bluuebunny/crossref_metadata_2025 huggingface dataset:
L’incertitude à l’égard de l’avenir professionnel : une recherche longitudinale chez des étudiants de doctorat
Authors: Depolo Marco , Fraccaroli Franco , Guglielmi Dina , Mariani Marco , Sarchielli Guido
Published: May 2018

La période des études de doctorat peut être considérée en Italie comme la première étape de la carrière professionnelle universitaire, qui est supposée constituer son issue naturelle. Cette période est caractérisée par une forte incertitude quant à l'avenir, parce que le nombre des postes de chercheur dans les universités est nettement inférieur au nombre des postulants. Les étudiants sont affectés à des équipes de recherche institutionnelles : il est donc possible d'étudier chez eux un véritable processus de socialisation organisationnelle.Cette étude vise à analyser changement et stabilité de l'incertitude professionnelle ressentie par les étudiants doctoraux. Dans le cadre d'une plus vaste recherche, 73 étudiants de la même université italienne (45 % d'hommes, âgés de 28,6 ans en moyenne) ont rempli trois fois un questionnaire : dans la première année du doctorat ; 12 mois après ; et encore 12 mois après. Le questionnaire portait sur la perception de leur avenir professionnel et sur la congruence entre leurs attentes préalables et les conditions de travail auxquelles ils s'étaient confrontés dans les équipes d'affectation. Les résultats ont montré que les étudiants perçoivent leur avenir profession­nel comme incertain : ils déclarent désirer une position académique, mais ce but est jugé par eux plus attractif que réalisable, et plus réalisable que contrôlable. La congruence entre attentes et situation de travail est positivement corrélée à l'avenir professionnel : plus elle est élevée, plus les étudiants déclarent désirer une position universitaire, et plus le contrôle perçu sur l'atteinte de ce but est interne.
Bilan de compétences et transition professionnelle : réduire ou produire de l’incertitude ?
Authors: Gaudron Jean-Philippe , Capdevielle Valérie , Cayasse Nathalie
Published: May 2018

Le but de cette recherche est d'explorer (1) les relations entre les incertitudes qui semblent caractériser les transitions professionnelles des consultants et leurs attentes par rapport à la démarche de bilan et (2) les liaisons entre les fonctions du bilan et les doutes levés ou qui subsistent. L'étude repose sur l'analyse qualitative de quatorze entretiens de bénéficiaires de bilan de compétences menés entre six et douze mois après leur démarche. Les résultats montrent que si le bilan contribue à faire évoluer la situation du sujet, ce n'est pas tant à partir du projet défini au terme du bilan (qui existe), que des interactions entre un conseiller et un bénéficiaire actif, qui amènent ce dernier à lever des doutes sur lui-même, sur ses possibilités et ses compétences et lui font envisager un futur non fait de certitudes, mais d'autres possibles.
El presupuesto general de la nación para 1998
Authors: Editor El
Published: May 2018

No abstract available.Realidad: Revista de Ciencias Sociales y Humanidades No. 60, 1997: 555-557
Las relaciones internacionales y la diplomacia en el conflicto armado
Authors: Martínez Peñate Oscar
Published: May 2018

No abstract available.Realidad: Revista de Ciencias Sociales y Humanidades No. 60, 1997: 587-601
El apoyo ciudadano a la acción extrajudicial de la política en Brasil, El Salvador y Venezuela
Authors: Briceño-León Roberto , Piquet Carneiro Leandro , Cruz José Miguel
Published: May 2018

No abstract available.Realidad: Revista de Ciencias Sociales y Humanidades No. 60, 1997: 603-614
Retazos de Africa. Una mirada a la historia reciente de Ruanda
Authors: Fernández Isabel
Published: May 2018

No abstract available.Realidad: Revista de Ciencias Sociales y Humanidades No. 60, 1997: 615-619
Notas en torno al debate explicación-comprensión
Authors: González Luis Armando
Published: May 2018

No abstract available.Realidad: Revista de Ciencias Sociales y Humanidades No. 60, 1997: 621-650
Planificación urbana y economía en las ciudades centroamericanas
Authors: Lungo Mario
Published: May 2018

No abstract available.Realidad: Revista de Ciencias Sociales y Humanidades No. 60, 1997: 651-665
A Comparative Analysis of News Discourse
Authors: Huang Dengxian
Published: May 2018

In December, 2012, two Tibetan monks involved in the immolation of a Tibetan were detained by Chinese police. The event drew considerable attention from worldwide news agencies. However, the event was presented differently in terms of the different ways of reporting and the different languages employed. This paper examines the two representations of the event that appeared in Chinese and US news media. Processes of text production and linguistic choices are discussed, along with the possible reasons underlying those choices. In this case, the interplay between discourse and ideology is illustrated. Also, it is argued that the comparative analysis of discourse can be considered as an effective way to decode the ideology embedded in a discourse.
Shifting Language Paradigm: An Integration of Five Dimensions of Culture in Teaching English as a Foreign Language in Pakistan
Authors: Zubair Hassan Bin , Qureshi Abrar , Tahir Adnan , Munir Athar
Published: May 2018

This study explores the inseparable entities of language and culture. Mastering the cultural element is crucial in the EFL/ESL language learning process. Furthermore, the study investigates the role of culture in the EFL/ESL curriculum since the 1980s. The paper examines the integration of culture into the ESL/ EFL classrooms in Pakistan. Most Pakistani EFL classrooms continue to simply focus on the grammar-translation approach, where students have to memorize significant and non-significant grammar points and then do dozens of exercises drilling the newly learned grammatical form(s). The foundation for teaching culture language learning include the 5 Cs, the Five Dimensions of Culture, language learning authentic materials, and the Cultural Experiential Learning Cycle. Through experiencing role-playing situations and distinguishing similarities and differences between cultures, students are culturally prepared with appropriate behaviors and responses when they encounter a similar situation in the target culture. The recommendations provided should enable Pakistani educators and administrators to effectively integrate culture into EFL curricula. This Paper explores the incorporation of culture in the context of Pakistani language learning environments. It also investigates strategies and techniques that make the language learning process productive, so that Pakistani educators can incorporate them within their classrooms.
Ervaren complexiteit van sociale professionals die werken met moeilijk bereikbare burgers
Authors: de Jong Jeanet , Jansen Heleen
Published: May 2018

Social work professionals working with ‘hard to reach’ people: the complexity of interagency work

The day to day work of social professionals working with ‘hard to reach’ people, is known to be highly complex. Especially the interdependent relationship with other agencies.

Often problems are not only related to social and welfare themes but also to safety and justice issues. Therefore a wider perspective is asked for. Questions answered in this article are: which elements are being perceived as complex in the relationship with other agencies and how do professionals relate to these elements. Data is used from former research performed within a team working with Roma families. Knowledge, expertise, information sharing and coordination are perceived as complex elements. Good contacts and communication between individual professionals are essential. Understanding each other’s perspective is crucial in achieving a joint effort. Professionals need intensive support in order to keep focused on the values of their work and avoid being led by emotions and issues of the day.
Zelfredzaamheid in detentie
Authors: van Ginneken Esther
Published: May 2018

Self-reliance in detention

In the ‘participation society’ it is expected that citizens actively contribute to solving societal problems, including health care, immigration and security issues. A somewhat similar responsibilisation culture is visible in prisons, where prisoners are held responsible for their own rehabilitation. This article problematizes the way in which prisoners’ agency is promoted in Dutch prisons, considering prisoners’ constrained agency and the normative expectations that are tied to the approach. This critique is advanced through discussion of the promotion/demotion system that has been used in Dutch prisons since 2014. This system, comparable to the Incentives and Earned Privileges system in England and Wales, espouses both ‘hard’ and ‘soft’ behavioural norms. The soft behavioural norms reflect a citizenship ideal that extends beyond compliance with the law. It is argued that these normative expectations tied to agency have a limiting effect on prisoners’ autonomy. This article argues in favour of a shift from the citizenship ideal to an autonomy ideal, which applies the principle of minimum restrictions. Furthermore, access to education, reintegration courses and contact with family should be treated as a right, rather than a privilege, in order to maximise autonomy and minimise the harmful effects of imprisonment.
Grijze gebieden
Authors: Meurs Teun , Visch Amanda
Published: May 2018

Gray Areas – how hybrid professionals perform identity work within the Dutch Police

Public organizations seem to be in a permanent state of transition in an attempt to adapt to the outside world. A recent development is the emergence of hybrid professional roles in fields such as healthcare and primary education. These hybrids are a midway between managerial and professional roles and are expected to collaborate with stakeholders in tackling problems. This article focuses on the challenges of recently appointed hybrid professionals within a Police team in The Netherlands. We focus on their efforts to find a place and position in their team by analyzing some critical incidents in which they clashed with their fellow professionals. In doing so, they perform ‘identity work’ to find out who they are, both for themselves, as for colleagues. We conclude both identity and identity work don’t come natural in a hybrid professional reality and stress the need for facilitation of professional reflection at the organizational level.
Immunology of the eye
Authors: Ratajczak Weronika , Tokarz-Deptuła Beata , Deptuła Wiesław
Published: May 2018

The eye is an organ of sight characterized by unusual immunological properties, resulting from its anatomical structure and physiology, as well as the presence of specific elements that, through the mechanisms of innate and adaptive immunity, provide homeostasis of the eyeball. This article reviews the defensive elements of individual eye structures: conjunctiva, cornea, lacrimal gland, anterior chamber of the eye, uvea, retina and eye-associated lymphoid tissue (EALT), where we distinguish associated lymphoid tissue (CALT) and lacrimal drainage associated lymphoid tissue (LDALT). In addition, the immunity of eyes is conditioned by the difference between the front chamber, anterior chamber – associated immune deviation (ACAID) and also conditioned by the specific barriers of the vascular and retina. These characterized elements, determining the immunity of the eye, are the anatomical, physiological and immunological barrier of the eye, crucial to its immune privilege.
Multidirectional action of resistin in the organism
Authors: Borsuk Anna , Biernat Weronika , Zięba Dorota
Published: May 2018

In recent years obesity is treated as a civilization disorder. It is believed that it is the cause of diseases of many system; moreover, moreover obesity can promote the development of many types of cancers and is a major health hazard for insulin resistance and type 2 diabetes. Currently, the mechanisms underlying the development of obesity are not completely known. Over many years of experiments different factors contributing to the formation of obesity have been recognized. The discovery of resistin as a protein linking obesity to type 2 diabetes marked the beginning of a period of intensive research on this molecule. However, until now its role in the body has been controversial. In rodent resistin is responsible for the development of insulin resistance, but in humans this effect is ambiguous. This protein has strong proinflammatory properties, which can be associated with the development of inflammatory diseases, including atherosclerosis. It is possible that resistin is involved in the regulation of energy homeostasis, mainly by modulating the metabolism of carbohydrates and lipids; also, it acts as anorexigenic compound – it suppresses appetite. Resistin affects the functioning of many body systems, including reproductive and cardiovascular systems. Recent reports
suggest that resistin can play a role in the development of resistance to leptin. The paper
presents the current state of knowledge concerning the biological functions of resistin in
the organism and its potential role in the development of leptin resistance. Leptin resistance
together with hyperinsulinemia and insulin resistance all might lead to disorders of energy
homeostasis and the development of numerous diseases.
Allergic reactions to cow’s milk: pathomechanism, diagnostic and therapeutic strategies, possibilities of food tolerance induction
Authors: Wąsik Magdalena , Nazimek Katarzyna , Bryniarski Krzysztof
Published: May 2018

Cow’s milk is one of the most common causes of allergic reactions in children. Present review summarizes the current knowledge on the pathogenesis, diagnostics and possible therapeutic strategies in this type of allergic immune response. Hypersensitivity reaction to milk components can be mediated by humoral or cell mediated response. There are also mixed types
of reactions, in which both, cells and IgE antibodies are involved. The pathomechanism of
delayed-type hypersensitivity to cow’s milk is still not clear, but possibly it involves Th1 lymphocytes
and macrophages. Clinical manifestations of allergy to cow’s milk may be different,
depending on the underlying mechanism. Routine diagnostic methods are based on specific
IgE-antibodies detection in patients serum, but, if food allergy is suspected, it’s necessary to
also conduct other tests for eventual exclusion of non-IgE-mediated allergy. Immediate and
accurate diagnosis allows to avoid serious gastro-intestinal complications, which may lead
to children developmental disabilities and also weakening of the intestinal epithelium. Other
potential food allergens may penetrate through impaired intestinal barrier to bloodstream,
where they can induce allergic reaction. Recommended therapeutic strategy consists of
elimination of offending food from child diet. Currently, it’s possible to identify the specific
protein responsible for hypersensitivity reaction. It could be especially important if one of
them is bovine serum albumin, because it may be necessary to also exclude beef from diet.
Safety and effectiveness of alternative immunotherapies are still being investigated. The
majority of children acquire tolerance to cow’s milk by the age of 5.
GLOBALIZAÇÃO, INVISIBILIDADE SOCIAL E RECONHECIMENTO: UMA ANÁLISE DA (SO)NEGAÇÃO DE DIREITOS DOS CATADORES DE MATERIAIS RECICLÁVEIS
Authors: Moreira Nelson Camatta , Pinheiro Priscila Tinelli
Published: May 2018

O presente estudo pretende abordar um fenômeno gerado pelas consequências nefastas da globalização que é justamente a formação de um mercado e de profissões informais. Pretende-se, portanto, mostrar as implicações que essa transformação econômica acarreta no aspecto social do país, como o exemplo do aumento do índice de desempregos e a perda de espaço das empresas cuja produção é voltada exclusivamente para o âmbito local. Dessa forma, a partir da análise de um grupo social específico – os catadores de materiais recicláveis – o qual surgiu em um cenário de busca por alternativas ao desemprego, serão apresentados os principais obstáculos enfrentados por indivíduos vítimas do fenômeno da invisibilidade social ao adequado reconhecimento e, para tanto, será utilizada a teoria do reconhecimento em Axel Honneth (2007). Objetiva-se a análise, em face do processo de globalização, do que impede que um grupo social vítima do fenômeno da invisibilidade pública obtenha um reconhecimento pleno perante o Estado e a sociedade da qual faz parte.
Retarded swarming motility in Bacillus subtilis NRS-762 and Pseudomonas aeruginosa PRD-10
Authors: Ng Wenfa
Published: May 2018

Coping with nutritional stress is essential for cell survival, of which many strategies at the cellular level lend support for ensuring the survival of the population at a particular habitat. One postulated mechanism is swarming motility in bacterial cells, where, upon depletion of nutrients at a locale, cells would coordinate their movement, synthesize more flagella, and secrete lubricants for moving rapidly across surfaces in search for food. Known to engage in swarming motility, Bacillus subtilis and Pseudomonas aeruginosa are two common bacterial species with versatile metabolism that use the motility mode to colonize new habitats with more favourable environmental and nutritional conditions. However, experimental observations of bacteria growth on a variety of agar media revealed that B. subtilis NRS-762 (ATCC 8473) and P. aeruginosa PRD-10 (ATCC 15442) exhibited retarded swarming motility upon entry into stationary phase on solid media. Specifically, B. subtilis NRS-762 colonies exhibited round, wrinkled morphologies compared to complex filamented swarming patterns common in strains able to engage in swarming motility. On the other hand, P. aeruginosa PRD-10 colonies were round, mucoid, and expanded outwards from the colony centre without extending filaments from the centre; thereby, indicating retarded swarming motility. Thus, impaired cellular machinery for swarming motility or mutated and deleted genes likely account for observed retarded swarming motility in B. subtilis NRS-762 and P. aeruginosa PRD-10. More importantly, observations of small filaments extending radially from an expanded colony of P. aeruginosa PRD-10 grown on minimal salts medium supplemented with yeast extract highlighted possible loss of function of effector molecules that transmit cellular decision at swarming motility into movement, while sensory mechanisms feeding into the motility mechanism remained intact. More broadly, observations of impaired swarming motility in B. subtilis NRS-762 and P. aeruginosa PRD-10 in two species otherwise endowed with the motility mode highlighted that additional triggers for swarming motility are likely present, and the motility mode may have been evolutionary selected for other functions in addition to foraging for food in times of nutritional stress.
The Influence of advertising media on brand awareness
Authors: Domazet Ivana S. , Đokić Ines , Milovanov Olja
Published: May 2018

In modern business conditions, the company sends its promotional message through various instruments of promotion, and therefore the different media. One of the instruments of promotion is economic propaganda (advertising), which uses a number of media such as television, radio, newspapers, billboards, Internet and others. By using various media, the company affects the consumer awareness of the brand, spreads information about themselves and the brand, educates consumers, creates a brand image and the like. The aim of this study is to investigate the influence of different media of advertising on consumer awareness of the brand, as well as to investigate that influence in the context of socio-demographic characteristics of respondents. The methods used in the work are historical and research (field and online) methods and include a total of 690 respondents from Serbia in the period February-April 2017. For data analysis, we used the independent-samples t-test and the Spearman’s rank correlation coefficient. The results showed that television has the strongest impact on brand awareness. The Internet and billboards follow, while the weakest effect is that of newspapers and radio. Results show that in the context of gender, age, education and income of respondents, there are reasons to analyze the impact of television, radio, newspapers, billboards and the Internet to consumer awareness of the brand in a different manner. The contribution of the thesis is also reflected in the fact that, on the basis of the obtained results, the authors give recommendations, when it comes to perception and brand awareness, on the media that are an adequate promotional instrument for a particular segment of consumers.
TRAF6 interacts with and ubiquitinates PIK3CA to enhance PI3K activation
Authors: Wang Zixi , Liu Yuxiang , Huang Song , Fang Min
Published: May 2018

The PI3K‐AKT signaling pathway regulates cell survival, proliferation, and migration. An abnormal activation of PI3K plays an important role in cancer development. Here, we identify TRAF6 as a potent E3 ubiquitin ligase for the PI3K catalytic subunit PIK3CA (p110α). TRAF6 interacts with PIK3CA and promotes its nonproteolytic polyubiquitination under serum stimulation. TRAF6 ubiquitinates both individual and regulatory subunit‐bound PIK3CA but does not ubiquitinate the regulatory subunit of PI3K. The examination of TRAF6 mRNA expression revealed its upregulation in multiple human malignancies. We demonstrate that overexpression of TRAF6 greatly enhances PI3K activation, leading to an increase in AKT phosphorylation and cell growth. We conclude that TRAF6 is a novel PIK3CA regulator whose deregulated overexpression represents a mechanism for PI3K overactivation in tumors.
Genomewide binding of transcription factor Snail1 in triple‐negative breast cancer cells
Authors: Maturi Varun , Morén Anita , Enroth Stefan , Heldin Carl‐Henrik , Moustakas Aristidis
Published: May 2018

Transcriptional regulation mediated by the zinc finger protein Snail1 controls early embryogenesis. By binding to the epithelial tumor suppressor CDH1 gene, Snail1 initiates the epithelial–mesenchymal transition (EMT). The EMT generates stem‐like cells and promotes invasiveness during cancer progression. Accordingly, Snail1 mRNA and protein is abundantly expressed in triple‐negative breast cancers with enhanced metastatic potential and phenotypic signs of the EMT. Such high endogenous Snail1 protein levels permit quantitative chromatin immunoprecipitation‐sequencing (ChIP‐seq) analysis. Snail1 associated with 185 genes at cis regulatory regions in the Hs578T triple‐negative breast cancer cell model. These genes include morphogenetic regulators and signaling components that control polarized differentiation. Using the CRISPR/Cas9 system in Hs578T cells, a double deletion of 10 bp each was engineered into the first exon and into the second exon–intron junction of Snail1, suppressing Snail1 expression and causing misregulation of several hundred genes. Specific attention to regulators of chromatin organization provides a possible link to new phenotypes uncovered by the Snail1 loss‐of‐function mutation. On the other hand, genetic inactivation of Snail1 was not sufficient to establish a full epithelial transition to these tumor cells. Thus, Snail1 contributes to the malignant phenotype of breast cancer cells via diverse new mechanisms.
Relationship between size‐specific dose estimates and image quality in computed tomography depending on patient size
Authors: Kawashima Hiroki , Ichikawa Katsuhiro , Hanaoka Shinsuke , Matsubara Kosuke , Takata Tadanori
Published: May 2018

This study investigates the relationship between contrast‐to‐noise ratio (CNR) and size‐specific dose estimate (SSDE) in computed tomography (CT) depending on patient size. In addition, the relationship to the auto exposure control (AEC) techniques is examined. A tissue‐equivalent material having human‐liver energy dependence is developed and used to evaluate these relationships. Three exposure dose levels (constant CT dose index, constant SSDE, and with AEC) are tested using four different phantom sizes (diameter: 15, 20, 25 and 30 cm) in two different CT scanners (SOMATOM Definition Flash, Siemens, and LightSpeed VCT, GE). The contrast‐to‐noise ratios (CNRs) are measured using the developed phantom. It is found that the CNR increases with decreasing phantom size at constant SSDE, although the increase ratio is smaller than that of the constant CT dose index. This result indicates that the image characteristics differ even when the patient dose received from the CT examination is equivalent for each patient size. In the case of AEC use, the CNR results of the Siemens scanner exhibit a similar trend to those obtained for constant SSDE, for each phantom size. This suggests that the AEC technique that maintains a constant image quality (CARE Dose 4D) for each patient size corresponds well to the image quality obtained for constant SSDE. These findings facilitate further understanding of the relationship between image quality and exposure CT dose depending on patient size.
Rhodium(I)‐Catalyzed Azide‐Alkyne Cycloaddition (RhAAC) of Internal Alkynylphosphonates with High Regioselectivities under Mild Conditions
Authors: Song Wangze , Zheng Nan , Li Ming , Ullah Karim , Zheng Yubin
Published: May 2018

A regioselective method to access fully substituted 1,2,3‐triazolyl‐4‐phosphonates from the internal alkynylphosphonates by rhodium(I)‐catalyzed azide‐alkyne cycloaddition (RhAAC) under mild conditions is reported. This approach is water and air compatible and has a broad substrate scope, good functional group tolerance, high yields and excellent regioselectivities. Fully substituted 1,2,3‐triazolyl‐4‐phosphonates are directly prepared from the internal alkynylphosphonates by RhAAC with high 1,4‐regioselectivities. The gram‐scale preparation, application to carbohydrate synthesis and the solid‐phase synthesis of triazolyl‐4‐phosphonates are highlights of this method.

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Identification of an Asexual Reproduction Inducer of Phytopathogenic and Toxigenic Fusarium
Authors: Qi Jianhua , Cheng Lihong , Sun Yujuan , Hirata Yushi , Ushida Naoki , Ma Zhonghua , Osada Hiroyuki , Nishikawa Toshio , Xiang Lan
Published: May 2018

Asexual and sexual reproduction are the most important biological events in the life cycle of phytopathogenic and toxigenic Fusarium and are responsible for disease epidemics. However, the signaling molecules which induce the asexual reproduction of Fusarium are unknown. Herein we describe the structure elucidation, including the absolute configuration, of Fusarium asexual reproduction inducer (FARI), a new sesquiterpene derivative, by spectroscopic analysis, total synthesis, and conidium‐inducing assays of synthetic isomers. We have also uncovered the universality of FARI among Fusarium species. Moreover, a mechanism‐of‐action study suggested that the Gpmk1 and LaeA signaling pathways are required for conidium formation induced by FARI; conversely, the Mgv1 of mitogen‐activated protein kinase is not involved in conidium formation. FARI exhibited conidium‐inducing activity at an extremely low dose and high stereoselectivity, which may suggest the presence of a stereospecific target.
Vinyl Sulfonate Esters: Efficient Chain Transfer Agents for the 3D Printing of Tough Photopolymers without Retardation
Authors: Seidler Konstanze , Griesser Markus , Kury Markus , Harikrishna Reghunathan , Dorfinger Peter , Koch Thomas , Svirkova Anastasiya , Marchetti‐Deschmann Martina , Stampfl Juergen , Moszner Norbert , Gorsche Christian , Liska Robert
Published: May 2018

The formation of networks through light‐initiated radical polymerization allows little freedom for tailored network design. The resulting inhomogeneous network architectures and brittle material behavior of such glassy‐type networks limit the commercial application of photopolymers in 3D printing, biomedicine, and microelectronics. An ester‐activated vinyl sulfonate ester (EVS) is presented for the rapid formation of tailored methacrylate‐based networks. The chain transfer step induced by EVS reduces the kinetic chain length of the photopolymer, thus shifting the gel point to higher conversion, which results in reduced shrinkage stress and higher overall conversion. The resulting, more homogeneous network is responsible for the high toughness of the material. The unique property of EVS to promote nearly retardation‐free polymerization can be attributed to the fact that after the transfer step no polymerizable double bond is formed, as is usually seen in classical chain transfer agents. Laser flash photolysis, theoretical calculations, and photoreactor studies were used to elucidate the fast chain transfer reaction and exceptional regulating ability of EVS. Final photopolymer networks exhibit improved mechanical performance making EVS an outstanding candidate for the 3D printing of tough photopolymers.
Implementation of Fully Integrated Continuous Antibody Processing: Effects on Productivity and COGm
Authors: Arnold Lindsay , Lee Kenneth , Rucker‐Pezzini Joanna , Lee Jeong H.
Published: May 2018

The changing landscape of the biopharmaceutical market is driving a paradigm shift toward continuous manufacturing. To date, integrated continuous bioprocessing has not been realized as enabling technologies are nascent. In this work, a fully integrated continuous process is successfully demonstrated from pilot scale bioreactor to drug substance. Comparable product quality is observed between the continuous process and a 500 L fed‐batch conventional process. The continuous process generated material at a rate of 1 kg of purified mAb every 4 days, achieving a 4.6‐fold increase in productivity compared to the fed‐batch process A plant throughput analysis using BioSolve software shows that a fed‐batch facility with 4 × 12 500 L stainless steel bioreactors and purification train of the corresponding scale can be replaced by a continuous facility consisting of 5 × 2000 L single use bioreactors and smaller purification train, with a cost reduction of 15%.
A rapid and sensitive LC–MS/MS method for analysis of iguratimod in human plasma: Application to a pharmacokinetic study in Chinese healthy volunteers
Authors: Xia Ying , Zhao Shunbo , Gong Meng , Ding Li
Published: May 2018

A rapid, sensitive and reproducible LC–MS/MS method was developed and validated to determine iguratimod in human plasma. Sample preparation was achieved by protein precipitation with acetonitrile. Chromatographic separation was operated on an Ultimate® XB‐C18 column (2.1 × 50 mm, 3.5 μm, Welch) with a flow rate of 0.400 mL/min, using a gradient elution with acetonitrile and water which contained 2 mm ammonium acetate and 0.1% formic acid as the mobile phase. The detection was performed on a Triple Quad™ 5500 mass spectrometer coupled with an electrospray ionization interface under positive‐ion multiple reaction monitoring mode with the transition ion pairs of m/z 375.2 → 347.1 for iguratimod and m/z 244.3 → 185.0 for agomelatine (the internal standard), respectively. The method was linear over the range of 5.00–1500 ng/mL with correlation coefficients ≥0.9978. The accuracy and precision of intra‐ and inter‐day, dilution accuracy, recovery and stability of the method were all within the acceptable limits and no matrix effect or carryover was observed. As a result, the main pharmacokinetic parameters of iguratimod were as follows: Cmax, 1074 ± 373 ng/mL; AUC0–72, 13591 ± 4557 ng h/mL; AUC0–∞, 13,712 ± 4613 ng h/mL; Tmax, 3.29 ± 1.23 h; and t1/2, 8.89 ± 1.23 h.
Synthesis and Biological Evaluation of Homogeneous Thiol‐Linked NHC*‐Au‐Albumin and ‐Trastuzumab Bioconjugates
Authors: Matos Maria J. , Labão‐Almeida Carlos , Sayers Claire , Dada Oyinlola , Tacke Matthias , Bernardes Gonçalo J. L.
Published: May 2018

Targeted delivery of potent cytotoxic drugs to cancer cells minimizes systemic toxicity and several side effects. NHC*−Au−Cl has already been proven to be a potent anticancer agent. In this study, we explore a strategy based on chemoselective cysteine conjugation of NHC*−Au−Cl to albumin and trastuzumab (Thiomab LC‐V205C) to potentiate drug‐ligand ratio, pharmacokinetics, as well as drug efficacy and safety. This strategy is a step forward towards the use of gold‐based anticancer agents as targeted therapies.
First Total Synthesis and Structural Confirmation of C13‐Butylrubber Oligomers
Authors: Minicone Fabrizio , Attrill Robin , Hodgson Michael , Wheelhouse Katherine , Dobbs Adrian
Published: May 2018

The first total synthesis of an important C13 butyl rubber oligomer is reported. The structure of the oligomer, which is an important and potentially toxic extractable and leachable component of elastomeric closures, is confirmed by synthesis for the first time. The method described is scalable, making large quantities of the oligomer available for the first time for AMES toxicity studies. The challenging synthesis commences with isophorone and the key steps of the synthesis involve the development of highly novel dithoacetal chemistry, cuprate addition and Tebbe olefination.
Physicochemical characterization of natural dolomite for efficient removal of lead and cadmium in aqueous systems
Authors: Sdiri Ali
Published: May 2018

Physicochemical characterization of naturally abundant carbonates has been undertaken to evaluate their potentialities in the removal of lead and cadmium ions in aqueous systems. Powdered dolomite samples, collected from the Jebel Rehach location, southern Tunisia, were used in their natural form for the removal of both cadmium and lead in aqueous conditions. The removal experiments were carried out in batch by mixing known amount of dolomite powder with a metal solution (lead or cadmium). The mixture was shaken at 200 rpm under the experimental conditions of pH 6, temperature (25°C), dolomite concentration 3 g/L, and cadmium 10 mg/L and lead 100 mg/L solutions. Shaking time was 60 min. Our results showed that the studied dolomite samples were mainly composed of calcium and magnesium oxides; other impurities were also detected. Adsorption data showed that dolomitic samples of the Triassic Rehach formation (southern Tunisia) removed substantial amounts of lead and cadmium ions in aqueous systems. It was found that lead removal efficiency reached 24.80 and 33.25 mg/g, which is much higher than that of cadmium (1.31–1.77 mg/g). It was also observed that more than 95% of the total adsorptive capacity was achieved after 30 min of agitation, but 60 min was used to ensure equilibration time. These results suggested that the Triassic Rehach dolomite, Tunisia, can be effectively used for capturing lead and cadmium ions in aqueous conditions. © 2018 American Institute of Chemical Engineers Environ Prog, 37: 1901–1907, 2018
Zero valent cobalt impregnated silica nanoparticles for the sanitation of contaminated water
Authors: Shukla Nivedita , Gupta Vatsana , Pal Deepak Kumar , Rawat Ashok Singh , Saxena Amit , Shrivastava Sarita , Rai Pramod Kumar
Published: May 2018

Cobalt impregnated silica nanoparticles (Co–SiO2) were synthesized via one pot method involving supercritical drying followed by in‐situ reduction. The prepared nanoparticles were characterized by nitrogen‐Brunauer Emmett Teller (N2‐BET) isotherm studies, X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta particle size analyzer and vibrating sample magnetometer (VSM) techniques. The Co–SiO2 nanoparticles were evaluated for adsorptive removal of methylene blue (MB), trinitrotoluene (TNT), and mercury ions [Hg (II)]. The equilibrium adsorption data were analyzed using Langmuir, Freundlich and Dubinin–Radushkevich (D–R) isotherm models. Adsorption of MB and Hg(II) were best fitted by Langmuir isotherm model depicting their homogenous monolayer adsorption with maximum adsorption capacity of 250 and 40.24 mg/g, respectively, while TNT adsorption was best fitted by Freundlich isotherm model indicating a heterogeneous adsorption with 20.49 mg/g adsorption capacity. The mean adsorption energy calculated through D–R model indicated physisorption of all the three contaminants by the adsorbent. Thermodynamic studies showed that the adsorption of these contaminants was spontaneous and endothermic process with increased randomness at the solid/solution interface. The magnetic Co/SiO2 nanoparticles were easily separated after adsorption process with the help of a magnet and showed a reusability upto three cycles without much loss in adsorption efficiency. © 2018 American Institute of Chemical Engineers Environ Prog, 38: S42–S53, 2019
Designing and operation of pilot scale continuous stirred tank reactor for continuous production of bio‐methane from toxic waste
Authors: Singhal Shailey , Agarwal Shilpi , Singhal Naveen , Sharma Rajan , Sharma Rohit
Published: May 2018

Increased use of biofuels from non‐renewable resources is required for sustainable development of the society. Biogas being almost pure methane, occupies importance to be used in place of compressed natural gas as transportation fuel in future. Lignocellulosic biomass (agricultural and forestry residues) are inexpensive and abundantly available source of energy. Pilot scale continuous stirred tank reactor was designed for jatropha de‐oiled cake (JDOC) with a total capacity of 40 m3. JDOC was digested with cow dung (3:1) in pilot scale reactor for continuous production of biogas for 120 days at 35°C. Around 20 m3 biogas was produced per day as a regular operation in only 5 days. © 2018 American Institute of Chemical Engineers Environ Prog, 38: 198–200, 2019
Fixed bed column adsorption of Cr(VI) from aqueous solution using nanosorbents derived from magnetite impregnated Phaseolus vulgaris husk
Authors: Srivastava Shalini , Agrawal S. B. , Mondal M. K.
Published: May 2018

Phaseolus vulgaris husk impregnated with magnetite (Fe3O4) was successfully synthesized by co‐precipitation method as nanosorbents for characterization study and utilized for Cr(VI) biosorption from aqueous solution. Scanning electron microscopy, transmission electron microscopy, Fourier Transform infrared spectroscopy, and BET techniques were applied for nanosorbent characterization. In fixed bed column condition, influence of important process parameters like pH, influent concentration, flow rate, and bed height on adsorption of Cr(VI) by magnetite impregnated P. vulgaris husk were investigated. Maximum adsorption capacity at pH 1.16, influent Cr(VI) concentration 100 mg/L, flow rate 5 mL/min, and bed depth of 3.2 cm was calculated to be 53.28 mg/g. The breakthrough time and column exhaustion time showed inverse relation with pH, influent concentration, flow rate, and direct with bed depth. Bohart–Adams, Thomas, and Yoon–Nelson models were used to predict column performance. Compared to Bohart–Adams, Thomas, and Yoon–Nelson models fitted well to experimental data. © 2018 American Institute of Chemical Engineers Environ Prog, 38: S68–S76, 2019
Phosphate removal from aqueous solutions by nano‐alumina for the effective remediation of eutrophication
Authors: Yadav Deepak , Kumar Pradeep , Kapur Meghna , Mondal Monoj Kumar
Published: May 2018

Excessive phosphate effluent discharged in the surface water source rush to eutrophication. Consecutively this disturbs the water quality and aquatic ecosystem, due to the depletion of dissolved oxygen. Reduced oxygen level in water bodies affects aquatic life and decreases biodiversity. The present investigation emphasized the phosphate adsorption over nano‐alumina. Surface characteristics of the adsorbents, BET, FTIR, XRD, TEM, and SEM were analyzed to reveal the phosphate adsorption mechanisms. The adsorption isotherms, kinetics, pH effect were observed in batch experiments. The pHpzc value of nano‐alumina adsorbent was found as 8.1. The maximum phosphate adsorption was found to be 98.75% at contact time of 90 min and pH 6. Different models, e.g., Langmuir, Freundlich, Temkin, and Dubinin‐Radushkevich were used for isotherm study. The kinetic data were tested by pseudo‐first order and second order models. An attempt was made to regenerate the spent adsorbent for reuse in the adsorption process. Low cost and high capability of nano‐alumina make it feasible to utilize as cost‐effective phosphate remediation from wastewater. © 2018 American Institute of Chemical Engineers Environ Prog, 38: S77–S85, 2019
Effect of variation in the C/[N+P] ratio on anaerobic digestion
Authors: Gil Aida , Siles Jose A. , Serrano Antonio , Chica Arturo F. , Martín M. Angeles
Published: May 2018

The importance of the balance between the nutrients in the anaerobic digestion process was assessed at laboratory scale. A soluble synthetic solution was used as substrate. The variable used to monitor the proportion of nutrients in the substrate was the [C]/[N + P] ratio expressed as equivalents of each element. A blank assay with a constant ratio of 53 and three experiments in which this variable was modified in the range 53–1 were performed. An increase in the concentration of nitrogen and phosphorus both separately and in combination was observed. The most relevant results show a loss of N in the biogas in the form of NH3 for concentrations of around 400 mg N soluble/L in the liquid phase of the reaction, and a loss of soluble phosphorus in the form of calcium phosphate due to precipitation at concentrations above 250 mg P soluble/L, regardless of the experimental procedure. No significant effects were observed in the production of biogas for a ratio in the range 53–40, while biogas production decreased by 8% for a ratio of 20 when both N and P increased in the best of cases and by up to 46% when only N increased. © 2018 American Institute of Chemical Engineers Environ Prog, 38: 228–236, 2019
The fabrication of 3D porous PDMS sponge for Oil and organic solvent absorption
Authors: Guo Jiahong , Wang Jikui , Wang Wenqi , Bai Zhiwei , Zhang Zhibing , Zhang Yajuan , Zhang Shiping
Published: May 2018

The separation of oil–water mixtures is increasingly desired due to the environmental protection and industrial production. However, the low‐oil capacity and complicated procedures in current systems remain challenging issues. Herein, porous polydimethysiloxane (PDMS) sponges are fabricated by polymerization of the prepolymer and a curing agent with the combination of NaHCO3 foaming and CO2 template method, which is novel, simple, and economical. EDS and XPS measurements prove the successful fabrication of PDMS sponges. This as‐prepared PDMS sponges show high absorption capacity (694–2513%), hydrophobicity/oleophilicity property (water contact angle and oil contact angle are 139° and 0°), and excellent thermal property. The PDMS sponges can selectively absorb a large amount of floating oils on the water surface and heavy oils under the water, and show little change of its capacities after 20 absorbing/reabsorbing cycles. © 2018 American Institute of Chemical Engineers Environ Prog, 38: S86–S92, 2019
The effect of alternate wetting and severe drying irrigation on grain yield and water use efficiency of Indica‐japonica hybrid rice (Oryza sativa L.)
Authors: Chu Guang , Chen Tingting , Chen Song , Xu Chunmei , Wang Dangying , Zhang Xiufu
Published: May 2018

Identification of a rice cultivar with high yield potential has been heavily sought by researchers in China, and pursuant to this goal, several indica‐japonica hybrid rice (IJHR) cultivars have been studied for over a decade. However, in addition to high yield, it is important that the cultivar also exhibit good water use efficiency (WUE). This study compared the yield performance and WUE of the IJHR cultivars under alternate wetting and severe drying (AWSD) irrigation regimen to the japonica inbred rice (JIR) cultivars. Field experiments were conducted on two representative IJHR cultivars (Chunyou927 and Yongyou538) and two representative JIR cultivars (Xiushui09 and Zhejing99) in 2015 and 2016 with two different irrigation methods: continuous flooding (CF) and AWSD. Irrigation water was 275–349 mm in the AWSD irrigation regimen, which was 49.8%–56.2% of that (552–620 mm) applied to the CF irrigation regimen. Compared to CF, the AWSD irrigation method significantly decreased grain yield in both IJHR and JIR cultivars, with a more significant reduction in JIR cultivars, and WUE was improved in both the IJHR and JIR cultivars, especially in the IJHR cultivars. Compared to the JIR cultivars, the IJHR cultivars were found to have improved agronomic and physiological performances under the AWSD irrigation regimen, such as a larger sink size, higher percentage of productive tillers, higher matter production ability during reproductive and ripening periods, larger root biomass, deeper root distribution and greater nonstructural carbohydrate (NSC) accumulation in the stem at heading, larger NSC remobilization from the stem, and higher root oxidation activity and leaf photosynthetic rates during ripening period. Improved agronomic and physiological traits contributed to an increase in WUE with less yield loss for IJHR cultivars under the AWSD irrigation regimen.
Excessive Plasmin Compromises Hepatic Sinusoidal Vascular Integrity After Acetaminophen Overdose
Authors: Gao Siqi , Silasi‐Mansat Robert , Behar Amanda R. , Lupu Florea , Griffin Courtney T.
Published: May 2018

The serine protease plasmin degrades extracellular matrix (ECM) components both directly and indirectly through activation of matrix metalloproteinases. Excessive plasmin activity and subsequent ECM degradation cause hepatic sinusoidal fragility and hemorrhage in developing embryos. We report here that excessive plasmin activity in a murine acetaminophen (APAP) overdose model likewise compromises hepatic sinusoidal vascular integrity in adult animals. We found that hepatic plasmin activity is up‐regulated significantly at 6 hours after APAP overdose. This plasmin up‐regulation precedes both degradation of the ECM component fibronectin around liver vasculature and bleeding from centrilobular sinusoids. Importantly, administration of the pharmacological plasmin inhibitor tranexamic acid or genetic reduction of plasminogen, the circulating zymogen of plasmin, ameliorates APAP‐induced hepatic fibronectin degradation and sinusoidal bleeding. Conclusion: These studies demonstrate that reduction of plasmin stabilizes hepatic sinusoidal vascular integrity after APAP overdose. (Hepatology 2018; 00:1‐13).
CD2‐Associated Protein Contributes to Hepatitis C, Virus Propagation and Steatosis by Disrupting Insulin Signaling
Authors: Zhang Huixia , Zhang Chao , Tang Hong , Gao Shanshan , Sun Fang , Yang Yuan , Zhou Weiping , Hu Yu , Ke Changshu , Wu Yu , Ding Zeyang , Guo Lin , Pei Rongjuan , Chen Xinwen , Sy Man‐Sun , Zhang Bixiang , Li Chaoyang
Published: May 2018

Chronic hepatitis C virus (HCV) infection can result in steatosis, a condition displaying aberrant accumulation of neutral lipid vesicles, the component of lipid droplets (LDs), which are essential for HCV assembly. However, the interplay between HCV infection and steatosis remains unclear. Here, we show that HCV‐infected cells have higher levels of CD2‐associated protein (CD2AP), which plays two distinct, yet tightly linked, roles in HCV pathogenesis: Elevated CD2AP binds to nonstructural protein 5A (NS5A) and participates in the transport of NS5A to LDs to facilitate viral assembly; Up‐regulated CD2AP also interacts with casitas B‐lineage lymphoma (b) (Cbl/Cbl‐b) E3 ligases to degrade insulin receptor substrate 1 (IRS1), which, in turn, disrupts insulin signaling and increases LD accumulation through the IRS1/protein kinase B (Akt)/adenosine monophosphate‐activated protein kinase (AMPK)/hormone‐sensitive lipase (HSL) signaling axis to accommodate viral assembly. In the HCV‐infected mouse model, CD2AP expression is up‐regulated during the chronic infection stage and this up‐regulation correlates well with liver steatosis. Importantly, CD2AP up‐regulation was also detected in HCV‐infected human liver biopsies showing steatosis compared to non‐HCV‐infected controls. Conclusion: CD2AP is indicated as a protein up‐regulated by HCV infection, which, in turn, stimulates HCV propagation and steatosis by disrupting insulin signaling; targeting CD2AP may offer an opportunity for alleviating HCV infection and its associated liver pathology. (Hepatology 2018;XX:XXX‐XXX.)