggered by trans–cis Isomerization
Authors: Peng Jiang , Zhao Jinyu , Ye Kaiqi , Gao Hongqiang , Sun Jingbo , Lu Ran
Published: April 2018

New diarylethene derivatives containing benzoxazole (NBO) and benzothiazole (NBT) have been synthesized. Light‐induced trans–cis isomerization of NBO and NBT took place in crystals, and only induced the needle‐like crystals of NBO to bend backwards away from the UV light source. The movement of the atoms was deemed to take place during the isomerization of NBO; hence, strain would be produced and accumulated rapidly in the surface of crystals exposed to UV light. The uniform release of strain led to the bending of needle‐like crystals. The light‐induced trans–cis isomerization efficiency of NBT was too low to drive the motion of crystals, which might have originated from the large repulsion between naphthyl and benzothiazole. These results provide a new platform for the transformation of light energy into mechanical energy in molecular crystals through the unimolecular photochemical reaction of diarylethene derivatives.
Randomized, controlled study of bleselumab (ASKP1240) pharmacokinetics and safety in patients with moderate‐to‐severe plaque psoriasis
Authors: Anil Kumar Mysore S. , Papp Kim , Tainaka Ryo , Valluri Udaya , Wang Xuegong , Zhu Tong , Schwabe Christian
Published: April 2018

This study evaluated the pharmacokinetics (PK), efficacy, safety, and tolerability of bleselumab – a fully‐human anti‐CD40 monoclonal recombinant IgG4. Patients with moderate‐to‐severe psoriasis were randomized on day 1 to receive bleselumab or placebo on days 1, 15 and 29 in a dose‐escalation of bleselumab at 0.1, 0.3, 1.0 or 3.0 mg/kg. The safety‐analysis set (SAF) and full‐analysis set (FAS) included all patients who received bleselumab or placebo, and the PK‐analysis set (PKAS) included patients in the SAF with ≥1 quantifiable serum bleselumab concentration. Serial blood samples were collected after each dose, and the bleselumab serum concentration was measured. After each dose, the area‐under‐the‐concentration–time curve over 336 hours (AUC336) and the maximum serum concentration (Cmax), and dose proportionality of AUC336 and Cmax were determined. The psoriasis area and severity index (PASI) score, the physician static global assessment (PSGA) score, the percentage body surface area (%BSA) affected with psoriasis, adverse events and laboratory parameters were assessed. Sixty patients were randomized and included in the SAF/FAS (bleselumab, n = 49; placebo, n = 11); 48 formed the PKAS. Bleselumab Cmax and AUC336 were more than dose proportional in the range 0.1–3.0 mg/kg, suggesting nonlinear PK after single/multiple doses. No clinically significant infusion reactions, cytokine‐release syndrome, or thromboembolic events were reported. Bleselumab did not improve the PASI scores, PSGA scores, or %BSA versus placebo. Transient elevation of alanine aminotransferase and aspartate aminotransferase levels by >3 × upper limit of normal were observed in four (8.2%) and two (4.1%) patients, respectively, in the 1.0 or 3.0 mg/kg groups. Patients with liver function test increases had no concurrent changes in bilirubin. Bleselumab demonstrated nonlinear PK after single and multiple doses, with few adverse reactions.
Population pharmacokinetics of gliclazide in normal and diabetic rabbits
Authors: Shaik Mastan , Shaik Shabana , Kilari Eswar Kumar
Published: April 2018

Gliclazide is a second‐generation sulphonylurea drug widely used in the treatment of type 2 diabetes. However, there is no single report to describe the population pharmacokinetics of gliclazide in animal models. This study was aimed to evaluate the population pharmacokinetics (PK) of gliclazide in normal and alloxan‐induced diabetic rabbits using nonlinear mixed effects modeling. A total of 90 New Zealand white rabbits were administered with three doses (4.13, 8.27 and 16.53 mg/kg b.wt) of gliclazide by an oral route. Blood samples were collected up to 24 hr and the gliclazide concentrations in rabbit were determined using the HPLC method. The non‐compartmental and classical compartmental PK analyses were performed using Phoenix WinNonlin. Population PK analysis of gliclazide was performed using nonlinear mixed‐effects model software NONMEM and Phoenix NLME considering the weight, age, sex, health and dose as covariates. The final population values for clearance (CL), volume of distribution (V) and the absorption rate constant (ka) were 5270 ml/hr, 55700 ml and 0.708 hr−1, respectively. The inter‐individual variability in gliclazide CL, V and ka was 16.3%, 14.9% and 26.5%, respectively. There was no significant difference between NONMEM and Phoenix NLME pharmacokinetic results. The visual predictive check and bootstrap analysis confirmed the predictive ability, model stability and precision of the parameter estimates from this model. This population PK model demonstrated that gliclazide pharmacokinetics is best described by one‐compartment model with first‐order absorption in rabbits. Body weight is a covariate that significantly influences gliclazide kinetic disposition in rabbits.
High‐efficiency affinity precipitation of multiple industrial mAbs and Fc‐fusion proteins from cell culture harvests using Z‐ELP‐E2 nanocages
Authors: Swartz Andrew R. , Xu Xuankuo , Traylor Steven J. , Li Zheng Jian , Chen Wilfred
Published: April 2018

Affinity precipitation using Z‐elastin‐like polypeptide‐functionalized E2 protein nanocages has been shown to be a promising alternative to Protein A chromatography for monoclonal antibody (mAb) purification. We have previously described a high‐yielding, affinity precipitation process capable of rapidly capturing mAbs from cell culture through spontaneous, multivalent crosslinking into large aggregates. To challenge the capabilities of this technology, nanocage affinity precipitation was investigated using four industrial mAbs (mAbs A–D) and one Fc fusion protein (Fc A) with diverse molecular properties. A molar binding ratio of 3:1 Z:mAb was sufficient to precipitate >95% mAb in solution for all molecules evaluated at ambient temperature without added salt. The effect of solution pH on aggregation kinetics was studied using a simplified two‐step model to investigate the protein interactions that occur during mAb–nanocage crosslinking and to determine the optimal solution pH for precipitation. After centrifugation, the pelleted mAb–nanocage complex remained insoluble and was capable of being washed at pH ≥ 5 and eluted with at pH < 4 with >90% mAb recovery for all molecules. The four mAbs and one Fc fusion were purified from cell culture using optimal process conditions, and >94% yield and >97% monomer content were obtained. mAb A–D purification resulted in a 99.9% reduction in host cell protein and >99.99% reduction in DNA from the cell culture fluids. Nanocage affinity precipitation was equivalent to or exceeded expected Protein A chromatography performance. This study highlights the benefits of nanoparticle crosslinking for enhanced affinity capture and presents a robust platform that can be applied to any target mAb or Fc‐containing proteins with minimal optimization of process parameters.
Chemically controlled aggregation of pluripotent stem cells
Authors: Lipsitz Yonatan Y. , Tonge Peter D. , Zandstra Peter W.
Published: April 2018

Heterogeneity in pluripotent stem cell (PSC) aggregation leads to variability in mass transfer and signaling gradients between aggregates, which results in heterogeneous differentiation and therefore variability in product quality and yield. We have characterized a chemical‐based method to control aggregate size within a specific, tunable range with low heterogeneity, thereby reducing process variability in PSC expansion. This method enables controlled, scalable, stirred suspension‐based manufacturing of PSC cultures that are critical for the translation of regenerative medicine strategies to clinical products.
Pharmacokinetic properties of wogonin and its herb–drug interactions with docetaxel in rats with mammary tumors
Authors: Wang Ting , Long Fangyi , Jiang Gang , Cai Hong , Jiang Qian , Cheng Kai , Hu Zhiqiang , Wang Yuxi
Published: April 2018

Docetaxel, frequently used for the treatment of breast cancer, is mainly metabolized via hepatic cytochrome P450 (CYP) 3A in humans and is also a substrate of P‐glycoprotein (P‐gp). Wogonin has been shown to be able to modulate the activities of CYPs and P‐gp, and it could serve as an adjuvant chemotherapeutic agent. However, the impacts of co‐administration of wogonin and docetaxel on their pharmacokinetics have not been studied because of a lack of an analytical method for their simultaneous measurement. In the present study, we established an HPLC–MS/MS method for simultaneous measurement of wogonin and docetaxel in rat plasma, and it was then utilized to explore the pharmacokinetics of wogonin and the herb–drug interactions between wogonin and docetaxel after their combined administration in rats with mammary tumors. The rats received 10, 20 and 40 mg/kg wogonin via oral administration, with or without docetaxel intravenously administered at 10 mg/kg, and the plasma concentrations of wogonin and docetaxel were measured using the established and validated HPLC–MS/MS method. The Cmax and AUC0–t of wogonin were proportionally increased in the dose range from 10 to 40 mg/kg, suggesting a linear pharmacokinetics of wogonin. Moreover, the Cmax and AUC0–t of docetaxel and the AUC0–t of wogonin were increased after co‐administration (p < 0.05), indicating increased in vivo exposures of both wogonin and docetaxel, which might lead to an increase in not only therapeutic but also toxic effects. Thus the alterations of pharmacokinetics should be taken into consideration when wogonin and docetaxel are co‐administered.
The clitoral activation paradox — Claimed outcomes from different methods of its stimulation
Authors: Levin Roy J.
Published: April 2018

This article reviews clitoral structures, their functions and how they are activated during the stages of female life. The paradox that occurs is that different procedures of activation are claimed by some to favor ‘noxious outcomes’ to the physical and psychic health of women who use it to achieve sexual arousal/orgasm with or without penile vaginal intercourse. A number of the difficulties and inconsistencies in relation to these claims are explored. The proposed justification for the ‘noxious outcomes’ is that ‘evolution’ punishes sexual arousals other than by coitus because it is the only one that leads to gene propagation. In this context, however, the new, evolutionary interpretation of clitoral function in the fertile years as a fundamental proximate mechanism for facilitating female reproductive fitness makes such a justification improbable. The role of coital alignment technique (CAT) in the treatment of female orgasmic disorder is discussed in relation to its features of introital, clitoral and periurethral glans stimulation. Attempts to control female sexuality through various ‘clitoridectomies’ are examined, and unanswered questions about clitoral stimulation are listed. Clin. Anat. 31:650–660, 2018. © 2018 Wiley Periodicals, Inc.