bluuebunny/crossref_metadata_2025 huggingface dataset:
Boundary conditions for the Middle Miocene Climate Transition (MMCT v1.0)
Authors: Frigola Amanda , Prange Matthias , Schulz Michael
Published: April 2018

Abstract. The Middle Miocene Climate Transition was characterized by major Antarctic
ice sheet expansion and global cooling during the interval
∼ 15–13 Ma. Here we present two sets of boundary conditions for
global general circulation models characterizing the periods before (Middle
Miocene Climatic Optimum; MMCO) and after (Middle Miocene Glaciation; MMG)
the transition. These boundary conditions include Middle Miocene global
topography, bathymetry, and vegetation. Additionally, Antarctic ice volume
and geometry, sea level, and atmospheric CO2 concentration estimates for
the MMCO and the MMG are reviewed. The MMCO and MMG boundary conditions have
been successfully applied to the Community Climate System Model version 3
(CCSM3) to provide evidence of their suitability for global climate modeling.
The boundary-condition files are available for use as input in a wide variety
of global climate models and constitute a valuable tool for modeling studies
with a focus on the Middle Miocene.
Characterizing the Potential for Drought Action from Combined Hydrological
and Societal Perspectives
Authors: Towler Erin , Lazrus Heather , PaiMazumder Debasish
Published: April 2018

Abstract. Drought is a function of both natural and human influences, but fully characterizing the interactions between human and natural influences on drought remains challenging. To better characterize parts of the drought feedback loop, this study combines hydrological and societal perspectives to characterize and quantify the potential for drought action. For the hydrological perspective, we examine historical groundwater data, from which we determine the decadal likelihoods of exceeding hydrologic thresholds relevant to different water uses. Stakeholder interviews yield data about how people rate the importance of water for different water uses. We combine these to quantify the Potential Drought Action Index (PDAI). The PDAI is demonstrated for a study site in south-central Oklahoma, where water availability is highly influenced by drought and management of water resources is contested by local stakeholders. For the hydrological perspective, we find that the historical decadal likelihood of exceedance for a moderate threshold associated with municipal supply has ranged widely: from 23 % to 75 %, which corresponds well with natural drought variability in the region. For the societal perspective, stakeholder interviews reveal that people value water differently for various uses. Combining this information into the PDAI illustrates that potential drought action increases as the hydrologic threshold is exceeded more often; this occurs as conditions get drier and when water use thresholds are more moderate. The PDAI also shows that for water uses where stakeholders have diverse views of importance, the PDAI will be diverse as well, and this is exacerbated under drier conditions. The variability in stakeholder views of importance is partially explained by stakeholders' cultural worldviews, pointing to some implications for managing water when drought risks threaten. We discuss how the results can be used to reduce potential disagreement among stakeholders and promote sustainable water management, which is particularly important for planning under increasing drought.
Restoraktiv Justice Policy in the Investigation of Children as Trafficking Actor
Authors: Hapsari Ifahda Pratama
Published: April 2018

A forced effort by the investigator of the child of investigation because the investigator can not rule out a perpetrator. Nevertheless, the maximum effort of handling child offenders in non-litigation cases is preferred by looking at the nature of the child and Non penal sanction is more appropriate for the child of the offender. Furthermore, the action that can be carried out by the investigator on the child of the Trafficking Trafficking in Law Number 11 Year 2012, to substitute for restitution restitution, and the return to the parent / guardian is a matter that is deemed appropriate, since the investigator has no authority to override the case, even in conduct investigations with more emphasis on prioritizing restorative justice rather than formal legalistic considerations.
Hairy Apes and Quare Fellows: The Legacy of Eugene O'Neill in the Work of Brendan Behan
Authors: McMahon Deirdre
Published: April 2018

Brendan Behan (1923–64) was part of a Dublin theater community that grew up with the plays of Eugene O'Neill on its doorstep, and the impact was significant. As John P. Harrington notes, when the Dublin Drama League produced O'Neill's Emperor Jones in 1927, Denis Johnston described it as “the first true invasion of the modern into the national theatre [of Ireland].” By immersing himself into Dublin's modernist theater culture during his early years, Behan fed his interest in the avant-garde, which resulted in The Quare Fellow, a play that has some remarkable thematic and formal similarities to O'Neill's The Hairy Ape. Each writer emerged from fringe theater, and each turned to European expressionism to challenge issues around social justice and equality. This article surveys O'Neill's significance in the Dublin of Behan's youth, considers the sociopolitical affinities between the writers, and analyzes the theatrical aesthetics of each in their respective plays The Hairy Ape and The Quare Fellow.
Projeto ótimo de Pilares em Concreto de Alta Resistência Segundo ABNT NBR 6118:2014
Authors: Alves Elcio Cassimiro , Souza Paula Mayer dos Santos
Published: April 2018

O dimensionamento de pilares de concreto armado é, em geral, baseado na experiência do projetista, que analisa as cargas a que estão submetidos e define uma seção que seja capaz de resistir aos esforços solicitantes e de atender às especificações da normalização vigente. Este artigo objetiva apresentar a formulação e os critérios definidos pela ABNT NBR 6118:2014 para o dimensionamento de pilares de concreto armado, retangulares e circulares, com resistências acima de 50MPa e definir a geometria otimizada, a mais econômica, entre as inúmeras capazes de resistir ao carregamento existente. A otimização foi realizada no software Matlab, pelo método dos pontos interiores. Serão analisados exemplos numéricos de modo a verificar a viabilidade da utilização de pilares com concreto de alta resistência na obtenção da seção mais econômica. Dessa forma, percebeu-se que pilares com essa resistência são indicados quando há imposição de dimensões ou necessidade de redução de seções.
Research on the Influencing Factors of High School English Teacher Professional Learning Community Evaluation in Changchun, China
Authors: Li Yang , Tu Chia-Ching
Published: April 2018

This research shows the development and influencing factors of high school English teachers’ evaluation of professional learning community in Changchun, China. Followed Olivier and Hipp & Huffma’s research, the teacher professional learning community evaluation questionnaire was developed by the researchers. 422 English teachers in Changchun were invited to participate in the online survey. This study found that the organization characteristics of professional learning communities in this city shared similar characteristics with Western countries at some degree. English perceptions of including the “shared personal practice” and “collective learning and application” achieves the average level in this research. Compared to the western professional learning communities, the Chinese professional learning communities in this study lack of the democratic leadership and shared value and vision attributions. According to the analysis, we find that the Confucian cultural context, teacher’ career development stages, the pressures of national college entrance examination and the systematic teaching training have a significant impact on the evaluation of teacher professional learning communities. Aiming at to build a learning organisation rather than a bureaucratic administration, we suggest that the “shared value and vison” and “shared and supportive leadership” needs more reform in the current professional learning communities. Namely, traditional Soviet model of school-based professional learning communities need to reform toward a learning organisation emphasizing the teaching and learning.
A Genre-Based Approach to Writing Instruction in EFL Classroom Contexts
Authors: Nagao Akiko
Published: April 2018

This study explored how 14 foreign-language writers at a university in Japan changed their genre awareness of discussion genre texts (particularly argumentative essays) during a 15-week systemic functional linguistics course consisting of text-based writing lessons assigned as part of a teaching and learning cycle. To obtain in-depth quantitative and qualitative insights into changes in the students’ awareness of genre and writing skills, pre- and post-surveys and self-reflection written texts were administered and analyzed. Twelve previously proposed criteria (covering generic structure, lexicogrammar, and multidimensional analyses of attitudes and performance) were used to analyze the self-reflection texts. The preliminary results showed that the students’ understanding of generic structure and lexicogrammar improved, especially their comprehension of the second and third paragraphs of the target genre text. The preliminary results of the correlation analysis illustrated that the increased understanding of lexicogrammatical features, such as textual meaning, interpersonal meaning, and experiential meaning, was related to their self-efficacy and confidence in their writing skills. The preliminary analysis results indicated that that applying a teaching and learning cycle and a genre-based approach to writing instruction has the potential to enhance EFL students’ awareness of generic structure and interpersonal meaning in writing argumentative essays.
Critical Metaphor Analysis of Political Discourse in Nigeria
Authors: Agbo Isaiah I. , Kadiri Goodluck C. , Ijem Blessing Ugo
Published: April 2018

Metaphor is an important figure of speech copiously deployed in political discourse. In this study, we adopted the framework of Charteris-Black’s (2004) Critical Metaphor Analysis (CMA) which derives from Critical Discourse Analysis (CDA).This framework is interested in exploring the implicit intentions of language users, the ideological configurations and the hidden power relations within socio-political and cultural contexts. It captures the ideological and conceptual nature of metaphor, and transmits truth alive into the hearts of the people by passion. The thrust of this study is the identification, analysis and interpretation of the ideological and conceptual metaphors in the speeches we studied that create a particular linguistic style, conceptualize the speakers’ experiences and transmit their ideologies for rhetoric and argumentation purposes. The corpus of this study is limited to the political speeches of Brigadier Sani Abacha in 1984 and 1993, General Ibrahim Babangida in 1985 and 1993, M.K.O. Abiola in 1993 and 1994, and Goodluck Ebele Jonathan in 2013. The study reveals that the speakers use metaphors as tools to enact power and wield influence on their audience. There is further the use of metaphors for the purpose of argumentation thereby promoting self-ideologies and power asymmetric. Furthermore, the study shows that the speakers in the speeches we analysed use metaphors as a strategy to identify with the people so as to create a bond between them. Finally, our speakers use metaphors to manipulate their audience both mentally and conceptually, polarize between them and the conceived enemies, and dominate their audience; and conceal and conceptualize experience in order to reframe realities to suit their interests.
Public Private Partnerships and Collaboration in the Health Sector in the Kingdom of Saudi Arabia: A Qualitative Study
Authors: Almalki Amal , Al-Hanawi Mohammed
Published: April 2018

A public-private partnership (PPP) is defined as a collaboration between the public and private sectors in the financing, delivery and development of public goods and services. This phenomenon has been adopted globally by many as a new economic paradigm. This study identifies challenges and other hindrances in promoting PPPs, identifies the concrete contribution of PPP initiatives in improving healthcare service delivery and determines the level of participation of the private sector in healthcare delivery systems under PPP initiatives in the Kingdom of Saudi Arabia. Semi-structured interviews were conducted with 13 participants, including 4 government hospital directors, 5 private hospital directors and 4 health personnel. Participants were interviewed face to face, and the interviews were audio-recorded. The participants were purposefully selected based on their knowledge and familiarity with the implementation of PPP schemes. The evidence showed that the most important benefits of adopting a PPP are the quality of service, the speed at which low-cost healthcare service delivery is made accessible and the diversification of risks between the two sectors so that neither the private sector nor the public sector bears the entire risk alone. The results also revealed that PPPs will lead to increased efficiency and accuracy with respect to the design and implementation of infrastructural projects as well as the financing, execution, maintenance and development of the healthcare sector—the implementation of which makes high-quality services available to end users. Risk sharing is of great importance for the healthcare sector in that it helps hospitals to avoid closure and failure, distributes financial flows in an ideal way, and reduces the pressure on hospitals to work in a safe investment environment. This aim can be achieved through increasing the partnerships between public and private sectors.
Directors’ Remuneration and Firm’s Performance: A Study on Malaysian Listed Firm under Consumer Product Industry
Authors: Mohd Razali Mohd Waliuddin , Yee Ng Sue , Hwang Josephine Yau Tan , Tak Akmal Hisham Bin , Kadri Norlina
Published: April 2018

Remuneration is broadly used as an incentive that affects decisions made and strategies planned by directors which cause great impact on firm performance and profitability. This study aims to investigate the directors’ remuneration of the consumer products sector focusing particularly on Malaysian listed companies under Consumer Product Industry. These firm’s performances are measured by return on assets (ROA) and return on equities (ROE). This study consists a sample of 40 Malaysian listed companies for the period of 2012 to 2014. After controlling for board size, CEO duality, firm size, firm age, and leverage; the regression results show director remuneration has positive relationship with firm performance (measured by ROA and ROE). This suggests that high remuneration is able to motivate and retain directors in order to perform their duty and work harder for the best interest of shareholders. The result also shows all variables affect firm performance differently. For future research, we recommend that this study be expanded using more samples from other industries and other measurement of firm performances such as growth and ratings.
Amplifying Citizens’ Voices in the Face of Media Globalization
Authors: Soler Carmen Echazarreta , Marcé Albert Costa
Published: April 2018

Economic crises have mainly affected the more vulnerable social sectors and created losses of freedom and inequality. Currently, most media are controlled by a relatively small group of companies around the world. In the face of this situation, networked society has accelerated the development of alternative communication models, which act as loudspeakers for citizens’ voices. The aim of this study is to describe the main features of the new forms of citizen expression, communication and cooperation, such as social networks, review sites, citizen journalism and the collaborative economy. It is concluded that in the face of these new challenges it is essential to continue to develop ethical principles of self-regulation to ensure the accuracy and thoroughness of new forms of communication on the Net.
Laboratory Environmental Conditions Influence Patent Inventors’ Creative Self-efficacy
Authors: Wang Shih-Hao , Tsai Chung-Lin , Chang Han-Chao
Published: April 2018

A comfortable experimental environment usually enables stress relief among inventors, allowing them to focus on inventing. However, to facilitate smooth and continuous experimental procedures, the public spaces and computing environments of conventional laboratories are usually replete with heavy instruments and interconnected wires; consequently, inventors have limited space to conduct complex experiments. These public spaces and computing environments negatively affect the creative self-efficacy (CSE) of inventors. Based on CSE theory and modified information layout complexity theory, in this study, 100 inventors who had obtained patents were recruited. The results indicated that a wireless cloud public space and computing environment positively moderated and enhanced the relationship between low layout complexity and inventor CSE; conventional public spaces and computing environments featuring cables negatively moderated and weakened the relationship between high layout complexity and inventor CSE. More than 40% of participants highly supported using one electronic tablet to manipulate multiple instruments. The results also revealed that approximately 64% of participants did not think they were essential in promoting critical mass in the laboratory. This finding was significantly different from the degree centrality of creativity perspective. Critical indicators of inventor CSE were found to be inventors’ decision-making capabilities regarding innovative research directions and their communication skills with supervisors.
Analysis of the VIDAS® Staph Enterotoxin III (SET3) for Detection of Staphylococcal Enterotoxins G, H, and I in Foods
Authors: Hait Jennifer M , Nguyen Angela T , Tallent Sandra M
Published: April 2018

Background: Staphylococcal food poisoning (SFP) frequently causes illnesses worldwide. SFP occurs from the ingestion of staphylococcal enterotoxins (SEs) preformed in foods by enterotoxigenic strains of Staphylococcus species, primarily S. aureus. SEG, SEH, and SEI induce emesis and have been implicated in outbreaks. Immunological-based methods are deemed the most practical methods for the routine analysis of SEs in foods given their ease of use, sensitivity, specificity, and commercial availability. These kits are routinely used to test for SEA-SEE. However, only recently has a kit been developed to detect SEG, SEH, and SEI. Objective: Our research examined the performance of the novel VIDAS® Staph Enterotoxin III (SET3) for the detection of staphylococcal enterotoxins SEG, SEH, and SEI in foods. Methods: Here we assess the sensitivity and specificity of SET3 using duplicate test portions of six foods at varying concentrations of inclusivity and exclusivity inocula: pure SEG, SEH, SEI, S. aureus strain extracts positive for seg, seh, and sei, as well as SEA, SEB, SEC, SED, and SEE. Results: The overall detection limit was less than 2.09 ng/mL for foods inoculated with SEG, SEH, and SEI, with no cross reactivity observed. Highlights: Integrating concurrent testing to detect the presence of SEA–SEE and SEG–SEI utilizing the SET3 along with the VIDAS SET2, Ridascreen® SET total, or other comparable kits will be instrumental for the future food assessments in our laboratory and may become the new standard for SE analysis of foods.
Determination of Alkaloids in Mitragyna speciosa (Kratom) Raw Materials and Dietary Supplements by HPLC-UV: Single-Laboratory Validation, First Action 2017.14
Authors: Mudge Elizabeth M , Brown Paula N
Published: April 2018

The AOAC Expert Review Panel (ERP) approved a method for the quantitation of alkaloids in Mitragyna speciosa for consideration as First Action Official MethodSM status. The previously published method summarized a single-laboratory validation of two alkaloids, mitragynine and 7-hydroxymitragynine, in raw materials and finished products. The methods performance was compared with the AOAC Standard Method Performance Requirement 2015.008. With repeatability precision (RSDr) ranging from 0.51 to 0.95% and recoveries from 93.6 to 98.9% in the different product matrices, the ERP adopted the method and provided recommendations for achieving Final Action status.
Turning Delay Stochastic User Equilibrium Model based on the Weibull Distribution
Authors: Chen Jing , Xu Wenqiang , Peng Weimin , Xing Baixi
Published: April 2018

With the continuous expansion of urban scales and the constant growth of traffic demands, it has become important to accurately predict the distribution of traffic flow so as to relieve the traffic jams and lower the energy consumption. This research mainly focuses on the distribution problem of traffic flow in the urban traffic network. A minimization program has been provided as an alternative formulation for the turning delay stochastic user equilibrium problem. The paper derives the Weibull distribution-based node-link random loading mechanism of turning delay for direct calculation of link and turning flows that are consistent with thepath flow, thus avoiding the enumeration of turning paths. Numerical examples are provided to illustrate the turning delay stochastic user equilibrium (SUE) model and the nodelink- based algorithm. The experiment demonstrates that the present method can reflect the relative performance of link and turning costs well, while presenting its advantages in the simulation of large-scale turning delay flow  ssignment.
A robust method for RNA extraction and purification from a single adult mouse tendon
Authors: Grinstein Mor , Dingwall Heather L. , Shah Rishita R. , Capellini Terence D. , Galloway Jenna L.
Published: April 2018

Background

Mechanistic understanding of tendon molecular and cellular biology is crucial toward furthering our abilities to design new therapies for tendon and ligament injuries and disease. Recent transcriptomic and epigenomic studies in the field have harnessed the power of mouse genetics to reveal new insights into tendon biology. However, many mouse studies pool tendon tissues or use amplification methods to perform RNA analysis, which can significantly increase the experimental costs and limit the ability to detect changes in expression of low copy transcripts.

Methods

Single Achilles tendons were harvested from uninjured, contralateral injured, and wild type mice between three and five months of age, and RNA was extracted. RNA Integrity Number (RIN) and concentration were determined, and RT-qPCR gene expression analysis was performed.

Results

After testing several RNA extraction approaches on single adult mouse Achilles tendons, we developed a protocol that was successful at obtaining high RIN and sufficient concentrations suitable for RNA analysis. We found that the RNA quality was sensitive to the time between tendon harvest and homogenization, and the RNA quality and concentration was dependent on the duration of homogenization. Using this method, we demonstrate that analysis ofScxgene expression in single mouse tendons reduces the biological variation caused by pooling tendons from multiple mice. We also show successful use of this approach to analyzeSox9andCol1a2gene expression changes in injured compared with uninjured control tendons.

Discussion

Our work presents a robust, cost-effective, and straightforward method to extract high quality RNA from a single adult mouse Achilles tendon at sufficient amounts for RT-qPCR as well as RNA-seq. We show this can reduce variation and decrease the overall costs associated with experiments. This approach can also be applied to other skeletal tissues, as well as precious human samples.
Association between vitamin D concentrations and knee pain in patients with osteoarthritis
Authors: Cakar Murat , Ayanoglu Semih , Cabuk Haluk , Seyran Metin , Dedeoglu Suleyman Semih , Gurbuz Hakan
Published: April 2018

Objectives

Osteoarthritis (OA) and vitamin D deficiency are common health conditions in older people. Whether vitamin D concentration is associated with knee OA is controversial. In this study, we aimed to determine the association between serum concentrations of vitamin D and osteoarthritic knee pain.

Subjects and Methods

Vitamin D concentrations were measured with the 25 hydroxyvitamin D test in patients presenting with clinical symptoms of primary knee osteoarthritis. Osteoarthritis was graded on the Kellgren-Lawrence grading scale from anteroposterior and lateral radiographs. Height, weight, and body mass index (BMI) were recorded. Patients completed a 10-cm visual analogue scale (VAS) for indicating pain and the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Vitamin D concentration was defined as severely deficient (<10 ng/mL), insufficient (10 to 19 ng/mL), or normal (20 to 50 ng/mL).

Results

Of 149 patients (133 women), the mean age was 63.6 years. Mean vitamin D concentration was 11.53 ng/mL, and 90% patients were vitamin D deficient. Mean WOMAC score was 57.2, and VAS pain score was 7.5. Kellgren-Lawrence grade was 2 for 10 patients, grade 3 for 61, and grade 4 for 88. Mean BMI was 33.4. Mean values of VAS, WOMAC, and BMI did not differ by vitamin D status.

Conclusion

Serum vitamin D concentration is not associated with knee pain in patients with osteoarthritis.
Engineering isoprene synthesis in cyanobacteria
Authors: Chaves Julie E. , Melis Anastasios
Published: April 2018

The renewable production of isoprene (Isp) hydrocarbons, to serve as fuel and synthetic chemistry feedstock, has attracted interest in the field recently. Isp (C5H8) is naturally produced from sunlight, CO2 and H2O photosynthetically in terrestrial plant chloroplasts via the terpenoid biosynthetic pathway and emitted in the atmosphere as a response to heat stress. Efforts to institute a high capacity continuous and renewable process have included heterologous expression of the Isp synthesis pathway in photosynthetic microorganisms. This review examines the premise and promise emanating from this relatively new research effort. Also examined are the metabolic engineering approaches applied in the quest of renewable Isp hydrocarbons production, the progress achieved so far, and barriers encountered along the way.
Crystal structure of phosphomannose isomerase from Candida albicans complexed with 5‐phospho‐d‐arabinonhydrazide
Authors: Ahmad Lama , Plancqueel Stéphane , Dubosclard Virginie , Lazar Noureddine , Ghattas Wadih , Li de la Sierra‐Gallay Inès , van Tilbeurgh Herman , Salmon Laurent
Published: April 2018

Type I phosphomannose isomerases (PMIs) are zinc‐dependent monofunctional metalloenzymes catalysing the reversible isomerization of d‐mannose 6‐phosphate to d‐fructose 6‐phosphate. 5‐Phospho‐d‐arabinonhydrazide (5PAHz), designed as an analogue of the enediolate high‐energy intermediate, strongly inhibits PMI from Candida albicans (CaPMI). In this study, we report the 3D crystal structure of CaPMI complexed with 5PAHz at 1.85 Å resolution. The high‐resolution structure suggests that Glu294 is the catalytic base that transfers a proton between the C1 and C2 carbon atoms of the substrate. Bidentate coordination of the inhibitor explains the stereochemistry of the isomerase activity, as well as the absence of both anomerase and C2‐epimerase activities for Type I PMIs. A detailed mechanism of the reversible isomerization is proposed.
2‐Methoxypropanol‐1 [MAK Value Documentation in German language, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: April 2018

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) for 2‐methoxypropanol‐1 [
1589‐47‐5
]. Available publications and unpublished study reports are described in detail.

Critical effects of 2‐methoxypropanol‐1 are its irritancy and teratogenicity. A MAK value of 5 ml/m
3
had been set. By analogy with 2‐methoxypropylacetate‐1, this value is now reaffirmed.

Also, by analogy with 2‐methoxypropylacetate‐1 Peak Limitation Category I with excursion factor of 2 is set. 2‐Methoxypropanol‐1 ether remains assigned to Pregnancy Risk Group B and also remains designated with an “H” (for substances that can be absorbed through the skin in toxicologically relevant amounts).
Acetonitril [MAK Value Documentation in German language, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: April 2018

Acetonitrile causes an increased incidence of liver adenomas and carcinomas in rats at 400 ml/m
3
with a statistically significant trend. The number of basophilic foci in the liver is positively correlated with the exposure concentration. At 100 ml/m
3
the elevation is not statistically significant, however, these foci are regarded as preneoplastic lesions. From this concentration the former MAK value of 20 ml/m
3
was derived. It is now lowered to 10 ml/m
3
taking into account the increased respiratory volume at the workplace because the blood:air partition coefficient of acetonitrile is > 5 (see List of MAK and BAT values, chapters I b and I c). Since a systemic effect is critical, Peak Limitation Category II is retained. As the effects are probably due to the metabolites, the default excursion factor of 2 is confirmed despite the long half‐life of acetonitrile.

For rabbits, the NOAEL for developmental toxicity after gavage is 15 mg/kg body weight and day. After toxicokinetic scaling this dose corresponds to a concentration of 34 ml/m
3
at the workplace. Rabbits are more sensitive to acetonitrile than rats and humans and the developmental toxicity of acetonitrile is higher after gavage than after inhalation exposure as shown with rats. Therefore, the rabbit gavage data are not used to assign a Pregnancy Risk Group. The NOAEC for developmental toxicity in rats is 1600 ml/m
3
and after considering the increased respiratory volume at the workplace the difference to the MAK value is sufficient. Therefore, damage to the embryo or foetus is unlikely when the MAK value is observed and acetonitrile remains assigned to Pregnancy Risk Group C.
Methacrylic acid [MAK Value Documentation, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: April 2018

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of methacrylic acid of 5 ml/m3, considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effects of methacrylic acid are goblet cell hyperplasia/hypertrophy in the respiratory epithelia and reduced body weight gain in rats, probably a secondary effect of the irritation at 350 ml/m3in a 90‐day study. Since 2014 the Commission uses an empirical approach to set MAK‐values for substances with critical effects on the upper respiratory tract or the eyes. According to this approach, the NOAEC of 100 ml/m3corresponds to a work place air concentration of 33 ml/m3. As the goblet cell hyperplasia is judged to be adaptive and its incidence is not significantly increased, the MAK value is elevated to 50 ml/m3. Since local effects are critical, the assignment to Peak Limitation Category I and the excursion factor 2 are confirmed. Studies with the read‐across methyl methacrylate which is cleaved to methacrylic acid show that damage to the embryo or foetus is unlikely when the MAK value for methacrylic acid is observed, and the assignment to pregnancy risk group C is confirmed. Methacrylic acid and methyl methacrylate are not genotoxic. Carcinogenicity studies with methacrylic acid are lacking but methyl methacrylate is not carcinogenic. Skin contact does not contribute significantly to systemic toxicity and sensitization is not expected.
Highly Efficient Photocatalytic Hydrogen Evolution by ReS2 via a Two‐Electron Catalytic Reaction
Authors: Zhang Qin , Wang Wenjie , Zhang Jiaqian , Zhu Xiaohui , Zhang Qiqi , Zhang Yujing , Ren Zemian , Song Shuaishuai , Wang Jinming , Ying Zihao , Wang Rui , Qiu Xiaohui , Peng Tianyou , Fu Lei
Published: April 2018

Highly efficient photocatalytic hydrogen evolution (PHE) is highly desirable for addressing the global energy crisis and environmental problems. Although much attention has been given to electron–hole separation, ridding photocatalysts of poor efficiency remains challenging. Here, a two‐electron catalytic reaction is developed by utilizing the distinct trion behavior of ReS2 and the efficient reduction of two H+ (2H+ + 2e− → H2) is realized. Due to the monolayer‐like structure of the catalyst, the free electrons in ReS2 can be captured by the tightly bound excitons to form trions consisting of two electrons and one hole. These trions can migrate to the surface and participate in the two‐electron reaction at the abundant active sites. As expected, such a two‐electron catalytic reaction endows ReS2 with a PHE rate of 13 mmol g−1 h−1 under visible light irradiation. Meanwhile, this reaction allows the typically poor PHE efficiency of pure transition metal dichalcogenides to be overcome. The proposed two‐electron catalytic reaction provides a new approach to the design of photocatalysts for PHE.
Mechanochemical‐Assisted Synthesis of High‐Entropy Metal Nitride via a Soft Urea Strategy
Authors: Jin Tian , Sang Xiahan , Unocic Raymond R. , Kinch Richard T. , Liu Xiaofei , Hu Jun , Liu Honglai , Dai Sheng
Published: April 2018

Crystalline high‐entropy ceramics (CHC), a new class of solids that contain five or more elemental species, have attracted increasing interest because of their unique structure and potential applications. Up to now, only a couple of CHCs (e.g., high‐entropy metal oxides and diborides) have been successfully synthesized. Here, a new strategy for preparing high‐entropy metal nitride (HEMN‐1) is proposed via a soft urea method assisted by mechanochemical synthesis. The as‐prepared HEMN‐1 possesses five highly dispersed metal components, including V, Cr, Nb, Mo, Zr, and simultaneously exhibits an interesting cubic crystal structure of metal nitrides. By taking advantage of these unique features, HEMN‐1 can function as a promising candidate for supercapacitor applications. A specific capacitance of 78 F g−1 is achieved at a scan rate of 100 mV s−1 in 1 m KOH. In addition, such a facile synthetic strategy can be further extended to the fabrication of other types of HEMNs, paving the way for the synthesis of HEMNs with attractive properties for task‐specific applications.
Stereospecific Nucleophilic Substitution with Arylboronic Acids as Nucleophiles in the Presence of a CONH Group
Authors: Tian Duanshuai , Li Chengxi , Gu Guoxian , Peng Henian , Zhang Xumu , Tang Wenjun
Published: April 2018

Stereospecific nucleophilic substitution was achieved for the first time with arylboronic acids as nucleophiles. This transition‐metal‐free coupling between chiral α‐aryl‐α‐mesylated acetamides and arylboronic acids provided access to a series of chiral α,α‐diaryl acetamides with excellent enantioselectivity and moderate to good yields. The CONH functionality proved to be crucial for bridging the reactants and promoting the reaction. Efficient syntheses of a cannabinoid CB1 receptor ligand, the antidepressant (S)‐diclofensine, and a key chiral building block of the inhibitor implitapide were successfully accomplished by using this method.
Fucose Migration in Intact Protonated Glycan Ions: A Universal Phenomenon in Mass Spectrometry
Authors: Mucha Eike , Lettow Maike , Marianski Mateusz , Thomas Daniel A. , Struwe Weston B. , Harvey David J. , Meijer Gerard , Seeberger Peter H. , von Helden Gert , Pagel Kevin
Published: April 2018

Fucose is an essential deoxysugar that is found in a wide range of biologically relevant glycans and glycoconjugates. A recurring problem in mass spectrometric analyses of fucosylated glycans is the intramolecular migration of fucose units, which can lead to erroneous sequence assignments. This migration reaction is typically assigned to activation during collision‐induced dissociation (CID) in tandem mass spectrometry (MS). In this work, we utilized cold‐ion spectroscopy and show for the first time that fucose migration is not limited to fragments obtained in tandem MS and can also be observed in intact glycan ions. This observation suggests a possible low‐energy barrier for this transfer reaction and generalizes fucose migration to an issue that may universally occur in any type of mass spectrometry experiment.
Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High pH Dynamic Kinetic Reduction
Authors: Xu Feng , Kosjek Birgit , Cabirol Fabien L. , Chen Haibin , Desmond Richard , Park Jeonghan , Gohel Anupam P. , Collier Steven J. , Smith Derek J. , Liu Zhuqing , Janey Jacob M. , Chung John Y. L. , Alvizo Oscar
Published: April 2018

Described here is an efficient stereoselective synthesis of vibegron enabled by an enzymatic dynamic kinetic reduction that proceeds in a high‐pH environment. To overcome enzyme performance limitations under these conditions, a ketoreductase was evolved by a computationally and structurally aided strategy to increase cofactor stability through tighter binding.
Fluorimetric determination of febuxostat in dosage forms and in real human plasma via Förster resonance energy transfer
Authors: El‐Gizawy Samia M. , Atia Noha N. , Hosny Noha M.
Published: April 2018

A rapid, simple, selective and precise fluorimetric method was developed and validated for determination of a selective xanthine oxidase inhibitor; febuxostat (FBX) in pharmaceutical formulations and in human plasma. The proposed method is based on quenching effect of FBX on the fluorescence intensity of terbium (Tb3+) through fluorescence resonance energy transfer (FRET) from Tb3+ to FBX. The formed complex was measured at λex. 320 nm/λem. 490 nm against a reagent blank. Fluorescence intensity of Tb3+ was diminished when FBX was added. A linear relationship between the fluorescence quenching value of the formed complex
and the concentration of FBX was investigated. The reaction conditions and the fluorescence spectral properties of the complex have been studied. The linearity range of the developed method was 1.0–16.0 μg/ml. The suggested method was applied successfully for the estimation of FBX in bulk powder, dosage forms and spiked plasma samples with excellent recoveries (96.79–98.89%). In addition, the developed method has been successfully applied for determination of FBX in real plasma samples collected from healthy volunteers with good recoveries (82.06–85.65%). All obtained results of the developed method were statistically analyzed and validated according to ICH (International Conference on Harmonization) guidelines.
The pharmacokinetics and tissue distribution of curcumin and its metabolites in mice
Authors: Wang Junjun , Yu Xuejin , Zhang Ling , Wang Ling , Peng Zhihong , Chen Yong
Published: April 2018

Curcumin (CUR) is the major active component of turmeric and plays an important role in the prevention and treatment of many chronic diseases such as respiratory and neurodegenerative disease. In the present work, a rapid and simple LC–MS/MS method was developed to investigate the pharmacokinetics and tissue distribution of CUR and its metabolites in mice after intravenous administration of CUR (20 mg/kg). The results showed that the values of AUC0–∞ were 107.0 ± 18.3, 6.0 ± 1.2 and 12.0 ± 4.0 (mg/L) min, and those for t1/2z were 32.4 ± 10.8, 6.4 ± 2.4 and 5.6 ± 1.8 min for CUR, dihydrocurcumin (DHC) and tetrahydrocurcumin (THC) in plasma, respectively. CUR and THC could be detected in liver while CUR and DHC were detected in kidney. Only CUR was detected in brain. These findings indicated that THC was the main metabolite of CUR in plasma. The exposure of CUR in plasma was 6‐fold greater than that in liver, kidney and brain.
Supported Molecular Catalysts
Authors: Pagliaro Mario , Sels Bert F.
Published: April 2018

This Editorial presents the Special Issue on Supported Molecular Catalysts as a forum to discuss recent advances in the immobilization and heterogenization of molecular catalysts. The scope ranges from organic synthesis and highly selective reactions through to photocatalysis and electrocatalysis, including advances in enzyme immobilization methodology. The outcome is a wide spectrum of papers encompassing all the old formal domains of catalysis research of both primary and secondary research.
The Role of Onium Salts in the Pro‐Oxidant Effect of Gold Nanoparticles in Lipophilic Environments
Authors: Baschieri Andrea , Del Secco Benedetta , Zaccheroni Nelsi , Valgimigli Luca , Amorati Riccardo
Published: April 2018

Metal nanoparticles are reported to be toxic due to the generation of free radicals at their surface. Relatively inert thiol‐capped gold nanoparticles (AuNPs) have been reported to induce radical formation in the presence of hydroperoxides, which would conflict with their potential use as inert scaffolds for the design of novel nano‐antioxidants. With the aim of clarifying this aspect, we investigated the pro‐oxidant activity of dodecanethiol‐capped AuNPs (∼5 nm diameter), prepared through the Brust–Schiffrin synthesis, by oxygen‐uptake kinetic studies. The pro‐oxidant activity was found to be proportional to the impurities of the transfer agent tetraoctylammonium bromide (TOAB) left from the synthesis and decreased on repeated washing of the nanoparticles. Under identical settings similar batches of AuNP (∼9 nm diameter) prepared through the Ulman method without onium salts showed no pro‐oxidant behavior. The alternative onium phase‐transfer agents Oct4NBF4 (Oct=octyl), Hex4NBF4 (Hex=hexyl), and Hex4NPF6 were comparatively investigated and showed lower pro‐oxidant activity depending on the counterion (Br−>PF6−>BF4−).
Peripherally Metalated Porphyrins with Applications in Catalysis, Molecular Electronics and Biomedicine
Authors: Longevial Jean‐François , Clément Sébastien , Wytko Jennifer A. , Ruppert Romain , Weiss Jean , Richeter Sébastien
Published: April 2018

Porphyrins are conjugated, stable chromophores with a central core that binds a variety of metal ions and an easily functionalized peripheral framework. By combining the catalytic, electronic or cytotoxic properties of selected transition metal complexes with the binding and electronic properties of porphyrins, enhanced characteristics of the ensemble are generated. This review article focuses on porphyrins bearing one or more peripheral transition metal complexes and discusses their potential applications in catalysis or biomedicine. Modulation of the electronic properties and intramolecular communication through coordination bond linkages in bis‐porphyrin scaffolds is also presented.
Current Advances in Semiconductor Nanomaterial‐Based Photoelectrochemical Biosensing
Authors: Zang Yang , Fan Jing , Ju Yun , Xue Huaiguo , Pang Huan
Published: April 2018

Photoelectrochemical (PEC) analysis is a new detection technique developed in recent years, which has the advantages of high sensitivity, low background signal and desirable selectivity, obtaining the great progress in sensing applications. Semiconductor nanomaterials with excellent photoelectric activity have played a vital role in the construction of PEC sensing platform. Thus, this Review introduces the recent advances of semiconductor nanomaterials‐based PEC analysis, and describes the typical PEC sensing strategies. Some representative nanomaterials, including metallic oxides, metallic sulfides, graphitic carbon nitride, transition‐metal dichalcogenides and quantum dots, are summarized for advanced PEC devices, as well as their applications in nucleic acid analysis, immunoassays, cell detection, protein and enzyme sensing, and small biomolecule monitoring. Finally, some future opportunities and challenges of PEC biosensing are also discussed.
Single‐Molecule Force Spectroscopy Reveals Self‐Assembly Enhanced Surface Binding of Hydrophobins
Authors: Li Bing , Wang Xin , Li Ying , Paananen Arja , Szilvay Géza R. , Qin Meng , Wang Wei , Cao Yi
Published: April 2018

Hydrophobins have raised lots of interest as powerful surface adhesives. However, it remains largely unexplored how their strong and versatile surface adhesion is linked to their unique amphiphilic structural features. Here, we develop an AFM‐based single‐molecule force spectroscopy assay to quantitatively measure the binding strength of hydrophobin to various types of surfaces both in isolation and in preformed protein films. We find that individual class II hydrophobins (HFBI) bind strongly to hydrophobic surfaces but weakly to hydrophilic ones. After self‐assembly into protein films, they show much stronger binding strength to both surfaces due to the cooperativity of different interactions at nanoscale. Such self‐assembly enhanced surface binding may serve as a general design principle for synthetic bioactive adhesives.
Role of metastasis‐directed treatment in kidney cancer
Authors: Psutka Sarah P. , Master Viraj A.
Published: April 2018

Despite the rapid elaboration of multiple, novel systemic agents introduced for metastatic renal cell carcinoma (mRCC) in recent years, a durable complete response remains elusive with systemic therapy alone. Definitive treatment of the metastatic deposit remains the sole potentially curative option and is a cornerstone of mRCC therapy, offering potential for both local control and palliation of tumor‐related symptoms. In this review, the evidence supporting the definitive treatment of mRCC is examined and summarized, including the use of surgical metastasectomy, thermal ablation, radiotherapy, and other minimally invasive options. Multimodal approaches, including the combination of metastasectomy with novel systemic agents, are discussed. Finally, the authors review considerations for patient selection for this type of therapy and summarize available risk‐stratification tools that may help guide shared decision making.
Comparative Pharmacokinetics and Pharmacodynamics of Bococizumab Following a Single Subcutaneous Injection Using Drug Substance Manufactured at Two Sites or Administration via Two Different Devices
Authors: Wang Ellen Q. , Plotka Anna , Salageanu Joanne , Baltrukonis Daniel , Mridha Khurshid , Frederich Robert , Sullivan Beth E.
Published: April 2018

The pharmacokinetics (PK) and pharmacodynamics (PD) of bococizumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, were compared following a single 150‐mg subcutaneous dose administered to healthy subjects (n = 156–158/arm) via: (1) a prefilled syringe (PFS) using drug substance (DS) manufactured by Pfizer, (2) a PFS using DS manufactured by Boehringer Ingelheim Pharma, (3) a prefilled pen using DS manufactured by Pfizer (NCT02458209). Blood samples were collected for 12 weeks postdose. Safety was monitored throughout. Mean maximum plasma concentration (Cmax) ranged between 11.0 and 11.3 μg/mL, and area under the plasma concentration‐time curve (AUCinf) ranged between 177.6 and 185.0 μg·day/mL across treatments. The 90% confidence intervals for the ratios of adjusted geometric means for Cmax and AUCinf fell within the 80%–125% range for both DS and delivery device comparisons. Comparable low‐density lipoprotein cholesterol profiles were observed, with nadir values of 54.3–56.1 mg/dL across treatments. Similar PCSK9 responses were also observed. Safety profiles were similar across treatments, and the majority of adverse events (AEs) were mild. Three subjects reported serious AEs. The most frequently reported AEs were headache, injection‐site reaction, and upper respiratory tract infection, with no clear differences across treatments. Comparable PK, PD, and safety were observed following a single bococizumab 150‐mg subcutaneous injection regardless of site of DS manufacture or delivery device used.