bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saddle-Reset for Robust Parameter Estimation and Identifiability Analysis of Nonlinear Mixed Effects Models
Authors: Bjugård Nyberg Henrik , Hooker Andrew C. , Bauer Robert J. , Aoki Yasunori 
Published: July 2020

AbstractParameter estimation of a nonlinear model based on maximizing the likelihood using gradient-based numerical optimization methods can often fail due to premature termination of the optimization algorithm. One reason for such failure is that these numerical optimization methods cannot distinguish between the minimum, maximum, and a saddle point; hence, the parameters found by these optimization algorithms can possibly be in any of these three stationary points on the likelihood surface. We have found that for maximization of the likelihood for nonlinear mixed effects models used in pharmaceutical development, the optimization algorithm Broyden–Fletcher–Goldfarb–Shanno (BFGS) often terminates in saddle points, and we propose an algorithm, saddle-reset, to avoid the termination at saddle points, based on the second partial derivative test. In this algorithm, we use the approximated Hessian matrix at the point where BFGS terminates, perturb the point in the direction of the eigenvector associated with the lowest eigenvalue, and restart the BFGS algorithm. We have implemented this algorithm in industry standard software for nonlinear mixed effects modeling (NONMEM, version 7.4 and up) and showed that it can be used to avoid termination of parameter estimation at saddle points, as well as unveil practical parameter non-identifiability. We demonstrate this using four published pharmacometric models and two models specifically designed to be practically non-identifiable.
Of Emptiness and Revolution
Authors: Huang Yiju 
Published: July 2020

Abstract
Lu Xun 魯迅 (1881–1936) has remained a most prominent figure in modern Chinese literary studies, but not so in modern Buddhism scholarship. This article shows the interlacing of Lu Xun's revolutionary vision with Buddhism on three primary terrains: his indebtedness to his teacher Zhang Taiyan 章太炎 (1868–1936), his immersion in a wide range of Buddhist texts before the May Fourth movement, and a close reading of selected poems from Yecao 野草 (Wild Grass) in light of Buddhist philosophy. The author argues that Yogācāra conceptions promoted by Zhang, wanfa weixin 萬法唯心 (all phenomena are nothing but mind), bushi 佈施 (the bodhisattva ideal of sacrificial giving), and kong 空 (emptiness as boundless potentiality), greatly influenced Lu Xun's aesthetics. Ultimately, this article shows how revolution, the dominant mode of secularism, is theistically conditioned. The Buddhist notion of emptiness, rather than an impediment to modernity, informs the worldly action of revolution and the phenomenal possibility of change.
The Failure of the May Fourth Movement and My Two Struggles
Authors: Zaifu Liu , Guo Yijiao 
Published: July 2020

Abstract
In this speech, Liu Zaifu thoroughly discusses the history of the May Fourth movement and the New Culture movement in the whole last century and the circumstances of humanity in China. In his explanation, May Fourth could be conceptualized through three different groups of concepts: the cultural May Fourth and the political May Fourth, the New Culture movement and the New Literature movement, and the masculine May Fourth and the feminine May Fourth. Liu regards the May Fourth spirit as a complete failure, in terms of six symbolic signs: (1) the mass spiritual suicide of Guo Moruo and the Creation Society, (2) the failure of humanity, (3) the elimination of individuality and personality, (4) the reversal of the enlightenment subject, (5) the devastation of the world vision, and (6) the failure of aesthetic practice. Liu also shares his two struggles. The first struggle in the 1980s was to reconstruct the subjectivity and dignity of people. After going abroad, he started the second struggle in exiling the gods, by which he endeavored to free himself from the four major spiritual chains: revolutionary thinking, the idolatry of nation, all the political ideologies, and dualistic thinking.
“Standing Alone atop the Mountain, Walking Freely under the Sea”
Authors: Wang David Der-wei 
Published: July 2020

Abstract
Liu Zaifu is one of the most influential critics in the New Era after the Cultural Revolution. His works, such as On Literary Subjectivity (1985) and A Treatise of Character Composition (1986), inspired a generation of Chinese youth yearning for intellectual breakthroughs. After June 4, 1989, however, Liu's life took unexpected twists and turns. He exiled himself overseas, finally settling down in the United States. In the ensuing three decades, he has produced dozens of books, articles, and essays, some of which—including Farwell to Revolution (1995)—have become instant classics. However, in terms of personal engagement and reflective intensity, his forthcoming Five Autobiographical Accounts outstrips his other, prior work. This article seeks to describe Liu's intellectual and personal adventures in light of his autobiography. The year 2019 marks the thirtieth anniversary of the June Fourth democracy movement, as well as Liu's self-exile; the seventieth anniversary of the founding of the People's Republic of China (1949); and most important, the centennial of the May Fourth movement (1919). Juxtaposed against one another, these dates compel us to reflect on the high hopes and bitter outcomes, grand projects and failed expectations, that informed China's century-long pursuit of modernity.
Neural crest cells require Meis2 for patterning the mandibular arch via the Sonic hedgehog pathway
Authors: Fabik Jaroslav , Kovacova Katarina , Kozmik Zbynek , Machon Ondrej 
Published: July 2020

ABSTRACT
Cranial neural crest cells (cNCCs) originate in the anterior neural tube and populate pharyngeal arches in which they contribute to formation of bone and cartilage. This cell population also provides molecular signals for the development of tissues of non-neural crest origin, such as the tongue muscles, teeth enamel or gland epithelium. Here we show that the transcription factor Meis2 is expressed in the oral region of the first pharyngeal arch (PA1) and later in the tongue primordium. Conditional inactivation of Meis2 in cNCCs resulted in loss of Sonic hedgehog signalling in the oropharyngeal epithelium and impaired patterning of PA1 along the lateral–medial and oral–aboral axis. Failure of molecular specification of PA1, illustrated by altered expression of Hand1/2, Dlx5, Barx1, Gsc and other markers, led to hypoplastic tongue and ectopic ossification of the mandible. Meis2-mutant mice thus display craniofacial defects that are reminiscent of several human syndromes and patients with mutations in the Meis2 gene.
Post-traumatic osteoarthritis development is not modified by postnatal chondrocyte deletion of Ccn2
Authors: Keenan Craig M. , Ramos-Mucci Lorenzo , Kanakis Ioannis , Milner Peter I. , Leask Andrew , Abraham David , Bou-Gharios George , Poulet Blandine 
Published: July 2020

ABSTRACT
CCN2 is a matricellular protein involved in several crucial biological processes. In particular, CCN2 is involved in cartilage development and in osteoarthritis. Ccn2 null mice exhibit a range of skeletal dysmorphisms, highlighting its importance in regulating matrix formation during development; however, its role in adult cartilage remains unclear. The aim of this study was to determine the role of CCN2 in postnatal chondrocytes in models of post-traumatic osteoarthritis (PTOA). Ccn2 deletion was induced in articular chondrocytes of male transgenic mice at 8 weeks of age. PTOA was induced in knees either surgically or non-invasively by repetitive mechanical loading at 10 weeks of age. Knee joints were harvested, scanned with micro-computed tomography and processed for histology. Sections were stained with Toluidine Blue and scored using the Osteoarthritis Research Society International (OARSI) grading system. In the non-invasive model, cartilage lesions were present in the lateral femur, but no significant differences were observed between wild-type (WT) and Ccn2 knockout (KO) mice 6 weeks post-loading. In the surgical model, severe cartilage degeneration was observed in the medial compartments, but no significant differences were observed between WT and Ccn2 KO mice at 2, 4 and 8 weeks post-surgery. We conclude that Ccn2 deletion in chondrocytes does not modify the development of PTOA in mice, suggesting that chondrocyte expression of CCN2 in adults is not a crucial factor in protecting cartilage from the degeneration associated with PTOA.
This article has an associated First Person interview with the first author of the paper.
The Oxford Marston and The Dutch Courtesan
Authors: Butler Martin 
Published: July 2020

This paper situates the play in the context of the ongoing Complete Works of John Marston, under preparation for Oxford University Press, the first such collected critical edition ever to have been created. It discusses the edition’s aims and working practices as well as the new picture of Marston we expect to emerge from it. Scholars now often encounter The Dutch Courtesan in isolation, as Marston’s single best-known and most-read play. This paper approaches the play in the context of Marston’s career and publication history as a whole, in addition to the textual and theatrical relationships which work on the edition is gradually coming to disclose.
Optimization of the <em> apolipoprotein B mRNA editing enzyme catalytic polypeptidelike-3G </em> (<em>APOBEC3G</em>) gene to enhance its expression in <em> Escherichia coli </em>
Authors: Avissa Rizkyana , Widyaningtyas Silvia Tri , Bela Budiman 
Published: July 2020

BACKGROUND Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like-3G (APOBEC3G) can abolish HIV infection by inducing lethal mutations in the HIV genome. The HIV protein virion infectivity factor (Vif) can interact with APOBEC3G protein and cause its degradation. Development of a method that can screen substances inhibiting the APOBEC3G-Vif interaction is necessary for identification of substances that potentially used in anti-HIV drug development. In order to increase expression of recombinant APOBEC3G protein that will be used in APOBEC3G-Vif interaction assay, we developed an optimized APOBEC3G gene for expression in Escherichia coli.
METHODS The gene coding APOBEC3G was codon-optimized in accordance with prokaryotic codon using DNA 2.0 software to avoid bias codons that could inhibit its expression. The APOBEC3G gene was synthesized and sub-cloned into pQE80L plasmid vector. pQE80L containing APOBEC3G was screened by polymerase chain reaction, enzyme restriction, and sequencing to verify its DNA sequence. The recombinant APOBEC3G was expressed in E. coli under isopropyl-β-D-thiogalactoside (IPTG) induction and purified by using nickel-nitrilotriacetic acid (Ni-NTA) resin.
RESULTS The synthetic gene coding APOBEC3G was successfully cloned into the pQE80L vector and could be expressed abundantly in E. coli BL21 in the presence of IPTG.
CONCLUSIONS Recombinant APOBEC3G is robustly expressed in E. coli BL21, and the APOBEC3G protein could be purified by using Ni-NTA. The molecular weight of the recombinant APOBEC3G produced is smaller than the expected value. However, the protein is predicted to be able to interact with Vif because this interaction is determined by a specific domain located on the N-terminal of APOBEC3G.
High-efficiency Er-doped yttrium gallium garnet laser resonantly pumped by a laser diode at 1.47  µm
Authors: You Li , Zhao Yongguang , Lu Dazhi , Liang Fei , Li Lei , Chen Ying , Liu Jian , Wang Jianlei , Yu Haohai , Zhang Huaijin , Wang Jiyang 
Published: July 2020

The spectroscopic and laser properties of an

E
r

3
+

-doped yttrium gallium garnet crystal,

Y

3

G
a

5

O

12

(YGG), are studied. The stimulated emission cross section is

1.4

×

10

−
21

c
m

2

at 1.65 µm. A continuous-wave laser resonantly pumped by a laser diode at 1.47 µm is demonstrated, delivering a maximum output power of 3.34 W. Benefiting from the low phonon energy of the YGG host, the corresponding slope efficiency is as high as

∼

42

%

. To the best of our knowledge, this is the highest slope efficiency from the laser-diode resonantly pumped Er lasers at room temperature in the 1.6 µm spectral range.
Audiovisual Industries and Diversity: Economics and Policies in the Digital Era, Luis A. Albornoz and María Trinidad García Leiva (eds) (2019)
Authors: Muñoz Larroa Argelia 
Published: July 2020

Review of: Audiovisual Industries and Diversity: Economics and Policies in the Digital Era, Luis A. Albornoz and María Trinidad García Leiva (eds) (2019)
New York: Routledge, 210 pp.,
ISBN 978-1-13838-445-3, h/bk, USD 124
SOME ASPECTS OF THE DEFINITION OF THE TERM "TERRORISM"
Authors: Starodubtseva Mariya 
Published: July 2020

The article reveals the lack of accuracy in the definition of the legal term "terrorism" and highlights a number of problems related to this definition. In particular, the author substantiates the need for a clear legal definition of groups of persons targeted by an act of terrorism; it is proved that none of the existing definitions – "civilians", "persons considered innocent" and "non – combatants" - allows us to give an exhaustive definition of the phenomenon. It is noted that the existing definitions of terrorism are incomplete due to insufficient coverage of violent acts of crime. An important unrecorded parameter of the definition of "terrorism" is the factor of publicity of a violent action. In addition, there is need to distinguish between terrorists who are essentially combatants engaged in war and terrorists who are not combatants.
Systems biology graphical notation markup language (SBGNML) version 0.3
Authors: Bergmann Frank T. , Czauderna Tobias , Dogrusoz Ugur , Rougny Adrien , Dräger Andreas , Touré Vasundra , Mazein Alexander , Blinov Michael L. , Luna Augustin 
Published: July 2020

Abstract
This document defines Version 0.3 Markup Language (ML) support for the Systems Biology Graphical Notation (SBGN), a set of three complementary visual languages developed for biochemists, modelers, and computer scientists. SBGN aims at representing networks of biochemical interactions in a standard, unambiguous way to foster efficient and accurate representation, visualization, storage, exchange, and reuse of information on all kinds of biological knowledge, from gene regulation, to metabolism, to cellular signaling. SBGN is defined neutrally to programming languages and software encoding; however, it is oriented primarily towards allowing models to be encoded using XML, the eXtensible Markup Language. The notable changes from the previous version include the addition of attributes for better specify metadata about maps, as well as support for multiple maps, sub-maps, colors, and annotations. These changes enable a more efficient exchange of data to other commonly used systems biology formats (e. g., BioPAX and SBML) and between tools supporting SBGN (e. g., CellDesigner, Newt, Krayon, SBGN-ED, STON, cd2sbgnml, and MINERVA). More details on SBGN and related software are available at http://sbgn.org. With this effort, we hope to increase the adoption of SBGN in bioinformatics tools, ultimately enabling more researchers to visualize biological knowledge in a precise and unambiguous manner.
Comparative Genomic Analyses and a Novel Linkage Map for Cisco (Coregonus artedi) Provide Insights into Chromosomal Evolution and Rediploidization Across Salmonids
Authors: Blumstein Danielle M , Campbell Matthew A , Hale Matthew C , Sutherland Ben J G , McKinney Garrett J , Stott Wendylee , Larson Wesley A 
Published: July 2020

Abstract
Whole-genome duplication (WGD) is hypothesized to be an important evolutionary mechanism that can facilitate adaptation and speciation. Genomes that exist in states of both diploidy and residual tetraploidy are of particular interest, as mechanisms that maintain the ploidy mosaic after WGD may provide important insights into evolutionary processes. The Salmonidae family exhibits residual tetraploidy, and this, combined with the evolutionary diversity formed after an ancestral autotetraploidization event, makes this group a useful study system. In this study, we generate a novel linkage map for cisco (Coregonus artedi), an economically and culturally important fish in North America and a member of the subfamily Coregoninae, which previously lacked a high-density haploid linkage map. We also conduct comparative genomic analyses to refine our understanding of chromosomal fusion/fission history across salmonids. To facilitate this comparative approach, we use the naming strategy of protokaryotype identifiers (PKs) to associate duplicated chromosomes to their putative ancestral state. The female linkage map for cisco contains 20,292 loci, 3,225 of which are likely within residually tetraploid regions. Comparative genomic analyses revealed that patterns of residual tetrasomy are generally conserved across species, although interspecific variation persists. To determine the broad-scale retention of residual tetrasomy across the salmonids, we analyze sequence similarity of currently available genomes and find evidence of residual tetrasomy in seven of the eight chromosomes that have been previously hypothesized to show this pattern. This interspecific variation in extent of rediploidization may have important implications for understanding salmonid evolutionary histories and informing future conservation efforts.
La ciudad como un libro abierto: el flâneur como lector y escritor del espacio híbrido a través de la práctica artística
Authors: Torrecilla Elia 
Published: July 2020

La metáfora de la ciudad como libro abierto despierta la curiosidad de un paseante-lector, ávido por descifrar el enigma urbano. Caminar es un acto poético que ha quedado ejemplificado a través de la figura del flâneur, paseante urbano por excelencia, quien a cada paso toma contacto directo con la ciudad y extrae de ella un relato. A partir de la premisa de que la ciudad es un texto y caminar una forma de lectura y escritura, el presente artículo propone la recuperación de la figura del flâneur moderno para adaptarlo a contextos posteriores, especialmente, aquellos generados por el uso de las tecnologías. En estos contextos, la actualización del flâneur va a permitir abordar un conjunto de prácticas artísticas contemporáneas, donde los creadores asumen su actitud para promover diferentes lecturas de una ciudad palimpsesto. Finalmente, se expone un proyecto personal donde se hace un uso creativo de la tecnología móvil para reivindicar la presencia en las calles como forma de enriquecimiento de la experiencia urbana. De esta manera, cuestiones como la vigilancia y el control que vienen dadas por la tecnología son subvertidas a través del arte, que se sirve del potencial de los medios locativos para proponer una apropiación poética del espacio.
The developmental policy of halal product guarantee in the paradigm of maqāṣid sharī`ah in Indonesia
Authors: Waluyo Agus 
Published: July 2020

The guarantee of halal products that meet the quality, hygiene, health and safety standards has become a primary need for every person to protect religion and soul. This study aims to elaborate government policies related to regulations in supporting the development of halal industry and its barriers to implement halal product guarantee. In addition, this study also tries to reveal halal industrial development strategies. This article is qualitative research using library approach. The research findings show that to guarantee halal product in a systematic and comprehensive way for Indonesian society, the government has issued JPH Law which contains maqāṣid sharī`ah values. Besides, it is found difficulties in the process of obtaining halal certification faced by the producers. This study implies that it still needs rules from the government to support the implementation of JPH Law so that it can encourage the development of halal industry, which finally can establish Indonesia as the epicentre of the world sharia economy.
Derivación urinaria por Cistocentesis Suprapúbica en cirugía por vía vaginal y en otras especialidades Médico Quirúrgicas
Authors: Darnalt Restrepo Enrique , Riaño Rincón Mario , Lucena Quevedo Elkin , Ochoa Alcántara Ricardo 
Published: July 2020

En la Cirugía vaginal se presentan con relativa frecuencia complicaciones del aparato urinario, y por lo tanto el manejo y el cuidado de la vejiga en el post operatorio tienen gran importancia.
Obstetricia en Adolescentes
Authors: Gómez Palacino Jesús Alberto 
Published: July 2020

Puesto que no existe en la literatura médica nacional y es muy escasa la bibliografía del mundo acerca de lo que ocurre en la paciente obstétrica joven, consideramos de interés analizar este capítulo subestimado de la especialidad gineco-obstétrica.
Pedagogical bases of language communicative competence enhancement model of future specialists
Authors: Arymbaeva Kulimkhan , Aldibekova Sh.N. , Abayeva Galiya , Bisenbaeva Zhanat , Kaimova R. , Bisenbaeva Zhanat 
Published: July 2020

This research discusses the issue of language communicative competence (CC) enhancement model. This investigation represents the model of the LCC process with its necessary components applied to the language teaching. This research is of significant value as a contribution to the language teaching policy not only in Kazakhstan but abroad as well. It demonstrates that the CC development process helps to improve the teaching process and make the system work properly. In recent years, in line with the communicative and especially the competence approach in the domestic and foreign science actively developed the problem of enhancement of communicative competence LCC â€˜as a mandatory competency component of profes-sional development of a modern specialistâ€™ in different branches of science such as philosophy, sociology, psychology, peda-gogy, cultural studies, economics and ethics. Such a multifaceted study of the phenomenon of LCC is determined by the dynamics of social life to find the real needs of today's ideological orientation and the necessity of its formation in the learning process. In the present time, a considerable fund is accumulated that allows to explore the topic of the research: issues of implementation of CC enhancement model. The necessity of this research, as it follows from the above, is conditioned by the urgent need to train specialists in LCC in a foreign language in the framework of activities as well as its theoretical and practical underdevelopment.
Keywords: Approach, meta, communicative, competence, modelling.
Analysis of pre-school teachers training in HEI Belarus and Italian multicultural setting
Authors: Spulber Diana , Pavlieva Tatyana 
Published: July 2020

In a globalised world, the school class is the mirror of a changing society. This research aims to identify the readiness of students of the specialty â€˜Pre-school educationâ€™ in Belarus and students of the LM Science of Education in Italy to work in a multicultural environment. Comparative analysis of social land in Italy and Belarus, confrontation of curricula and higher education programmes from the standpoint of the tasks of forming linguistic, communicative, ethnocultural and multicultural competencies, and obtained results from the diagnostics of the culture of interethnic interaction allowed us to identify the possibilities of creative extrapolation of the existing positive experience in the national educational systems. The research materials can be used to improve the theory and practice of multicultural education, and the quality of preparation of pedagogical personnel of pre-school profile for work in a heterogeneous educational environment.
Keywords: Intercultural education, multicultural competence.