bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity of dispersed oil on Gold–saddle rabbitfish Siganus guttatus fry
Authors: Balisco Rodulf Anthony , Quinitio Gerald
Published: July 2024

The acute toxicity of dispersant Mardeus-455 added to water accommodated fractions (WAF) were evaluated in Gold-saddle rabbitfish Siganus guttatus fry after 72 h exposure under laboratory conditions. Mortalities of fry exposed to different concentrations of dispersed oil were recorded every hour for the first 6 h, every 3 h for the next 12 h, and every 6 h thereafter. Results showed that the higher the ratio of dispersant and WAF, the higher the mortality of the rabbitfish fry which may be due to the enhanced availability of polyaromatic hydrocarbons (PAH). The LC50 was computed at 3.692% of the oil volume. The application of dispersant in cleaning oil spills must be limited to reduce its harmful effect in the marine environment. Assessing toxicity of dispersed oil in fish fry may help understand the extent of environmental damage after cleaning oil spill using dispersant.
JENIS SATWA BURUNG PADA KOMUNITAS MANGROVE DI TELUK HITU KABUPATEN MALUKU TENGAH
Authors: Sasole Aldi , Badaruddin Ernywati , Kaya Manuel
Published: July 2024

This research aims to determine the types of bird species in the mangrove area in Hitu Bay, Central Maluku Regency. The method used in this research is descriptive using direct and indirect census techniques to determine the type and distribution of birds. The results of the research show that in Hitu Bay there are 17 species of birds, consisting of 12 species of terrestrial birds and 5 species of seabirds. The bird distribution value with the lowest frequency is 0.1 and the lowest relative frequency is 1.03, namely the Common turtledove (Streptopelia chinensis), while the highest frequency is 0.9 and the highest relative frequency is 9.27, namely the Cow swallow (Collocalia esculenta), Little egret (Egretta garzetta), and Cucak kutilang (Pycnonotus aurigaster).
Labyrinthes de la nouvelle violence urbaine dans les romans québécois
Authors: Soares de Souza Licia
Published: July 2024

Dans la littérature, la notion de précarité est maintes fois analysée avec certains lieux communs de notre époque, comme les figures de l’exil et de la pérégrination, nous dit Simon Harel (2007,53). Il ajoute qu’une poétique diffuse de la postmodernité affirme que nos espaces sont éphémères, que nos actions n’ont pas de véritable portée sociale, que le monde des traditions est peu à peu abandonné. Ainsi l’art n’existerait que dans son incomplétude radicale et la négativité serait notre nouvelle appartenance. Cet article analyse l’émergence de la précarité post-moderne dans des romans québécois contemporains qui utilisent des personnages enfants pour signaler les noyaux thématiques de l’incomplétude symbolique de la société québécoise. post-référendaire Les écrivains Sylvain Trudel, Christian Mistral, Marie Gagnon, Henri Lamoureux et Bertrand Gervais réussissent à montrer comment des enfants romanesques évoluent dans une société fragmentée, elle même sans répères, si ce n’est celui de la réussite individuelle basée sur les valeurs de l’argent et du profit.
Optimalisasi Mekanisme pada Lifeboat dalam Menanggulangi Kegagalan Launching di KM. Kaltim Express22
Authors: Ismail Muhammad Rizqy , Suriadi Suriadi , Siskia Syafni Yelvi , Sulistiana Oktavera , Kurniadi Dedy
Published: July 2024

Dalam perkembangannya industri transportasi laut yang pesat tidak terlepas dari resiko kecelakaan kerja yang cukup tinggi. Timbulnya kasus kecelakaan yang terjadi di atas kapal disebabkan karena kesalahan dan kelalaian manusianya serta minimnya pelatihan keselamatan, selebihnya disebabkan oleh faktor alam dan faktor faktor lainnya. Penelitian tersebut di lakukan bertujuan untuk mengetahui penghambat saat menurunkan sekoci serta cara yang tepat agar awak kapal dapat menurunkan sekoci penolong dengan optimal. Penelitian ini adalah kualitatif dengan metode deskriptif. Lokasi penelitian ini adalah di atas kapal KM. Kaltim Express22. Teknik Pengumpulan data adalah menggunakan teknik observasi, wawancara dan dokumentasi. Hasil dari penelitian yang dilakukan penulis adalah ada beberapa kendala yang dihadapi awak kapal dalam latihan menurunkan sekoci penolong yaitu kurangnya perawatan dan  ketidaksiapan awak kapal dalam latihan, serta anggapan hanya sekedar latihan membuat respon dalam tugas-tugas penurunan sekoci kurang diperhatikan.
speculative photography. an attempt (essay) of making visible (manifesto)
Authors: Cramer Florian
Published: July 2024

This essay and manifesto define speculative photography from a historical perspective and through practical poetics, as photography that integrates fantastic and experimental elements in both its subjects and processes. Such photography is even more urgent at a time when generative artificial intelligence (AI) and computational photography are driving photography to an impasse of fabricated yet all-pervasive realism. The text defines speculative photography in its semiotic and information-theory aspects, outlines a taxonomy of speculative qualities in photography alongside examples of photographers and photographic communities practicing them, and pays particular attention to contemporary subcultures of early-2000s digital camera (digicam) reuse and internet pop-cultural redefinitions of “aesthetics”. While theories and definitions of speculative photography have existed since the 1970s, they are scattered and cover only select aspects of the broader concept proposed here. This paper argues that speculative photography rejects empiricism and notions of truth while practicing an art of the “medium” in its most literal – physical, artistic and spiritual – meanings.
Speech and music recruit frequency-specific distributed and overlapping cortical networks
Authors: te Rietmolen Noémie , Mercier Manuel R , Trébuchon Agnès , Morillon Benjamin , Schön Daniele
Published: July 2024

To what extent does speech and music processing rely on domain-specific and domain-general neural networks? Using whole-brain intracranial EEG recordings in 18 epilepsy patients listening to natural, continuous speech or music, we investigated the presence of frequency-specific and network-level brain activity. We combined it with a statistical approach in which a clear operational distinction is made between shared, preferred, and domain-selective neural responses. We show that the majority of focal and network-level neural activity is shared between speech and music processing. Our data also reveal an absence of anatomical regional selectivity. Instead, domain-selective neural responses are restricted to distributed and frequency-specific coherent oscillations, typical of spectral fingerprints. Our work highlights the importance of considering natural stimuli and brain dynamics in their full complexity to map cognitive and brain functions.
Anomaly prediction of Internet behavior based on generative adversarial networks
Authors: Wang XiuQing , An Yang , Hu Qianwei
Published: July 2024

With the popularity of Internet applications, a large amount of Internet behavior log data is generated. Abnormal behaviors of corporate employees may lead to internet security issues and data leakage incidents. To ensure the safety of information systems, it is important to research on anomaly prediction of Internet behaviors. Due to the high cost of labeling big data manually, an unsupervised generative model–Anomaly Prediction of Internet behavior based on Generative Adversarial Networks (APIBGAN), which works only with a small amount of labeled data, is proposed to predict anomalies of Internet behaviors. After the input Internet behavior data is preprocessed by the proposed method, the data-generating generative adversarial network (DGGAN) in APIBGAN learns the distribution of real Internet behavior data by leveraging neural networks’ powerful feature extraction from the data to generate Internet behavior data with random noise. The APIBGAN utilizes these labeled generated data as a benchmark to complete the distance-based anomaly prediction. Three categories of Internet behavior sampling data from corporate employees are employed to train APIBGAN: (1) Online behavior data of an individual in a department. (2) Online behavior data of multiple employees in the same department. (3) Online behavior data of multiple employees in different departments. The prediction scores of the three categories of Internet behavior data are 87.23%, 85.13%, and 83.47%, respectively, and are above the highest score of 81.35% which is obtained by the comparison method based on Isolation Forests in the CCF Big Data & Computing Intelligence Contest (CCF-BDCI). The experimental results validate that APIBGAN predicts the outlier of Internet behaviors effectively through the GAN, which is composed of a simple three-layer fully connected neural networks (FNNs). We can use APIBGAN not only for anomaly prediction of Internet behaviors but also for anomaly prediction in many other applications, which have big data infeasible to label manually. Above all, APIBGAN has broad application prospects for anomaly prediction, and our work also provides valuable input for anomaly prediction-based GAN.
Automated machine learning for fabric quality prediction: a comparative analysis
Authors: Metin Ahmet , Bilgin Turgay Tugay
Published: July 2024

The enhancement of fabric quality prediction in the textile manufacturing sector is achieved by utilizing information derived from sensors within the Internet of Things (IoT) and Enterprise Resource Planning (ERP) systems linked to sensors embedded in textile machinery. The integration of Industry 4.0 concepts is instrumental in harnessing IoT sensor data, which, in turn, leads to improvements in productivity and reduced lead times in textile manufacturing processes. This study addresses the issue of imbalanced data pertaining to fabric quality within the textile manufacturing industry. It encompasses an evaluation of seven open-source automated machine learning (AutoML) technologies, namely FLAML (Fast Lightweight AutoML), AutoViML (Automatically Build Variant Interpretable ML models), EvalML (Evaluation Machine Learning), AutoGluon, H2OAutoML, PyCaret, and TPOT (Tree-based Pipeline Optimization Tool). The most suitable solutions are chosen for certain circumstances by employing an innovative approach that finds a compromise among computational efficiency and forecast accuracy. The results reveal that EvalML emerges as the top-performing AutoML model for a predetermined objective function, particularly excelling in terms of mean absolute error (MAE). On the other hand, even with longer inference periods, AutoGluon performs better than other methods in measures like mean absolute percentage error (MAPE), root mean squared error (RMSE), and r-squared. Additionally, the study explores the feature importance rankings provided by each AutoML model, shedding light on the attributes that significantly influence predictive outcomes. Notably, sin/cos encoding is found to be particularly effective in characterizing categorical variables with a large number of unique values. This study includes useful information about the application of AutoML in the textile industry and provides a roadmap for employing Industry 4.0 technologies to enhance fabric quality prediction. The research highlights the importance of striking a balance between predictive accuracy and computational efficiency, emphasizes the significance of feature importance for model interpretability, and lays the groundwork for future investigations in this field.
Genetic variation for tolerance to pre-harvest sprouting in mungbean (Vigna radiata) genotypes
Authors: Gupta Soma , Aski Muraleedhar , Mishra Gyan Prakash , Yadav Prachi S. , Tripathi Kuldeep , Lal Sandeep Kumar , Jain Simran , Nair Ramakrishnan Madhavan , Dikshit Harsh Kumar
Published: July 2024

Pre-harvest sprouting (PHS) is one of the important abiotic stresses in mungbean which significantly reduces yield and quality of the produce. This study was conducted to evaluate the genetic variability for tolerance to pre-harvest sprouting in diverse mungbean genotypes while simultaneously deciphering the association of yield contributing traits with PHS. Eighty-three diverse mungbean genotypes (23 released varieties, 23 advanced breeding lines and 37 exotic germplasm lines) were investigated for tolerance to PHS, water imbibition capacities by pods, pod and seed physical traits. Wide variation in PHS was recorded which ranged between 17.8% to 81% (mean value 54.34%). Germplasm lines exhibited higher tolerance to PHS than the high-yielding released varieties. Correlation analysis revealed PHS to be positively associated with water imbibition capacity by pods (r = 0.21) and germinated pod % (r = 0.78). Pod length (r = −0.13) and seeds per pod (r = −0.13) were negatively influencing PHS. Positive associations between PHS and water imbibition capacity by pods, germinated pod % and 100-seed weight was further confirmed by multivariate analysis. Small-seeded genotypes having 100-seed weight <3 g exhibited higher tolerance to PHS compared to bold-seeded genotypes having 100-seed weight more than 3.5 g. Fresh seed germination among the selected PHS tolerant and susceptible genotypes ranged from 42% (M 204) to 98% (Pusa 1131). A positive association (r = 0.79) was recorded between fresh seed germination and PHS. Genotypes M 1255, M 145, M 422, M 1421 identified as potential genetic donors against PHS could be utilized in mungbean breeding programs.
Contexto atual sobre as pesquisas relacionadas a psicologia do trânsito
Authors: Bachinski Genecy Roberto dos Santos , Queiroz José Orlando da Silva , Neves Keyla Suellen Rocha , Gonçalves Natanael Barros , Ribeiro Camila Gonçalves , Silva Priscilla Andrade
Published: July 2024

Atualmente as atividades que envolvem a psicologia do trânsito prevalece atrelada à avaliação psicológica. No entanto, a psicologia requer disciplina espcifica pririzando a segurança no trânsito, uma vez que os condutores representam o fator prepodenderante nos casos de acidentes de trânsito no território brasileiro. Diante o exposto, uma revisão de literatura foi realizada, sendo incluídos estudos conduzidos no Brasil, retrospectivos e prospectivos que abordassem sobre a importância da psicologia no trânsito. Foram compilados artigos das bases de dados do Portal de Periódicos Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes), além de literaturas referentes à psicologia no trânsito. As análises das literaturas ocorreram devido à aproximação da temática da prática psicológica no trânsito. Pelos documentos selecionados, foram examinadas as questões dos acidentes, educação, prevenção, avaliação psicológica, perícias, qualidade do sono e contexto frente a pandemia da Covid-19. Os resultados revelam que a relação entre psicologia do trânsito e educação tem sido destacada a partir de diversos contextos, públicos, abordagem teórica e metodologias. Percebe-se que as pesquisas indicam que a abordagem educacional voltada a psicologia do trânsito precisa considerar as questões do trânsito como um contexto social. Os artigos ressaltam a notoriedade de as práticas psicológicas conversarem com outras áreas de conhecimento, dessa maneira ressalta a pluridisciplinariedade compreendida nas estratégias educativas, de intervenção e prevenção.
Treatment Satisfaction and Quality of Life Changes in Patients Receiving Conventional Fixed Orthodontic Appliances and Clear Aligner Therapy: A Questionnaire Based Cross-sectional Study
Authors: Marusamy Kavitha Odathurai , Ramasamy Saravanan , Fitaihi Elaf Jamal , Fallatah Rawaa , Althahafi Dhuha
Published: July 2024

Introduction: The orthodontic outcome is mainly decided by the objective evaluation by orthodontists with minimal subjective considerations. Although there is increasing patient acceptance of orthodontic aligners for malocclusion treatment, minimal evidence exists regarding their efficacy and adverse effects compared to conventional fixed orthodontic appliances. Aim: To assess patient satisfaction and quality of life changes after these two modalities of orthodontic treatment and to analyse the influencing co-factors. Materials and Methods: A web-based three-part questionnaire survey was done amongst 303 participants who underwent either fixed orthodontic therapy or invisalign treatment. The first part collected the participants’ demographic details and their treatment type. The second part of five questions addressed their preferences, facilitators, and factors preventing them from undergoing orthodontic treatment. The final part of ten questions measured the satisfaction ratio on a five-point Likert scale. Descriptive statistics were computed to provide an overview of responses using frequencies and percentages. Inferential statistics were computed using the chi-square test, and a p-value less than 0.05 was considered statistically significant. Results: This study of 303 orthodontic patients found no significant difference in overall satisfaction between fixed braces and clear aligners (p=0.989), although aligners were favoured for facial appearance, increased treatment costs were a concern for the majority. Female participants (185, 61.1%) constituted the majority of the participants, with 178 (58.7%) aged between 19- 29 years. Clear aligner users experienced more discomfort with additional visits and appointment booking, while fixed braces users had greater concerns about appearance and increased brushing time. Younger patients reported higher satisfaction across several treatment aspects (p=0.013). Men were more satisfied with treatment duration and costs than women. Conclusion: In conclusion, while clear aligners provide aesthetic and hygiene benefits, overall satisfaction was comparable to fixed braces, with cost being a significant factor. Comprehensive consultations are essential to align treatment with patient needs. Future research should involve larger, more diverse samples for validation.
Biochemical Defense Responses in Advanced Backcross-derived Rice Genotypes to Nilaparvata lugens (Stal) Infestation
Authors: Kumari R. Prathima , Anusha Ch. , Kumar R. Shravan , Prasad K. Rajendra , Hari Y. , Gowda M. A. Prajwal , Akhilandeshwari D.
Published: July 2024

BPH, Nilaparvata lugens (Delphacidae: Homoptera) infestation on most of the resistant and moderately resistant backcross derived rice genotypes and resistant checks (PTB 33 and BM 71) resulted in an increase in the phenolic content in the infested plants leaf sheath. The percentage increase in phenols in resistant and moderately resistant genotypes ranged from 14.8 % to 67.7 %. Upon infestation of BPH there was a decrease in total reducing sugars in all the resistant and moderately resistant genotypes. The highest quantity of reducing sugars was present in healthy susceptible check TN1 compared to all the resistant and moderately resistant backcross derived rice genotypes. The ascorbic acid content in the resistant and moderately resistant genotypes decreased after BPH infestation and percentage decrease ranged from 16% to 36%. The total N content in the infested resistant and moderately resistant genotypes decreased over healthy genotypes. Decrease in the N content was highest in the susceptible check TN1 (35.2%). In the resistant checks slight decrease in the N content was observed. Potassium and Phosphorous (%) increased in the resistant genotypes and resistant checks, but not in susceptible check TN1. The plants responded defensively upon infestation, resulting in production of higher amount of phenolics, potassium, phosphorous and reduced level of nitrogen, reducing sugars and ascorbic acid.
Integrative Approaches in Sericulture from Traditional Practices to Modern Technologies Sericulture and Its Contribution to Biodiversity Conservation
Authors: Attri Kapil , Vakayil Sreejith , G H Shruthi , Parmar Shradha , Harika Kama Ramya , Teja Katta Subramanya Sai , Panigrahi Chandan Kumar , P Jeevitha , R Kishan Kumar
Published: July 2024

This paper delves into the evolution of sericulture, tracing its transformation from traditional practices deeply rooted in cultural heritage to the adoption of modern technologies. Sericulture, the rearing of silkworms for silk production, has been a cornerstone of human civilization for millennia, contributing economically, culturally, and ecologically. The transition from traditional methods to advanced techniques has reshaped silk production, enhanced efficiency and quality while raising concerns about ecological sustainability. Traditional sericulture, characterized by organic farming and agroforestry, has played a crucial role in biodiversity conservation by promoting diverse ecosystems. Modern advancements, such as automated rearing systems and genetic engineering, have revolutionized the industry but also pose potential threats to ecological balance. This paper underscores the necessity of integrative approaches that combine traditional wisdom with modern innovations to ensure the future viability of sericulture. Such approaches foster interdisciplinary collaboration among scientists, farmers, policymakers, and industry stakeholders, aiming to develop sustainable strategies that prioritize environmental conservation, socio-economic development, and cultural heritage preservation. The paper calls for concerted efforts from all stakeholders, including policymakers, industry leaders, and consumers, to support sustainable practices in sericulture. By adopting holistic management practices and embracing diversity in perspectives, sericulture can emerge as a resilient agroecosystem capable of thriving amid the challenges of a rapidly changing world. This study ultimately highlights sericulture's potential as a model for sustainable development and environmental stewardship, advocating for practices that harmonize human ingenuity with nature's integrity.
Impact of Different Plant Densities and Fertilizer Levels on Yield Attributes, Yield and Fibre Quality Characters of Bt Cotton in HDPS
Authors: G Hemalatha , U Nagabhushanam , G. Veeranna , Ch Ramulu.
Published: July 2024

Adopting a high-density planting system in cotton cultivation has resulted in increased yields compared to traditional methods. Despite the clear benefits, farmers face various challenges throughout the cultivation process, from sowing to harvesting. However, selecting appropriate plant spacings, fertilizer levels and implementing tailored cultivation techniques can significantly enhance productivity. A field experiment was conducted at Siddapur research farm, Regional Agricultural Research Station, Warangal, Telangana, India during kharif 2023 to investigate the “Impact of different plant densities and fertilizer levels on yield attributes, yield and fibre quality characters of cotton in high density planting system (HDPS)”. The experiment was laid out in randomized block design (factorial) and replicated thrice, consisting of 12 treatment combinations comprising of three plant spacings S1: 80 x 20 cm (62,500 plants ha-1), S2: 90 x 15 cm (74,074 plants ha-1), S3: 90 x 60 cm in factor I and four fertilizer levels (F1: 100%RDF, F2: 125%RDF, F3: 100%RDF + Microbial consortia, F4: Control) in factor II. Both the factors significantly influenced the number of bolls per plant, number of bolls m-2 and seed cotton yield per hectare. The results revealed that higher no. of bolls plant-1 were recorded in 90 x 60 cm (18,518 plants ha-1) however, higher no. of bolls m-2, seed cotton yield (2233 kgha-1) obtained from higher plant density (74,074 plants ha-1) with the spacing 90 x 15 cm. Boll weight was not significantly influenced by varied plant spacings and fertilizer levels. Among the different levels of fertilizer, 125%RDF recorded highest no. of bolls per plant, no. of bolls m-2 and seed cotton yield (2362 kgha-1). Fibre quality characters viz., Upper half mean length(mm), micronaire(µginch-1), tenacity(gtex-1) and uniformity index (%) were not significantly influenced by both plant spacings and fertilizer levels as they are primarily governed by genetic makeup of cotton genotypes. For optimum seed cotton yield, cotton should be sown at closer spacing 90 x 15 cm and the application of 125%RDF was economically feasible in high density planting system.
Analysis of the Effects of Partially Hydrolyzed Polyamide on Oil Reservoir Rocks
Authors: Helstern Mihaela , Stoianovici Doru , Chis Timur
Published: July 2024

The exploitation of heavy oil fields has recently gained momentum due to increased investment in new oil and gas fields and especially due to environmental legislative constraints. That is why in this article I have described the possibility of using partially hydrolyzed polyacrylamide in the exploitation of heavy crude oil deposits, by injecting it into reservoir rocks followed by injection of reservoir water. The role of this polymer is to provide lubrication of the crude oil and water flow channels and especially to block (by reverse osmosis) the large pore communication channels in order to limit pressure leaks in uncontrollable areas. In the study we created two polymers that were used in order to increase the flow rate and decrease the viscosity and the freezing point (additives that are easy to procure and especially with spectacular results in the treatment of stills and without affecting the stability and quality of the final products refinery). We also studied the flow of the polymer through carbonate reservoir rocks, managing to obtain a numerical model that provides data on the rock resistance factor to the flow of partially fluidized polyacrylamide. The adsorption on the surface of the rocks determined the reduction of the mobility of the polymer but also the modification of the gel structure by the modification (crossing) of the polymer (of the polymer chains) which led to clogging (blocking of the pores) and increasing the possibility of fluid flow. In the laboratory we determined the adsorption of silicon for a solution of polyacrylamide of 0.05% partially hydrolyzed concentration in water, it increases from the value of 0.01 mg/m2 to 0.05 mg/m2 when the concentration in NaCl increases from 0 .5% to 10% in are we showed that adsorption increases for pH values ​​lower than 7, and it is stated that for a porous sand medium with a permeability of 140 mD, replacing saline water with 20 g/l NaCl, a presence of the polymer with a concentration of 400 ppm was observed in the effluent, and this value being approximately stabilized after 5 injected pore volumes.
Spacing Simultaneously Promotes Multiple Forms of Learning in Children's Science Curriculum
Authors: Gluckman Maxie , Vlach Haley A. , Sandhofer Catherine M.
Published: January 2014

Thespacing effect refers to the robust finding that long‐term memory is promoted when learning events are distributed in time rather than massed in immediate succession. The current study extended research on the spacing effect by examining whether spaced learning schedules can simultaneously promote multiple forms of learning, such as memory and generalization, in the context of an educational intervention. Thirty‐six early elementary school‐aged children were presented with science lessons on one of three schedules: massed, clumped, and spaced. At a 1‐week delayed test, children in the spaced condition demonstrated improvements in both memory and generalization, significantly outperforming children in the other conditions. However, there was no observed relationship between children's memory performance and generalization performance. The current study highlights directions for future research and contributes to a growing body of work demonstrating the benefits of spaced learning for educational curriculum. Copyright © 2014 John Wiley & Sons, Ltd.
Asymmetric Michael Addition of Oxindoles to Allenoate Catalyzed by N‐Acyl Aminophosphine: Construction of Functionalized Oxindoles with Quaternary Stereogenic Center
Authors: Chen Jinhao , Cai Yuepeng , Zhao Gang
Published: January 2014

A novel reaction between ethyl allenoate and oxindoles that enables the asymmetric synthesis of 3,3‐bisubstituted oxindoles with our previously established bifunctional N‐acyl aminophosphine catalysts is reported. These products bearing a chiral quaternary carbon center at the C‐3 position of the oxindoles may have potential significance in the synthesis of related structures. The best performance of these processes provides adducts with 92% yield and 94% ee.

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Structural Determinants for the Non‐Canonical Substrate Specificity of the ω‐Transaminase from Paracoccus denitrificans
Authors: Park Eul‐Soo , Park Sae‐Rom , Han Sang‐Woo , Dong Joo‐Young , Shin Jong‐Shik
Published: January 2014

Substrate binding pockets of ω‐transaminase (ω‐TA) consist of a large (L) pocket capable of dual recognition of hydrophobic and carboxyl substituents, and a small (S) pocket displaying a strict steric constraint that permits entry of a substituent no larger than an ethyl group. Despite the unique catalytic utility of ω‐TA enabling asymmetric reductive amination of carbonyl compounds, the severe size exclusion occurring in the S pocket has limited synthetic applications of ω‐TA to access structurally diverse chiral amines and amino acids. Here we report the first example of an ω‐TA whose S pocket shows a non‐canonical steric constraint and readily accommodates up to an n‐butyl substituent. The relaxed substrate specificity of the (S)‐selective ω‐TA, cloned from Paracoccus denitrificans (PDTA), afforded efficient asymmetric syntheses of unnatural amino acids carrying long alkyl side chains such as L‐norvaline and L‐norleucine. Molecular modeling using the recently released X‐ray structure of PDTA could pinpoint an exact location of the S pocket which had remained dubious. Entry of a hydrophobic substituent in the L pocket was found to have the S pocket accept up to an ethyl substituent, reminiscent of the canonical steric constraint. In contrast, binding of a carboxyl group to the L pocket induced a slight movement of V153 away from the small‐pocket‐forming residues. The resulting structural change elicited excavation of the S pocket, leading to formation of a narrow tunnel‐like structure allowing accommodation of linear alkyl groups of carboxylate‐bearing substrates. To verify the active site model, we introduced site‐directed mutagenesis to six active site residues and examined whether the point mutations alleviated the steric constraint in the S pocket. Consistent with the molecular modeling results, the V153A variant assumed an elongated S pocket and accepted even an n‐hexyl substituent. Our findings provide precise structural information on substrate binding to the active site of ω‐TA, which is expected to benefit rational redesign of substrate specificity of ω‐TA.

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Novel Risk Loci for Rheumatoid Arthritis in Han Chinese and Congruence With Risk Variants in Europeans
Authors: Jiang Lei , Yin Jian , Ye Lingying , Yang Jian , Hemani Gibran , Liu Ai‐jun , Zou Hejian , He Dongyi , Sun Lingyun , Zeng Xiaofeng , Li Zhanguo , Zheng Yi , Lin Yiping , Liu Yi , Fang Yongfei , Xu Jianhua , Li Yinong , Dai Shengming , Guan Jianlong , Jiang Lindi , Wei Qianghua , Wang Yi , Li Yang , Huang Cibo , Zuo Xiaoxia , Liu Yu , Wu Xin , Zhang Libin , Zhou Ling , Zhang Qing , Li Ting , Chen Ling , Xu Zhen , Yang Xiaoping , Qian Feng , Xie Weilin , Liu Wei , Guo Qian , Huang Shaolan , Zhao Jing , Li Mengmeng , Jin Yanhua , Gao Jie , Lv Ying , Wang Yiwen , Lin Li , Guo Aihua , Danoy Patrick , Willner Dana , Cremin Catherine , Hadler Johanna , Zhang Fengchun , Zhao Yan , Li Mengtao , Yue Tao , Fan Xiaolei , Guo Jianping , Mu Rong , Li Jingyi , Wu Chao , Zeng Ming , Wang Jiucun , Li Shilin , Jin Li , Wang Binbin , Wang Jing , Ma Xu , Sun Liangdan , Zhang Xuejun , Brown Matthew A. , Visscher Peter M. , Su Ding‐feng , Xu Huji
Published: January 2014

Objective

To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans.

Methods

A genome‐wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta‐analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations.

Results

Three non–major histocompatibility complex (non‐MHC) loci were identified at the genome‐wide significance level, the effect sizes of which were larger in anti–citrullinated protein antibody (ACPA)–positive patients than in ACPA‐negative patients. These included 2 novel variants, rs12617656, located in an intron of DPP4 (odds ratio [OR] 1.56, P = 1.6 × 10−21), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 × 10−16), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 × 10−15). The analysis of ACPA‐positive patients versus ACPA‐negative patients revealed that rs12617656 at the DPP4 locus showed a strong interaction effect with ACPAs (P = 5.3 × 10−18), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 × 10−8). The transpopulation meta‐analysis showed genome‐wide overlap and enrichment in association signals across the 2 populations, as confirmed by prediction analysis.

Conclusion

This study has expanded the list of alleles that confer risk of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants.
Organocatalyzed Highly Diastereo‐ and Enantioselective Tandem Sulfa‐Michael–Mannich Reaction of 2‐Mercaptoquinoline‐3‐carbaldimines with Maleimides
Authors: Wu Lulu , Wang Youming , Song Haibin , Tang Liangfu , Zhou Zhenghong , Tang Chuchi
Published: January 2014

A highly diastereo‐ and enantioselective organocatalyzed domino sulfa‐Michael–Mannich reaction of 2‐mercaptoquinoline‐3‐carbaldimines with maleimides has been developed. This approach provides a convenient and efficient access to multifuntionalized tetracyclic quinoline derivatives with three contiguous stereocenters in high yield with excellent stereoselectivity (up to >99:1 dr and >99 % ee).
Design, Synthesis, and Biological Activity of NCC149 Derivatives as Histone Deacetylase 8‐Selective Inhibitors
Authors: Suzuki Takayoshi , Muto Nobusuke , Bando Masashige , Itoh Yukihiro , Masaki Ayako , Ri Masaki , Ota Yosuke , Nakagawa Hidehiko , Iida Shinsuke , Shirahige Katsuhiko , Miyata Naoki
Published: January 2014

We recently discovered N‐hydroxy‐3‐[1‐(phenylthio)methyl‐1H‐1,2,3‐triazol‐4‐yl]benzamide (NCC149) as a potent and selective histone deacetylase 8 (HDAC8) inhibitor from a 151‐member triazole compound library using a click chemistry approach. In this work, we present a series of NCC149 derivatives bearing various aromatic linkers that were designed and synthesized as HDAC8‐selective inhibitors. A series of in vitro assays were used to evaluate the newly synthesized compounds, four of which showed HDAC8 inhibitory activity similar to that of NCC149, and one of which displayed HDAC8 selectivity superior to that of NCC149. In addition, these top four compounds induced the increase of acetylated cohesin (an HDAC8 substrate) in HeLa cells in a dose‐dependent manner, indicating inhibition of HDAC8 in the cells. While none of these compounds enhanced the acetylation of H3K9 (a substrate of HDAC1 and 2), only one compound refrained from increasing α‐tubulin acetylation, a substrate of HDAC6, indicating that this compound is more selective for HDAC8 than the other derivatives. Furthermore, this HDAC8‐selective inhibitor suppressed the growth of T‐cell lymphoma cells more potently than did NCC149. These findings are useful for the further development of HDAC8‐selective inhibitors.
An Integrated Experimental and Theoretical Approach to the Spectroscopy of Organic‐Dye‐Sensitized TiO2 Heterointerfaces: Disentangling the Effects of Aggregation, Solvation, and Surface Protonation
Authors: Marotta Gabriele , Lobello Maria Grazia , Anselmi Chiara , Barozzino Consiglio Gabriella , Calamante Massimo , Mordini Alessandro , Pastore Mariachiara , De Angelis Filippo
Published: January 2014

We report a joint experimental and computational study into the spectroscopic properties of a prototypical D5 organic dye, both in solution and adsorbed on a TiO2 surface, with the aim of modeling and quantifying the UV/Vis spectral shifts that occur in the different explored environments. Going from the dye in solution to dye‐sensitized TiO2, various factors may shift the position of the UV/Vis absorption maximum, both towards longer and shorter wavelengths. Here we have focused on the effect of dye aggregation on TiO2, surface protonation, and solvent effects. The D5 dye forms stable aggregates on the TiO2 surface that cause spectral blueshifts. We used different sensitization conditions to vary the dye loading and thus the extent of dye aggregation. For each sensitization condition, we explored protonated and native TiO2 films. Computational modeling of different dimeric aggregates with increasing intermolecular interactions and simulation of the associated optical responses also confirm the observed spectral blueshifts. Our results show that both the presence of surface protons and solvent stabilize the excited state of the adsorbed dye molecules, which causes a marked redshift in the absorption maximum and thus moves in the opposite direction to the shift due to the increase in the surface coverage.
The Synthetic Challenge of Thioglycolurils
Authors: Singh Mandeep , Parvari Galit , Botoshansky Mark , Keinan Ehud , Reany Ofer
Published: January 2014

The very high stability of cucurbiturils under harsh acidic conditions and their reported prolific chemistry over more than three decades pose a question: why has no thiocucurbituril been reported to date? Furthermore, although glycoluril is a highly stable, easily accessible precursor of all cucurbiturils, its sulfur analog represents a yet unmet synthetic challenge. The reaction between glyoxal and thiourea was found to stop at the level of dihydroxyimidazolidine‐2‐thione, which is quite unstable under various acidic conditions. In an attempt to answer these questions, several stable analogs of thioglycoluril, that is, monothioglycoluril, ditolylthioglycoluril, and its diether derivative were prepared and characterized in the hope that they could be employed as building blocks for the synthesis of thiocucurbiturils. Several side products were also obtained that highlight the complex reactivity of thiourea in these reactions. The crystal structures of the above‐mentioned thioglycolurils are dominated by networks of hydrogen‐bonding interactions. Attempts to co‐oligomerize these compounds with formaldehyde clearly suggest that it is impossible to synthesize thiocucurbiturils by the methods commonly used for the preparation of cucurbiturils. Given that thiocucurbiturils are expected to be stable molecules, alternative synthetic strategies that are different from the thermodynamically controlled approaches must be designed.
Advanced Bayesian Estimation of Weibull Early Life Failure Distributions
Authors: Kurz Daniel , Lewitschnig Horst , Pilz Jürgen
Published: January 2014

In semiconductor manufacturing, it is a key to ensure reliability of the produced devices. The population's reliability level is demonstrated by means of a burn‐in study (that is investigating a large number of devices under real‐life stress conditions for product relevant fails). Burn‐in settings are based on the lifetime distribution of early fails. Typically, it is modelled as a Weibull distribution Wb(a,b) with scale parameter a > 0 and shape parameter b ∈ (0,1) motivated by a decreasing failure rate within the devices' early life. Depending on the applied burn‐in scheme, the Weibull parameters have to be estimated from time‐to‐failure and discrete failure count data, respectively. In this paper, we present advanced Bayesian estimation models for the Weibull distribution handling both data situations. First, a simplified conjugate approach using gamma‐histogram‐beta priors is presented. Further, according to the paper's main focus, an extended Bayesian concept for assessing Weibull early life failure distributions is highlighted. It is characterized by a Dirichlet prior distribution applied to the lifetime function of early fails. The proposed model simplifies the incorporation of engineering prior knowledge. Moreover, it can be extended to both discrete failure and time‐to‐failure burn‐in data. The joint posterior distribution, Bayesian estimators and compounded and joint credible regions are derived by means of Monte Carlo simulation. The principle of Bayesian learning allows to update the Weibull early life failure distribution whenever new failure data become available. Therefore, burn‐in settings can dynamically be adapted improving the efficiency of burn‐in. Copyright © 2014 John Wiley & Sons, Ltd.
The steady‐state behavior of the synthetic and side‐sensitive synthetic double sampling charts
Authors: Costa Antonio Fernando Branco , Machado Marcela Aparecida Guerreiro
Published: January 2014

The steady‐state average run length is used to measure the performance of the recently proposed synthetic double sampling chart (synthetic DS chart). The overall performance of the DS chart in signaling process mean shifts of different magnitudes does not improve when it is integrated with the conforming run length chart, except when the integrated charts are designed to offer very high protection against false alarms, and the use of large samples is prohibitive. The synthetic chart signals when a second point falls beyond the control limits, no matter whether one of them falls above the centerline and the other falls below it; with the side‐sensitive feature, the synthetic chart does not signal when they fall on opposite sides of the centerline. We also investigated the steady‐state average run length of the side‐sensitive synthetic DS chart. With the side‐sensitive feature, the overall performance of the synthetic DS chart improves, but not enough to outperform the non‐synthetic DS chart. Copyright © 2014 John Wiley & Sons, Ltd.
Assessment of Mutational Load in Biopsy Tissue Provides Additional Information About Genomic Instability to Histological Classifications of Barrett's Esophagus
Authors: Khara Harshit S. , Jackson Sara A. , Nair Saraswathi , Deftereos Georgios , Patel Shweta , Silverman Jan F. , Ellsworth Eric , Sumner Cameron , Corcoran Brendan , Smith Dennis M. , Finkelstein Sydney , Gross Seth A.
Published: January 2014

Purpose

Progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is associated with accumulated genomic instability. Current risk stratification of BE for EAC relies on histological classification and grade of dysplasia. However, histology alone cannot assess the risk of patients with inconsistent or non-dysplastic BE histology. We, therefore, examined the presence and extent of genomic instability in advanced and less advanced BE histology using mutational load (ML).

Methods

ML summarized the presence and clonality of loss of heterozygosity (LOH) mutations and the emergence of new alleles, manifested as microsatellite instability (MSI) mutations, in ten genomic loci around tumor suppressor genes associated with EAC. The ML of 877 microdissected targets from BE biopsies was correlated to their histology. Histological targets were categorized into three levels: no ML, low ML, and high ML.

Results

Increasing ML correlated with increasingly severe histology. By contrast, proportions of targets that lacked mutations decreased with increasingly severe histology. A portion of targets with non-dysplastic and low-grade histology shared a similar ML as those with higher risk and EAC disease. The addition of MSI characterization to ML helped to differentiate the ML between advanced and less advanced histology.

Conclusions

Given that EAC is associated with accumulated genomic instability, high ML in less severe histology may identify BE disease at greater risk of progression to EAC. ML may help to better manage BE in early histological stages and when histology alone provides insufficient information.
Coupling of the Okuda–Dawson model with a shear current-driven wave and the associated instability
Authors: MASOOD W. , SALEEM H.
Published: January 2014

It is pointed out that the Okuda–Dawson mode can couple with the newly proposed current-driven wave. It is also shown that the Shukla–Varma mode can couple with these waves if the density inhomogeneity is taken into account in a plasma containing stationary dust particles. A comparison of several low-frequency electrostatic waves and instabilities driven by shear current and shear plasma flow in an electron–ion plasma with and without stationary dust is also presented.
Emerging paradigms in anti-infective drug design
Authors: BARRETT MICHAEL P. , CROFT SIMON L.
Published: January 2014

The need for new drugs to treat microbial infections is pressing. The great progress made in the middle part of the twentieth Century was followed by a period of relative inactivity as the medical needs relating to infectious disease in the wealthier nations receded. Growing realisation that anti-infectives are needed in many parts of the world, to treat neglected diseases as well as to combat the burgeoning risk of resistance to existing drugs, has galvanised a new wave of research into anti-microbial drugs. The transfer of knowledge from the Pharmaceutical industry relating to the importance of understanding how to target drugs successfully within the body, and improved understanding of how pathogens interact with their hosts, is driving a series of new paradigms in anti-infective drug design. Here we provide an overview of those processes as an introduction to a series of articles from experts in this area that emerged from a meeting entitled “Emerging Paradigms in Anti-Infective Drug Design” held in London on the 17th and 18th September 2012. The symposium was organised jointly by British Society for Parasitology (BSP) and the Biological & Medicinal Chemistry sector of the Royal Society of Chemistry (RSC) and held at the London School of Hygiene & Tropical Medicine. The symposium set out to cover all aspects of the identification of new therapeutic modalities for the treatment of neglected and tropical diseases. We aimed to bring together leading scientists from all the disciplines working in this field and cover the pharmacology, medicinal chemistry and drug delivery of potential new medicines. Sessions were held on: “Target diseases and targets for drugs”, “Target based medicinal chemistry”, “Bioavailability and chemistry”, “Targeting intracellular microbes”, “Alternative approaches and models”, and “New anti-infectives – how do we get there?”

This symposium was organised by Simon Croft (LSHTM) and Mike Barrett (University of Glasgow) for the BSP, and David Alker (David Alker Associates) and Andrew Stachulski (University of Liverpool) for the Biological & Medicinal Chemistry sector of the RSC.