bluuebunny/crossref_metadata_2025 huggingface dataset:
Morean aspects of Erasmus’ Vita Hieronymi
Authors: Murphy Clare M.
Published: January 2017

Erasmus was a biographer not only of Jerome but, through four of his letters, of More also. The subject of ancestry is treated similarly by Erasmus writing of Jerome and by More writing of Pico. Erasmus stresses the training in rhetoric and letters, in languages, scriptural study, and patristics of both Jerome and More. The author explores the identification of writers with their subject, and then focuses on similar attitudes of Jerome, Erasmus, and More regarding the education of women and the dangers of heresy.
University of Oxford, 12th July 1987
Authors: Platt John
Published: January 2017

Dr Platt begins by examining the reformist credentials of More that he shared with other humanists, particularly Colet and Erasmus. The humanist desire to draw from the fountain-source is explored and the need for Greek scholarship is identified as a key factor in scriptural interpretation. Finally, Dr. Platt investigates the dilemmas the humanists faced as the Protestant Reformation began to emerge in early 16th century Europe.
Bishop of Birmingham, 23rd July 1989
Authors: Santer Mark
Published: January 2017

In this paper, Bishop Santer explores the issue of authority, which haunted English and European Church history in the early 16th century. The constant stresses between local, national and international interests frequently informed the rise of conflict, when these various interests were in tension. He goes on to discuss the difficulties that national Churches have experienced in subsequent history. Thomas More’s principles sought to provide an answer to the statement of the Nicene Creed “I believe in the Catholic Church”. Drawing from his experience on the Anglican Roman Catholic International Commission, Bishop Santer considers that the questions posed by More are unavoidable in the quest for Church unity.
Vicar of Chelsea Old Church, 1950-1992, July 9th, 1995
Authors: Thomson Leighton
Published: January 2017

In this paper, Leighton Thomson provides the reader with an overview of early 16th century English history and he explores the achievements and reversals of the period in terms of the epoch of discovery, the Renaissance humanists and the first stirrings of the Reformation. A contrast is drawn between Thomas More and his contemporary reformers, particularly William Tyndale and Martin Luther.
Director of Moreanum. 15th July 1979
Authors: Marc’hadour Germain
Published: January 2017

This address responds in some detail to the place and to the date of its delivery. It was on July 15th (1896) that Chelsea acquired the German statuette of More, which was unveiled in the Public Library on the 23rd: the then Vicar of Chelsea Old Church was one of the contributors to the purchase. Thomas More, a model parishioner, loved that church, embellished it, treated it as the heart of his family’s prayer life, and took an active part in its liturgies. He had his first wife’s mortal remains buried there and his own epitaph carved above her tomb. He often dated events by the Christian calendar . If he wished to die on July 6th, it was to unite his martyrdom with those of St Peter and St Thomas Becket. The month of July is exceptionally rich in Morean anniversaries: from the day of More’s trial on the 1st, the beautiful prayer he penned between his condemnation and his execution, the marriage of his beloved daughter, Margaret, on the 2nd. July 6th saw the accession of Queen Mary Tudor, which made it possible to publish the prison writings of More, and it saw the death in exile of Margaret Giggs, More’s adopted daughter. Erasmus, who died on July 12th, had been his first biographer through an open letter signed July 23rd (1519). It was in July that More assumed, and later resigned, the office of Undersheriff. In July the Chelsea Old Church was rededicated and the statue, bought by public subscription, was inaugurated on the Chelsea Embankment. More’s own voice joins our service through quotations from the prayer he composed in July 1535.
Omori’s law: a note on the history of geophysics
Authors: Guglielmi A V
Published: January 2017

In the late nineteenth century, the Japanese seismologist Omori discovered the first law of earthquake physics, which states that the rate of aftershocks decreases hyperbolically with time. Over the years since then, there has been a vast amount of literature on this law, and the significance of its discovery has been universally recognized. There is, however, a profound division of opinion as to the interpretation of the law. Some argue that Omori just proposed a simple data-fitting formula and replace this formula by a power-law one with a negative fractional exponent, whereas for others the Omori law makes physical sense. The paper describes the history and essence of Omori’s discovery, with special attention paid to interpretational questions. It is shown that Omori’s original formulation of the law correlates well with the current understanding of the rock destruction mechanism at the earthquake focus.
Negative ion adsorption by the ion source surface as a factor influencing ion lifetime measurements
Authors: Lukin V G , Khvostenko O G
Published: January 2017

It is well known that negative ions formed in the gas phase through low-energy electron capture by molecules show a scatter in the measured lifetimes of their autodetachment states. In considering this question, it was found that, when using a static sector magnetic mass spectrometer, some of the ions formed on the ionization chamber walls are adsorbed and stabilized there, then joining the registered ion flux and thereby distorting their measured lifetime. Because the number of the adsorbed ions depends on the experimental conditions, their contribution to the total flux is to some extent uncontrollable—hence, the scatter.
Electrohydrodynamic flow for the active control of gas flows
Authors: Khomich V Yu , Yamshchikov V A
Published: January 2017

A new approach to producing powerful electrohydrodynamic flows in a gas environment is discussed, in which a barrier discharge distributed over a dielectric surface is used as an intense ion source. Electric discharge systems for active control of gas flows with a high (> 15 l s−1) volumetric rate are developed and investigated. A highly effective multidischarge actuator system is created to control air flows over aerodynamic surfaces with a significantly higher actuator force and energy characteristics than those in known global analogs.
Acknowledgement to Reviewers of Antibodies in 2016
Authors:   Antibodies Editorial Office
Published: January 2017

The editors of Antibodies would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...]
Enhanced Iron and Selenium Uptake in Plants by Volatile Emissions of Bacillus amyloliquefaciens (BF06)
Authors: Wang Jianfei , Zhou Cheng , Xiao Xin , Xie Yue , Zhu Lin , Ma Zhongyou
Published: January 2017

Volatile organic compounds (VOCs) released by plant growth-promoting rhizobacteria (PGPR) are involved in promoting growth and triggering systemic resistance (ISR) in plants. Importantly, the release of VOCs by some PGPR strains confers improved plant uptake of nutrient elements from the soil. However, the underlying mechanisms of VOCs-regulated nutrient acquisition remain elusive. In this study, VOCs were extracted and identified from Bacillus amyloliquefaciens (strain BF06) using gas chromatography–mass spectrometry (GC–MS). BF06 VOCs exposure significantly promoted the growth and photosynthesis of Arabidopsis plants. To explore how microbial VOCs stimulate growth in plants, gene expression profiles of Arabidopsis seedlings exposed to BF06 VOCs were examined using transcriptomic analyses. In screening differentially expressed genes (DEGs), most upregulated DEGs were found to be related to amino acid transport, iron (Fe) uptake and homeostasis, and sulfate transport. Furthermore, BF06 VOCs significantly enhanced Fe absorption in plants under Fe-limited conditions. However, when nitric oxide (NO) synthesis was inhibited, BF06 VOCs exposure could not substantially augment Fe acquisition in plants under alkaline stress, indicating that VOCs-mediated plant uptake of Fe was required for induction of root NO accumulation. In addition, BF06 VOCs exposure led to a marked increase in some genes encoding for sulfate transporters, and further increased Se accumulation in plants. Intriguingly, BF06 VOCs exposure failed to increase Se uptake in sultr1;2 mutants, which may indicate that high-level transcription of these sulfate transporters induced by BF06 VOCs was essential for enhancing Se absorption by plants. Taken together, our results demonstrated the potential of VOCs released by this strain BF06 to increase Fe and Se uptake in plants.
Numerical Modelling of the Czochralski Growth of β-Ga2O3
Authors: Miller Wolfram , Böttcher Klaus , Galazka Zbigniew , Schreuer Jürgen
Published: January 2017

Our numerical modelling of the Czochralski growth of single crystalline β-Ga 2 O 3 crystals (monoclinic symmetry) starts at the 2D heat transport analysis within the crystal growth furnace, proceeds with the 3D heat transport and fluid flow analysis in the crystal-melt-crucible arrangement and targets the 3D thermal stress analysis within the β-Ga 2 O 3 crystal. In order to perform the stress analysis, we measured the thermal expansion coefficients and the elastic stiffness coefficients in two samples of a β-Ga 2 O 3 crystal grown at IKZ. Additionally, we analyse published data of β-Ga 2 O 3 material properties and use data from literature for comparative calculations. The computations were performed by the software packages CrysMAS, CGsim, Ansys-cfx and comsol Multiphysics. By the hand of two different thermal expansion data sets and two different crystal orientations, we analyse the elastic stresses in terms of the von-Mises stress.
A Promising Future for Prostate Cancer Diagnostics
Authors: Assinder Stephen , Bhoopalan Vanitha
Published: January 2017

It has been estimated that globally there is a death attributable to prostate cancer every four minutes. As life expectancy in all world regions increases, so too incidence of this disease of the ageing male will increase. For many men diagnosis occurs after presentation with symptoms of altered urinary dynamics. Unfortunately, these changes, whilst also associated with benign disease, are evident quite late in the aetiology of prostate cancer. Early detection provides for better management and prognosis. This Special Issue provides an up to date view of the advances made towards early diagnosis and prognosis. It provides reviews of advanced imaging techniques (e.g., multiparametric MRI and protocols), and of biomaterials and molecular biomarkers currently being explored (e.g., microRNAs, proteomics) and the technologies that are revolutionizing this field. It describes the multi-disciplinary approaches that are essential to inexpensive, deliverable and accurate platforms for prostate cancer diagnostics.
A Probabilistic Damage Identification Method for Shear Structure Components Based on Cross-Entropy Optimizations
Authors: Guan Xuefei , Wang Yongxiang , He Jingjing
Published: January 2017

A probabilistic damage identification method for shear structure components is presented. The method uses the extracted modal frequencies from the measured dynamical responses in conjunction with a representative finite element model. The damage of each component is modeled using a stiffness multiplier in the finite element model. By coupling the extracted features and the probabilistic structural model, the damage identification problem is recast to an equivalent optimization problem, which is iteratively solved using the cross-entropy optimization technique. An application example is used to demonstrate the proposed method and validate its effectiveness. Influencing factors such as the location of damaged components, measurement location, measurement noise level, and damage severity are studied. The detection reliability under different measurement noise levels is also discussed in detail.
Efficient Energy Consumption Scheduling: Towards Effective Load Leveling
Authors: Hong Yuan , Wang Shengbin , Huang Ziyue
Published: January 2017

Different agents in the smart grid infrastructure (e.g., households, buildings, communities) consume energy with their own appliances, which may have adjustable usage schedules over a day, a month, a season or even a year. One of the major objectives of the smart grid is to flatten the demand load of numerous agents (viz. consumers), such that the peak load can be avoided and power supply can feed the demand load at anytime on the grid. To this end, we propose two Energy Consumption Scheduling (ECS) problems for the appliances held by different agents at the demand side to effectively facilitate load leveling. Specifically, we mathematically model the ECS problems as Mixed-Integer Programming (MIP) problems using the data collected from different agents (e.g., their appliances’ energy consumption in every time slot and the total number of required in-use time slots, specific preferences of the in-use time slots for their appliances). Furthermore, we propose a novel algorithm to efficiently and effectively solve the ECS problems with large-scale inputs (which are NP-hard). The experimental results demonstrate that our approach is significantly more efficient than standard benchmarks, such as CPLEX, while guaranteeing near-optimal outputs.
Power Quality Disturbance Classification Using the S-Transform and Probabilistic Neural Network
Authors: Wang Huihui , Wang Ping , Liu Tao
Published: January 2017

This paper presents a transient power quality (PQ) disturbance classification approach based on a generalized S-transform and probabilistic neural network (PNN). Specifically, the width factor used in the generalized S-transform is feature oriented. Depending on the specific feature to be extracted from the S-transform amplitude matrix, a favorable value is determined for the width factor, with which the S-transform is performed and the corresponding feature is extracted. Four features obtained this way are used as the inputs of a PNN trained for performing the classification of 8 disturbance signals and one normal sinusoidal signal. The key work of this research includes studying the influence of the width factor on the S-transform results, investigating the impacts of the width factor on the distribution behavior of features selected for disturbance classification, determining the favorable value for the width factor by evaluating the classification accuracy of PNN. Simulation results tell that the proposed approach significantly enhances the separation of the disturbance signals, improves the accuracy and generalization ability of the PNN, and exhibits the robustness of the PNN against noises. The proposed algorithm also shows good performance in comparison with other reported studies.
A Lyapunov Stability Theory-Based Control Strategy for Three-Level Shunt Active Power Filter
Authors: Cao Yijia , Xu Yong , Li Yong , Yu Jiaqi , Yu Jingrong
Published: January 2017

The three-phase three-wire neutral-point-clamped shunt active power filter (NPC-SAPF), which most adopts classical closed-loop feedback control methods such as proportional-integral (PI), proportional-resonant (PR) and repetitive control, can only output 1st–25th harmonic currents with 10–20 kHz switching frequency. The reason for this is that the controller design must make a compromise between system stability and harmonic current compensation ability under the condition of less than 20 kHz switching frequency. To broaden the bandwidth of the compensation current, a Lyapunov stability theory-based control strategy is presented in this paper for NPC-SAPF. The proposed control law is obtained by constructing the switching function on the basis of the mathematical model and the Lyapunov candidate function, which can avoid introducing closed-loop feedback control and keep the system globally asymptotically stable. By means of the proposed method, the NPC-SAPF has compensation ability for the 1st–50th harmonic currents, the total harmonic distortion (THD) and each harmonic content of grid currents satisfy the requirements of IEEE Standard 519-2014. In order to verify the superiority of the proposed control strategy, stability conditions of the proposed strategy and the representative PR controllers are compared. The simulation results in MATLAB/Simulink (MathWorks, Natick, MA, USA) and the experimental results obtained on a 6.6 kVA NPC-SAPF laboratory prototype validate the proposed control strategy.
Fire Hazards of Some Modern Solid Fuels
Authors: Novozhilov Vasily
Published: January 2017

Fire hazard during ship transportation of certain modern solid fuels is identified. A particular mechanism which may lead to catastrophic ship fire is discussed. A mathematical model predicting time to such fully developed fire (flashover time) I s proposed. An analytical solution is obtained for the developed model. An important part of this solution is a closed form analytical description of the smoke filling dynamics in a closed compartment. It is demonstrated that flashover time depends on a number of parameters. The relative importance of these parameters is discussed. Particular significance is attributed to fuel soot propensity (fuel soot yield) which is an intrinsic fuel property. This parameter controls the intensity of radiative heat exchange in the compartment, and its influence on flashover time is of paramount importance. It is suggested that fuels are ranked with respect to this parameter in order to describe their relative fire hazards. This ranking should be implemented into the regulatory framework governing fuel transportation by ships.
Challenges of Dementia Care in China
Authors: Chen Zheng , Yang Xuan , Song Yuetao , Song Binbin , Zhang Yi , Liu Jiawen , Wang Qing , Yu Jia
Published: January 2017

Dementia results in brain dysfunction, disability and dependency among affected people, causing an overwhelming burden for caregivers. China has the largest number of people with dementia worldwide and is facing severe challenges with respect to dementia care, including poor awareness of dementia in the public, inadequate knowledge of dementia for medical professionals and caregivers, an underdeveloped dementia service system, and high costs of dementia care. To address these challenges, China is taking action to increase dementia awareness and education among the public and care providers, and develop policies, services and resources for dementia care.
Transcriptome Profiling of the Lungs Reveals Molecular Clock Genes Expression Changes after Chronic Exposure to Ambient Air Particles
Authors: Song Pengcheng , Li Zhigang , Li Xiaoqian , Yang Lixin , Zhang Lulu , Li Nannan , Guo Chen , Lu Shuyu , Wei Yongjie
Published: January 2017

The symptoms of asthma, breathlessness, insomnia, etc. all have relevance to pulmonary rhythmic disturbances. Epidemiology and toxicology studies have demonstrated that exposure to ambient air particles can result in pulmonary dysfunction. However, there are no data directly supporting a link between air pollution and circadian rhythm disorder. In the present study, we found that breathing highly polluted air resulted in changes of the molecular clock genes expression in lung by transcriptome profiling analyses in a rodent model. Compared to those exposed to filtered air, in both pregnant and offspring rats in the unfiltered group, key clock genes (Per1, Per2, Per3, Rev-erbα and Dbp) expression level decreased and Bmal1 expression level increased. In both rat dams and their offspring, after continuous exposure to unfiltered air, we observed significant histologic evidence for both perivascular and peribronchial inflammation, increased tissue and systemic oxidative stress in the lungs. Our results suggest that chronic exposure to particulate matter can induce alterations of clock genes expression, which could be another important pathway for explaining the feedbacks of ambient particle exposure in addition to oxidative stress and inflammation.
A Thoroughly Validated Virtual Screening Strategy for Discovery of Novel HDAC3 Inhibitors
Authors: Hu Huabin , Xia Jie , Wang Dongmei , Wang Xiang , Wu Song
Published: January 2017

Histone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches. We have identified FRED (Chemgauss4) docking against a structural model of HDAC3, i.e., SAHA-3 generated by a computationally inexpensive “flexible docking”, as the best SBVS approach and a common feature pharmacophore model, i.e., Hypo1 generated by Catalyst/HipHop as the optimal model for LBVS. We then developed a pipeline that was composed of Hypo1, FRED (Chemgauss4), and SAHA-3 sequentially, and demonstrated that it was superior to other combinations in terms of ligand enrichment. In summary, we present the first highly-validated, rationally-designed VS strategy specific to HDAC3 inhibitor discovery. The constructed pipeline is publicly accessible for the scientific community to identify novel HDAC3 inhibitors in a time-efficient and cost-effective way.
Osteocalcin Mediates Biomineralization during Osteogenic Maturation in Human Mesenchymal Stromal Cells
Authors: Tsao Yu-Tzu , Huang Yi-Jeng , Wu Hao-Hsiang , Liu Yu-An , Liu Yi-Shiuan , Lee Oscar
Published: January 2017

There is a growing interest in cell therapies using mesenchymal stromal cells (MSCs) for repairing bone defects. MSCs have the ability to differentiate into osteoprogenitors and osteoblasts as well as to form calcified bone matrix. However, the molecular mechanisms governing mineralization during osteogenic differentiation remain unclear. Non-collagenous proteins in the extracellular matrix are believed to control different aspects of the mineralization. Since osteocalcin is the most abundant non-collagenous bone matrix protein, the purpose of this study is to investigate the roles of osteocalcin in mineral species production during osteogenesis of MSCs. Using Raman spectroscopy, we found that the maturation of mineral species was affected by osteocalcin expression level. After osteocalcin was knocked down, the mineral species maturation was delayed and total hydroxyapatite was lower than the control group. In addition, the expression of osteogenic marker genes, including RUNX2, alkaline phosphatase, type I collagen, and osteonectin, was downregulated during osteogenic differentiation compared to the control group; whereas gene expression of osterix was upregulated after the knockdown. Together, osteocalcin plays an essential role for the maturation of mineral species and modulates osteogenic differentiation of MSCs. The results offer new insights into the enhancement of new bone formation, such as for the treatments of osteoporosis and fracture healing.
Inflammatory Manifestations of Lymphedema
Authors: Ly Catherine , Kataru Raghu , Mehrara Babak
Published: January 2017

Lymphedema results from lymphatic insufficiency leading to a progressive inflammatory process that ultimately manifests as discomfort, recurrent infections, and, at times, secondary malignancy. Collectively, these morbidities contribute to an overall poor quality of life. Although there have been recent advances in microsurgical interventions, a conservative palliative approach remains the mainstay of treatment for this disabling disease. The absence of a cure is due to an incomplete understanding of the pathophysiological changes that result in lymphedema. A histological hallmark of lymphedema is inflammatory cell infiltration and recent studies with animal models and clinical biopsy specimens have suggested that this response plays a key role in the pathology of the disease. The purpose of this report is to provide an overview of the ongoing research in and the current understanding of the inflammatory manifestations of lymphedema.
Discrepancy between Hepatitis C Virus Genotypes and NS4-Based Serotypes: Association with Their Subgenomic Sequences
Authors: Win Nan , Nakamoto Shingo , Kanda Tatsuo , Takahashi Hiroki , Takahashi-Nakaguchi Azusa , Yasui Shin , Nakamura Masato , Wu Shuang , Imazeki Fumio , Mikami Shigeru , Yokosuka Osamu , Gonoi Tohru , Shirasawa Hiroshi
Published: January 2017

Determination of hepatitis C virus (HCV) genotypes plays an important role in the direct-acting agent era. Discrepancies between HCV genotyping and serotyping assays are occasionally observed. Eighteen samples with discrepant results between genotyping and serotyping methods were analyzed. HCV serotyping and genotyping were based on the HCV nonstructural 4 (NS4) region and 5′-untranslated region (5′-UTR), respectively. HCV core and NS4 regions were chosen to be sequenced and were compared with the genotyping and serotyping results. Deep sequencing was also performed for the corresponding HCV NS4 regions. Seventeen out of 18 discrepant samples could be sequenced by the Sanger method. Both HCV core and NS4 sequences were concordant with that of genotyping in the 5′-UTR in all 17 samples. In cloning analysis of the HCV NS4 region, there were several amino acid variations, but each sequence was much closer to the peptide with the same genotype. Deep sequencing revealed that minor clones with different subgenotypes existed in two of the 17 samples. Genotyping by genome amplification showed high consistency, while several false reactions were detected by serotyping. The deep sequencing method also provides accurate genotyping results and may be useful for analyzing discrepant cases. HCV genotyping should be correctly determined before antiviral treatment.
From Clinical Standards to Translating Next-Generation Sequencing Research into Patient Care Improvement for Hepatobiliary and Pancreatic Cancers
Authors: Kyrochristos Ioannis , Glantzounis Georgios , Ziogas Demosthenes , Gizas Ioannis , Schizas Dimitrios , Lykoudis Efstathios , Felekouras Evangelos , Machairas Anastasios , Katsios Christos , Liakakos Theodoros , Cho William , Roukos Dimitrios
Published: January 2017

Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA. It is a pity that multiple Phase III randomized control trials testing the efficacy of targeted agents have negative results. Failure in the development of effective drugs probably reflects the poor understanding of genome-wide alterations and molecular mechanisms orchestrating therapeutic resistance and recurrence. In the post-ENCODE (Encyclopedia of DNA Elements) era, cancer is referred to as a highly heterogeneous and systemic disease of the genome. The unprecedented potential of next-generation sequencing (NGS) technologies to accurately identify genetic and genomic variations has attracted major research and clinical interest. The applications of NGS include targeted NGS with potential clinical implications, while whole-exome and whole-genome sequencing focus on the discovery of both novel cancer driver genes and therapeutic targets. These advances dictate new designs for clinical trials to validate biomarkers and drugs. This review discusses the findings of available NGS studies on HBP cancers and the limitations of genome sequencing analysis to translate genome-based biomarkers and drugs into patient care in the clinic.
Methylglyoxal-Glyoxalase 1 Balance: The Root of Vascular Damage
Authors: Nigro Cecilia , Leone Alessia , Raciti Gregory , Longo Michele , Mirra Paola , Formisano Pietro , Beguinot Francesco , Miele Claudia
Published: January 2017

The highly reactive dicarbonyl methylglyoxal (MGO) is mainly formed as byproduct of glycolysis. Therefore, high blood glucose levels determine increased MGO accumulation. Nonetheless, MGO levels are also increased as consequence of the ineffective action of its main detoxification pathway, the glyoxalase system, of which glyoxalase 1 (Glo1) is the rate-limiting enzyme. Indeed, a physiological decrease of Glo1 transcription and activity occurs not only in chronic hyperglycaemia but also with ageing, during which MGO accumulation occurs. MGO and its advanced glycated end products (AGEs) are associated with age-related diseases including diabetes, vascular dysfunction and neurodegeneration. Endothelial dysfunction is the first step in the initiation, progression and clinical outcome of vascular complications, such as retinopathy, nephropathy, impaired wound healing and macroangiopathy. Because of these considerations, studies have been centered on understanding the molecular basis of endothelial dysfunction in diabetes, unveiling a central role of MGO-Glo1 imbalance in the onset of vascular complications. This review focuses on the current understanding of MGO accumulation and Glo1 activity in diabetes, and their contribution on the impairment of endothelial function leading to diabetes-associated vascular damage.
Integrins and Cell Metabolism: An Intimate Relationship Impacting Cancer
Authors: Ata Rehman , Antonescu Costin
Published: January 2017

Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions. In this review, we examine the control of integrin function by cell metabolism, and the impact of this regulation in cancer. Within this context, nutrient sufficiency or deprivation is sensed by a number of metabolic signaling pathways such as AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) 1, which collectively control integrin function by a number of mechanisms. Moreover, metabolic flux through specific pathways also controls integrins, such as by control of integrin glycosylation, thus impacting integrin-dependent cell adhesion and migration. Integrins also control various metabolic signals and pathways, establishing the reciprocity of this regulation. As cancer cells exhibit substantial changes in metabolism, such as a shift to aerobic glycolysis, enhanced glucose utilization and a heightened dependence on specific amino acids, the reciprocal regulation of integrins and metabolism may provide important clues for more effective treatment of various cancers.
Using Network Extracted Ontologies to Identify Novel Genes with Roles in Appressorium Development in the Rice Blast Fungus Magnaporthe oryzae
Authors: Ames Ryan
Published: January 2017

Magnaporthe oryzae is the causal agent of rice blast disease, the most important infection of rice worldwide. Half the world’s population depends on rice for its primary caloric intake and, as such, rice blast poses a serious threat to food security. The stages of M. oryzae infection are well defined, with the formation of an appressorium, a cell type that allows penetration of the plant cuticle, particularly well studied. However, many of the key pathways and genes involved in this disease stage are yet to be identified. In this study, I have used network-extracted ontologies (NeXOs), hierarchical structures inferred from RNA-Seq data, to identify pathways involved in appressorium development, which in turn highlights novel genes with potential roles in this process. This study illustrates the use of NeXOs for pathway identification from large-scale genomics data and also identifies novel genes with potential roles in disease. The methods presented here will be useful to study disease processes in other pathogenic species and these data represent predictions of novel targets for intervention in M. oryzae.
Banana Passion Fruit (Passiflora mollissima (Kunth) L.H. Bailey): Microencapsulation, Phytochemical Composition and Antioxidant Capacity
Authors: García-Ruiz Almudena , Girones-Vilaplana Amadeo , León Paola , Moreno Diego , Stinco Carla , Meléndez-Martínez Antonio , Ruales Jenny
Published: January 2017

Passiflora mollissima (Kunth) L.H. Bailey is an exotic fruit native to South America, known as taxo in Ecuador. This paper characterizes its flavonoid and carotenoid composition and antioxidant capacity and evaluates the effect of the spray-drying process on its phytochemical composition and antioxidant capacity. A total of 18 flavonoid compounds, nine proanthocyanidins and nine flavan-3-ol monomers, were identified and quantified. Glycosides of (epi)-afzelechin stood out as the most abundant flavonoid. Three carotenoids were identified, with β-carotene having the highest concentration. The DPPH· and ORAC assay methods indicated a high antioxidant capacity. Furthermore, the bioactive content showed a positive and direct correlation with antioxidant capacity. On the other hand, the spray-drying process produced a stable phytochemical composition and antioxidant activity of taxo. These results demonstrate the potential applicability of microencapsulated taxo as a functional ingredient in the food industry.
Inhibitory Effects of Constituents from the Aerial Parts of Rosmarinus officinalis L. on Triglyceride Accumulation
Authors: Li Jian , Adelakun Tiwalade , Wang Sijian , Ruan Jingya , Yang Shengcai , Li Xiaoxia , Zhang Yi , Wang Tao
Published: January 2017

Sixteen flavonoids (1–16) including two new ones, named officinoflavonosides A (1) and B (2) were obtained from the aerial parts of Rosmarinus officinalis. Among the known ones, 6, 10, and 13 were isolated from the rosmarinus genus for the first time. Their structures were elucidated by chemical and spectroscopic methods. Moreover, the effects on sodium oleate-induced triglyceride accumulation (TG) in HepG2 cells of the above-mentioned compounds and 16 other isolates (17–32) reported previously to have been obtained in the plant were analyzed. Results show that eight kinds of flavonoids (compounds 1, 2, 3, 6–9 and 11) and seven kinds of other known isolates (compounds 17–20, 23, 26 and 31) possessed significant inhibitory effects on intracellular TG content in HepG2 cells. Among them, the activities of compounds 1 and 20 were comparable to that of orlistat, which suggested that these compounds in this plant might be involved in lipid metabolism.
New Phenylpropanoid and Coumarin Glycosides from the Stems of Hydrangea paniculata Sieb
Authors: Ma Jie , Li Chuang-Jun , Yang Jing-Zhi , Sun Hua , Zhang Dong-Ming
Published: January 2017

A new phenylpropanoid glycoside (1), and two new coumarin glycosides (2, 3), together with two known compounds (4, 5), have been isolated from the stems of Hydrangea paniculata Sieb. Their structures have been determined by spectroscopic and chemical methods. Furthermore, compound 1 (50 μM) exhibited significant hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro assays.
Advances in Solid-State Transformations of Coordination Bonds: From the Ball Mill to the Aging Chamber
Authors: Mottillo Cristina , Friščić Tomislav
Published: January 2017

Controlling the formation of coordination bonds is pivotal to the development of a plethora of functional metal-organic materials, ranging from coordination polymers, metal-organic frameworks (MOFs) to metallodrugs. The interest in and commercialization of such materials has created a need for more efficient, environmentally-friendly routes for making coordination bonds. Solid-state coordination chemistry is a versatile greener alternative to conventional synthesis, offering quantitative yields, enhanced stoichiometric and topological selectivity, access to a wider range of precursors, as well as to molecules and materials not readily accessible in solution or solvothermally. With a focus on mechanochemical, thermochemical and “accelerated aging” approaches to coordination polymers, including pharmaceutically-relevant materials and microporous MOFs, this review highlights the recent advances in solid-state coordination chemistry and techniques for understanding the underlying reaction mechanisms.
Mechanochemical Lignin-Mediated Strecker Reaction
Authors: Dabral Saumya , Turberg Mathias , Wanninger Andrea , Bolm Carsten , Hernández José
Published: January 2017

A mechanochemical Strecker reaction involving a wide range of aldehydes (aromatic, heteroaromatic and aliphatic), amines, and KCN afforded a library of α-aminonitriles upon mechanical activation. This multicomponent process was efficiently activated by lignocellulosic biomass as additives. Particularly, commercially available Kraft lignin was found to be the best activator for the addition of cyanide to the in situ formed imines. A comparative study of the 31P-NMR (Nuclear Magnetic Resonance) along with IR (Infrared) data analysis for the Kraft lignin and methylated Kraft lignin samples ascertained the importance of the free hydroxyl groups in the activation of the mechanochemical reaction. The solvent-free mechanochemical Strecker reaction was then coupled with a lactamization process leading to the formation of the N-benzylphthalimide (5a) and the isoindolinone derivative 6a.
O-Carboxymethyl Chitosan Supported Heterogeneous Palladium and Ni Catalysts for Heck Reaction
Authors: Lv Dongjun , Zhang Mingjie
Published: January 2017

Two polymer catalysts (Pd-OCMCS and Ni-OCMCS) with good reusability were synthesized by coordinating Pd and Ni onto O-carboxymethyl chitosan (OCMCS). The chemical structure and thermal stability of prepared catalysts were determined by Fourier transform infrared (FT-IR) spectra, Energy Dispersive Spectrometer (EDS)analysis, X-ray diffraction (XRD), and thermogravimetric analyzer (TG-DTG), and the analysis results showed that the Pd and Ni ions coordinated onto the OCMCS and formed a ligand with the –COOH group, amino groups, and –OH group on the OCMCS, and the EDS and Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) analysis results showed that the loading amounts of Pd and Ni were approximately 8.3% and 8.9%, respectively. In the Heck reaction between aryl halides and n-butyl acrylate catalyzed by the prepared catalyst, the test results showed that the product yield followed the order of aryl iodide > aryl bromide > aryl chloride. Additionally, the product yield for the aryl iodide and aryl bromide could reach up to 99% and 96%, respectively. Moreover, the electron-withdrawing and electron-donating property of the group on the aryl also affected the product yield, and the product yield for aryl halides with electron-withdrawing group p-NO2, p-CH3CO, and p-CHO was higher than that with electron-donating group p-CH3.
Novel Amino-Pyridine Functionalized Chitosan Quaternary Ammonium Derivatives: Design, Synthesis, and Antioxidant Activity
Authors: Li Qing , Zhang Caili , Tan Wenqiang , Gu Guodong , Guo Zhanyong
Published: January 2017

Chemical modification of chitosan is increasingly studied for its potential of providing new applications of chitosan. Here, a group of novel chitosan quaternary ammonium derivatives containing pyridine or amino-pyridine were designed and successfully synthesized through chemical modification of chitosan. Pyridine and amino-pyridine were used as functional groups to improve the antifungal activity of chitosan derivatives. The chitosan derivatives’ antioxidant activity against hydroxyl-radical and 1,1-Diphenyl-2-picrylhydrazyl (DPPH)-radical was tested in vitro. The results showed that chitosan derivatives had better water solubility and stronger antioxidant activity compared with chitosan in all assays. Especially, compounds 3C and 3E (with 3-amino pyridine and 2,3-diamino pyridine as substitute respectively) exhibited stronger hydroxyl-radical and DPPH-radical scavenging ability than other synthesized compounds. These data demonstrated that the synergistic effect of the amino group and pyridine would improve the antioxidant activity of chitosan derivatives, and the position of the amino group on pyridine could influence the antioxidant property of chitosan derivatives.
Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development
Authors: Leek Hanna , Andersson Shalini
Published: January 2017

The provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agro-chemistry and biotechnology. In drug discovery and development, the enantiomers of a chiral drug depict unique chemical and pharmacological behaviors in a chiral environment, such as the human body, in which the stereochemistry of the chiral drugs determines their pharmacokinetic, pharmacodynamic and toxicological properties. We present a number of challenging case studies of up-to-kilogram separations of racemic or enriched isomer mixtures using preparative liquid chromatography and super critical fluid chromatography to generate individual enantiomers that have enabled the development of new candidate drugs within AstraZeneca. The combination of chromatography and racemization as well as strategies on when to apply preparative chiral chromatography of enantiomers in a multi-step synthesis of a drug compound can further facilitate accelerated drug discovery and the early clinical evaluation of the drug candidates.
Design of Wearable Breathing Sound Monitoring System for Real-Time Wheeze Detection
Authors: Li Shih-Hong , Lin Bor-Shing , Tsai Chen-Han , Yang Cheng-Ta , Lin Bor-Shyh
Published: January 2017

In the clinic, the wheezing sound is usually considered as an indicator symptom to reflect the degree of airway obstruction. The auscultation approach is the most common way to diagnose wheezing sounds, but it subjectively depends on the experience of the physician. Several previous studies attempted to extract the features of breathing sounds to detect wheezing sounds automatically. However, there is still a lack of suitable monitoring systems for real-time wheeze detection in daily life. In this study, a wearable and wireless breathing sound monitoring system for real-time wheeze detection was proposed. Moreover, a breathing sounds analysis algorithm was designed to continuously extract and analyze the features of breathing sounds to provide the objectively quantitative information of breathing sounds to professional physicians. Here, normalized spectral integration (NSI) was also designed and applied in wheeze detection. The proposed algorithm required only short-term data of breathing sounds and lower computational complexity to perform real-time wheeze detection, and is suitable to be implemented in a commercial portable device, which contains relatively low computing power and memory. From the experimental results, the proposed system could provide good performance on wheeze detection exactly and might be a useful assisting tool for analysis of breathing sounds in clinical diagnosis.
Two-Dimensional Numerical Simulations of Ultrasound in Liquids with Gas Bubble Agglomerates: Examples of Bubbly-Liquid-Type Acoustic Metamaterials (BLAMMs)
Authors: Vanhille Christian
Published: January 2017

This work deals with a theoretical analysis about the possibility of using linear and nonlinear acoustic properties to modify ultrasound by adding gas bubbles of determined sizes in a liquid. We use a two-dimensional numerical model to evaluate the effect that one and several monodisperse bubble populations confined in restricted areas of a liquid have on ultrasound by calculating their nonlinear interaction. The filtering of an input ultrasonic pulse performed by a net of bubbly-liquid cells is analyzed. The generation of a low-frequency component from a single cell impinged by a two-frequency harmonic wave is also studied. These effects rely on the particular dispersive character of attenuation and nonlinearity of such bubbly fluids, which can be extremely high near bubble resonance. They allow us to observe how gas bubbles can change acoustic signals. Variations of the bubbly medium parameters induce alterations of the effects undergone by ultrasound. Results suggest that acoustic signals can be manipulated by bubbles. This capacity to achieve the modification and control of sound with oscillating gas bubbles introduces the concept of bubbly-liquid-based acoustic metamaterials (BLAMMs).
Delivering integrated child development care in Pakistan: protocol for a clustered randomised trial
Authors: Khan Muhammad Amir , Owais Syeda Somyyah , Blacklock Claire , Anil Shirin , Ishaq Sehrish , Maqbool Shazia , Khan Haroon Jehangir , Minhas Fareed A , Walley John
Published: January 2017

Background

Early childhood developmental delay is associated with significant disadvantage in adult life. In Pakistan, high prevalence of developmental delay is associated with poverty, under-nutrition, and maternal depression.

Aim

To assess the effectiveness of an early child development counselling intervention delivered at private GP clinics, in poor urban communities.

Design & setting

A clustered randomised trial in Pakistan.

Method

The intervention was developed following a period of formative research, and in consultation with local experts. A total of 2112 mother–child pairs will be recruited at 32 clinics, from within the locality (cluster); 16 clinics per arm. A primary care counselling intervention (promoting child development, nutrition, and maternal mental health) will be delivered at 6 weeks, 3, 6, and 9 months of the child’s age. Monitoring, assessment, and treatment will also be performed at quarterly visits in intervention clinics. Primary outcome is the developmental delay at 12 months (ASQ-3 scores). Secondary outcomes are stunting rate, and maternal depression (PHQ-9 score). In addition, a process evaluation and costing study will be conducted.

Discussion

This trial will be the first to assess an early child development intervention, delivered in private GP clinics for poor urban communities in Pakistan. If found to be effective, this public–private model may offer a more sustainable, and feasible option for populations in poor urban settings, where private GP clinics are the most accessible provider of primary health care. There is scope for scale-up at provincial level, should the intervention be effective.

Trial registration

The trial has been registered with the Current Controlled Trials ISRCTN48032200.