bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel circulating microRNA signature as a potential non‐invasive multi‐marker test in ER‐positive early‐stage breast cancer: A case control study
Authors: Kodahl Annette R. , Lyng Maria B. , Binder Harald , Cold Søren , Gravgaard Karina , Knoop Ann S. , Ditzel Henrik J.
Published: March 2014

Introduction

There are currently no highly sensitive and specific minimally invasive biomarkers for detection of early‐stage breast cancer. MicroRNAs (miRNAs) are present in the circulation and may be unique biomarkers for early diagnosis of human cancers. The aim of this study was to investigate the differential expression of miRNAs in the serum of breast cancer patients and healthy controls.

Methods

Global miRNA analysis was performed on serum from 48 patients with ER‐positive early‐stage breast cancer obtained at diagnosis (24 lymph node‐positive and 24 lymph node‐negative) and 24 age‐matched healthy controls using LNA‐based quantitative real‐time PCR (qRT‐PCR). A signature of miRNAs was subsequently validated in an independent set of 111 serum samples from 60 patients with early‐stage breast cancer and 51 healthy controls and further tested for reproducibility in 3 independent data sets from the GEO Database.

Results

A multivariable signature consisting of 9 miRNAs (miR‐15a, miR‐18a, miR‐107, miR‐133a, miR‐139‐5p, miR‐143, miR‐145, miR‐365, miR‐425) was identified that provided considerable discrimination between breast cancer patients and healthy controls. Further, the ability of the 9 miRNA signature to stratify samples from breast cancer patients and healthy controls was confirmed in the validation set (p = 0.012) with a corresponding AUC = 0.665 in the ROC‐curve analysis. No association between miRNA expression and tumor grade, tumor size, menopausal‐ or lymph node status was observed. The signature was also successfully validated in a previously published independent data set of circulating miRNAs in early‐stage breast cancer (p = 0.024).

Conclusions

We present herein a 9 miRNA signature capable of discriminating between ER‐positive breast cancer and healthy controls. Using a specific algorithm based on the 9 miRNA signature, the risk for future individuals can be predicted. Since microRNAs are highly stable in blood components, this signature might be useful in the development of a blood‐based multi‐marker test to improve early detection of breast cancer. Such a test could potentially be used as a screening tool to identify individuals who would benefit from further diagnostic assessment.
SOUND, MEANING AND MUSIC-DRAMA IN LACHENMANN'S DAS MÄDCHEN MIT DEN SCHWEFELHÖLZERN
Authors: Osborn Laurence
Published: March 2014

This article argues that Das Mädchen mit den Schwefelhölzern demonstrates a unique approach to music-drama that stems from the perceptual capacities of listeners, and their desire to search for meaning in what they hear. Beginning with the claim that Das Mädchen mit den Schwefelhölzern can be viewed as the culmination of an aesthetic project begun at the point of Lachenmann's emergence as a distinctive voice of the European avant-garde during the 1960s, the article first examines two major aspects of Lachenmann's aesthetics – musique concrète instrumentale and aura – outlining a composing philosophy that has been at the heart of Lachenmann's practice throughout his career. The article claims that Lachenmann sought to establish a rejuvenated semiotics, freed from cultural baggage and tied to the perceptual and cognitive capacities of listeners. Drawing upon the studies of Naomi Cumming and Luke Windsor, it outlines a theoretical framework that takes into account this composing philosophy and its implications, applying it in analyses of various excerpts from Das Mädchen mit den Schwefelhölzern. My analysis illuminates a music-drama that forms around the interplay of internally represented images and sensations, the emergence of which is facilitated by a musical language that prepares sounds to take on certain types of meaning. The article concludes with a brief discussion of the possible implications this has for audience members.
SYMMETRY IN THE MUSIC OF JOHN ADAMS
Authors: Sanchez-Behar Alexander
Published: March 2014

Close examination of John Adams's oeuvre reveals that symmetry is one of the predominant features of his music. Three common types of symmetry are encountered in Adams's works: reflection, translation and rotation. This article investigates these symmetries and tracks their development throughout Adams's compositional career. An analysis of selected works from the 1970s (China Gates and Phrygian Gates), 1980s (Grand Pianola Music and Fearful Symmetries) and 1990s (the Violin Concerto and Century Rolls) highlights the most pervasive symmetry in each decade and shows a shift from preconceived overarching symmetries that frame entire musical structures to smaller-level symmetries that affect the music at a level of phrase and motivic structure.
Secession and the invisible hand of the international system
Authors: GRIFFITHS RYAN
Published: March 2014

This article argues that 1945 constitutes an historical inflection point from a period of state expansion to state contraction and that this transformation is primarily the result of changes at the international level. Just as security and economic pressures drove lead states to expand in earlier times, changing conditions in the post-1945 period led to a contraction in state size. The change from multipolarity, the development of the territorial integrity norm, the shift to nuclear deterrence, and the burgeoning global economy contributed to the milieu in which states evaluate the costs and benefits of holding territory, and this has enabled states to permit secession more frequently. The result has been an increase in the rate of peaceful secession and a corresponding proliferation in the number of sovereign states. I test this argument both qualitatively and quantitatively using original data on secessionist movements and internal administrative regions between 1816 and 2005.
Network information analysis reveals risk perception transmission in a behaviour-influenza dynamics system
Authors: LIAO C.-M. , YOU S.-H. , CHENG Y.-H.
Published: March 2014

Influenza poses a significant public health burden worldwide. Understanding how and to what extent people would change their behaviour in response to influenza outbreaks is critical for formulating public health policies. We incorporated the information-theoretic framework into a behaviour-influenza (BI) transmission dynamics system in order to understand the effects of individual behavioural change on influenza epidemics. We showed that information transmission of risk perception played a crucial role in the spread of health-seeking behaviour throughout influenza epidemics. Here a network BI model provides a new approach for understanding the risk perception spread and human behavioural change during disease outbreaks. Our study allows simultaneous consideration of epidemiological, psychological, and social factors as predictors of individual perception rates in behaviour-disease transmission systems. We suggest that a monitoring system with precise information on risk perception should be constructed to effectively promote health behaviours in preparation for emerging disease outbreaks.
Survivability and molecular variation inVibrio choleraefrom epidemic sites in China
Authors: LI X. Q. , WANG M. , DENG Z. A. , SHEN J. C. , ZHANG X. Q. , LIU Y. F. , CAI Y. S. , WU X. W. , DI B.
Published: March 2014

The survival behaviour ofVibrio choleraein cholera epidemics, together with its attributes of virulence-associated genes and molecular fingerprints, are significant for managing cholera epidemics. Here, we selected five strains representative ofV. choleraeO1 and O139 involved in cholera events, examined their survival capacity in large volumes of water sampled from epidemic sites of a 2005 cholera outbreak, and determined virulence-associated genes and molecular subtype changes of the surviving isolates recovered. The five strains exhibited different survival capacities varying from 17 to 38 days. The virulence-associated genes of the surviving isolates remained unchanged, while their pulsotypes underwent slight variation. In particular, one waterway-isolated strain maintained virulence-associated genes and evolved to share the same pulsotype as patient strains, highlighting its role in the cholera outbreak. The strong survival capacity and molecular attributes ofV. choleraemight account for its persistence in environmental waters and the long duration of the cholera outbreak, allowing effective control measures.
Superconducting graphene sheets in CaC6 enabled by phonon-mediated interband interactions
Authors: Yang S.-L. , Sobota J. A. , Howard C. A. , Pickard C. J. , Hashimoto M. , Lu D. H. , Mo S.-K. , Kirchmann P. S. , Shen Z.-X.
Published: March 2014

There is a great deal of fundamental and practical interest in the possibility of inducing superconductivity in a monolayer of graphene. But while bulk graphite can be made to superconduct when certain metal atoms are intercalated between its graphene sheets, the same has not been achieved in a single layer. Moreover, there is a considerable debate about the precise mechanism of superconductivity in intercalated graphite. Here we report angle-resolved photoelectron spectroscopy measurements of the superconducting graphite intercalation compound CaC6 that distinctly resolve both its intercalant-derived interlayer band and its graphene-derived π* band. Our results indicate the opening of a superconducting gap in the π* band and reveal a substantial contribution to the total electron–phonon-coupling strength from the π*-interlayer interband interaction. Combined with theoretical predictions, these results provide a complete account for the superconducting mechanism in graphite intercalation compounds and lend support to the idea of realizing superconducting graphene by creating an adatom superlattice.
Nanofabrication and its Application in Renewable Energy
Authors:   Royal Society of Chemistry
Published: March 2014

Nanoscale materials and structures have attracted great attention in recent years because of their unique physical and chemical properties and potential use in energy transport and conversion. This book puts the subject into context by first looking at current synthesis methods for nanomaterials, from the bottom-up and top-down methods, followed by enhanced energy conversion efficiency at the nanoscale and then specific applications e.g. photovoltaic cells and nanogenerators. This authoritative and comprehensive book will be of interest to both the existing scientific community in this field, as well as for new people who wish to enter it.
Nanophotonic Light Trapping Theory for Photovoltaics
Authors: Yu Zongfu , Raman Aaswath , Fan Shanhui
Published: March 2014

Photonics plays an increasingly important role in the design of solar cells. Advanced optical designs at the nanoscale can enhance light-matter interaction and increase sunlight absorption. This technique is generally referred to as light trapping. Light trapping helps to reduce the material cost of solar cells. More importantly, it improves the collection efficiency of photo-generated carriers. This chapter will review the general nanophotonic light trapping theory developed by the authors.
Measurements of Photovoltaic Cells
Authors: Xuebo Huang , Jing Zhang
Published: March 2014

This chapter describes the methods of evaluating the performance of photovoltaic cells and modules. The key evaluating factor of photovoltaic cells is the energy converting efficiency under standard testing conditions. The efficiency is the ratio of the maximum electrical output power of a solar cell to the incident optical power in the form of sunlight. The properties of sunlight and solar simulators, and characteristics of photovoltaic solar cells are described. The calibration method, setup and traceability are also discussed.
MeOx-TMS derivatization for GC-MS metabolic profiling of urine and application in the discrimination between normal C57BL/6J and type 2 diabetic KK-Ay mice
Authors: Yi Lunzhao , Shi Shuting , Yi Zhibiao , He Ruihua , Lu Hongmei , Liang Yizeng
Published: March 2014

GC-MS-based protocol using methoximation followed by silylation with BSTFA + 1%TMCS for the analysis of urine metabolites.
Kinetics study of solid ammonia borane hydrogen release – modeling and experimental validation for chemical hydrogen storage
Authors: Choi Young Joon , Rönnebro Ewa C. E. , Rassat Scot , Karkamkar Abhi , Maupin Gary , Holladay Jamie , Simmons Kevin , Brooks Kriston
Published: March 2014

Hydrogen capacity and bulk kinetics comparisons of ammonia borane at 160 °C, 200 °C, 250 °C and 300 °C.
Variations in topology and magnetic properties of hepta- and octacyanometallates of molybdenum with manganese(ii)
Authors: Wang Qing-Lun , Zhang Yuan-Zhu , Southerland Heather , Prosvirin Andrey V. , Zhao Hanhua , Dunbar Kim R.
Published: March 2014

Treatment of [Mn(dpop)(H2O)2]Cl2with K4[Mo(CN)7]·2H2O under varied synthetic conditions afforded four different compounds that exhibit a diversity of structures and magnetic properties.
High frequency variability of environmental drivers determining benthic community dynamics in headwater streams
Authors: Snell M. A. , Barker P. A. , Surridge B. W. J. , Large A. R. G. , Jonczyk J. , Benskin C. McW. H. , Reaney S. , Perks M. T. , Owen G. J. , Cleasby W. , Deasy C. , Burke S. , Haygarth P. M.
Published: March 2014

Headwater streams are an important feature of the landscape, with their diversity in chlorophyll-a and community structure a function of mean antecedent conditions.
Effect of taurine in chronic alcoholic patients
Authors: Hsieh You-Liang , Yeh Yen-Hung , Lee Ya-Ting , Huang Chih-Yang
Published: March 2014

A study was undertaken to investigate the dietary effect of taurine in chronic alcoholic patients.
The battle for the “green” polymer. Different approaches for biopolymer synthesis: bioadvantaged vs. bioreplacement
Authors: Hernández Nacú , Williams R. Christopher , Cochran Eric W.
Published: March 2014

In this perspective we compare and contrast two distinct approaches to the economical realization of biomaterials.
Recent developments in solid-state NMR spectroscopy of crystalline microporous materials
Authors: Ashbrook Sharon E. , Dawson Daniel M. , Seymour Valerie R.
Published: March 2014

This Perspective describes how solid-state NMR spectroscopy can be used to investigate the structure, disorder, dynamics and reactivity of crystalline microporous framework materials.
Effect of stepped substrates on the interfacial adhesion properties of graphene membranes
Authors: He Yan , Yu Wangbing , Ouyang Gang
Published: March 2014

The dependence of the interfacial adhesion properties of graphene membranes on thickness and substrate surface parameters are investigated.
Photocatalytic degradation of organic dyes by La3+/Ce3+-H3PW12O40under different light irradiation
Authors: Li Taohai , Li Quanguo , Yan Jing , Li Feng
Published: March 2014

La3+-H3PW12O40and Ce3+-H3PW12O40photocatalysts were synthesized by the PEG-1000 assisted hydrothermal method. These prepared photocatalysts exhibited highly efficient light-driven photocatalytic activity for the degradation of dyes (MO and RhB) under UV- and visible light irradiation.
The interactome of the atypical phosphatase Rtr1 in Saccharomyces cerevisiae
Authors: Smith-Kinnaman Whitney R. , Berna Michael J. , Hunter Gerald O. , True Jason D. , Hsu Peter , Cabello Gabriela I. , Fox Melanie J. , Varani Gabriele , Mosley Amber L.
Published: March 2014

The interactome of the CTD phosphatase Rtr1 is regulated by the CTDK-I subunit Ctk1.
Popcorn-like PtAu nanoparticles supported on reduced graphene oxide: Facile synthesis and catalytic applications
Authors: Zheng Jie-Ning , Li Shan-Shan , Ma Xiaohong , Chen Fang-Yi , Wang Ai-Jun , Chen Jian-Rong , Feng Jiu-Ju
Published: March 2014

Popcorn-like PtAu nanoparticles were fabricated and further supported on rGO by ultrasonication. The as-prepared nanocomposites showed an enhanced electrocatalytic performance for ORR and methanol oxidation.
Structural and mechanistic insight into alkane hydroxylation by Pseudomonas putida AlkB
Authors: Alonso Hernan , Kleifeld Oded , Yeheskel Adva , Ong Poh C. , Liu Yu C. , Stok Jeanette E. , De Voss James J. , Roujeinikova Anna
Published: March 2014

Pseudomonas putida GPo1 alkane hydroxylase (AlkB) is an integral membrane protein that catalyses the hydroxylation of medium-chain alkanes (C3–C12). 1-Octyne irreversibly inhibits this non-haem di-iron mono-oxygenase under turnover conditions, suggesting that it acts as a mechanism-based inactivator. Upon binding to the active site, 1-octyne is postulated to be oxidized to an oxirene that rapidly rearranges to a reactive ketene which covalently acylates nearby residues, resulting in enzyme inactivation. In analysis of inactivated AlkB by LC–MS/MS, several residues exhibited a mass increase of 126.1 Da, corresponding to the octanoyl moiety derived from oxidative activation of 1-octyne. Mutagenesis studies of conserved acylated residues showed that Lys18 plays a critical role in enzyme function, as a single-point mutation of Lys18 to alanine (K18A) completely abolished enzymatic activity. Finally, we present a computational 3D model structure of the transmembrane domain of AlkB, which revealed the overall packing arrangement of the transmembrane helices within the lipid bilayer and the location of the active site mapped by the 1-octyne modifications.
S-locus receptor kinase signalling
Authors: Nasrallah June B. , Nasrallah Mikhail E.
Published: March 2014

SRK (S-locus receptor kinase) is the receptor that allows stigma epidermal cells to discriminate between genetically related (‘self’) and genetically unrelated (‘non-self’) pollen in the self-incompatibility response of the Brassicaceae. SRK and its ligand, the pollen coat-localized SCR (S-locus cysteine-rich protein), are highly polymorphic, and their allele-specific interaction explains specificity in the self-incompatibility response. The present article reviews current knowledge of the role of SRK in the recognition and response phases of self-incompatibility, and highlights the new insights provided by analysis of a transgenic self-incompatible Arabidopsis thaliana model.
Interactions between pollen tube and pistil control pollen tube identity and sperm release in the Arabidopsis female gametophyte
Authors: Leydon Alexander R. , Chaibang Adisorn , Johnson Mark A.
Published: March 2014

Flowering plants have immotile sperm that develop within the pollen cytoplasm and are delivered to female gametes by a pollen tube, a highly polarized extension of the pollen cell. In many flowering plant species, including seed crop plants, hundreds of pollen tubes grow towards a limited number of ovules. This system should ensure maximal fertilization of ovules and seed production; however, we know very little about how signalling between the critical cells is integrated to orchestrate delivery of two functional sperm to each ovule. Recent studies suggest that the pollen tube changes its gene-expression programme in response to growth through pistil tissue and that this differentiation process is critical for pollen tube attraction by the female gametophyte and for release of sperm. Interestingly, these two signalling systems, called pollen tube guidance and pollen tube reception, are also species-preferential. The present review focuses on Arabidopsis pollen tube differentiation within the pistil and addresses the idea that pollen tube differentiation defines pollen tube identity and recognition by female cells. We review recent identification of genes that may control pollen tube–female gametophyte recognition and discuss how these may be involved in blocking interspecific hybridization.
Neonatal encephalopathy: pre-clinical studies in neuroprotection
Authors: Patel Shyama D. , Pierce Leslie , Ciardiello Amber J. , Vannucci Susan J.
Published: March 2014

Neonatal encephalopathy resulting from HI (hypoxia–ischaemia) continues to be a significant cause of mortality and morbidity in infants and children, affecting 1–2/1000 live term births and up to 60% of pre-term births. In order to understand the pathophysiology of this insult, as well as design therapeutic interventions, it is important to establish a relevant animal model for pre-clinical studies. One of the most frequently used models of HI-induced brain damage in immature animals is the unilateral carotid ligation/hypoxia model, initially developed in our laboratory more than 30 years ago. The original model employed the postnatal day 7 rat, whose brain is representative of that of a late gestation, pre-term [32–36 weeks GA (gestational age)] human infant. We, and others, have employed this model to characterize the pathophysiological, biochemical/energetic and neuropathological events following HI, as well as the determination of the unique characteristics of the immature brain that define its vulnerability to, and outcome from, HI. In defining the cascade of events following HI, it has become possible to identify potential targets for intervention and neuroprotection. Currently, the only available therapeutic intervention for neonatal encephalopathy in the term asphyxiated infant is therapeutic hypothermia, although this must be initiated within 6 h of birth and is at best partially effective in moderately injured infants. Ongoing pre-clinical studies are necessary to determine the basis for the partial protection afforded by hypothermia as well as the design of adjunct therapies to improve the outcome. The present review highlights the importance of using a well-characterized and relevant animal model to continue to pursue translational research in neuroprotection for the infant brain.
MicroRNA functions in plant embryos
Authors: Vashisht Divya , Nodine Michael D.
Published: March 2014

Plant miRNAs are short non-coding RNAs that mediate the repression of hundreds of genes. The basic plant body plan is established during early embryogenesis, and recent results have demonstrated that miRNAs play pivotal roles during both embryonic pattern formation and developmental timing. Multiple miRNAs appear to specifically repress transcription factor families during early embryogenesis. Therefore miRNAs probably have a large influence on the gene regulatory networks that contribute to the earliest cellular differentiation events in plants.
Cyclic nucleotide phosphodiesterases (PDEs): coincidence detectors acting to spatially and temporally integrate cyclic nucleotide and non-cyclic nucleotide signals
Authors: Maurice Donald H. , Wilson Lindsay S. , Rampersad Sarah N. , Hubert Fabien , Truong Tammy , Kaczmarek Milosz , Brzezinska Paulina , Freitag Silja I. , Umana M. Bibiana , Wudwud Alie
Published: March 2014

The cyclic nucleotide second messengers cAMP and cGMP each affect virtually all cellular processes. Although these hydrophilic small molecules readily diffuse throughout cells, it is remarkable that their ability to activate their multiple intracellular effectors is spatially and temporally selective. Studies have identified a critical role for compartmentation of the enzymes which hydrolyse and metabolically inactivate these second messengers, the PDEs (cyclic nucleotide phosphodiesterases), in this specificity. In the present article, we describe several examples from our work in which compartmentation of selected cAMP- or cGMP-hydrolysing PDEs co-ordinate selective activation of cyclic nucleotide effectors, and, as a result, selectively affect cellular functions. It is our belief that therapeutic strategies aimed at targeting PDEs within these compartments will allow greater selectivity than those directed at inhibiting these enzymes throughout the cells.
Platelet myosin light chain phosphatase: keeping it together
Authors: Aburima Ahmed , Naseem Khalid M.
Published: March 2014

MLCP (myosin light chain phosphatase) regulates platelet function through its ability to control myosin IIa phosphorylation. Recent evidence suggests that MLCP is a de facto target for signalling events stimulated by cAMP. In the present mini-review, we discuss the mechanisms by which cAMP signalling maintains MLCP in an active state to control platelet contractile machinery.
cAMP signalling meets mitochondrial compartments
Authors: Lefkimmiatis Konstantinos
Published: March 2014

Mitochondria are highly dynamic organelles comprising at least three distinct areas, the OMM (outer mitochondrial membrane), the IMS (intermembrane space) and the mitochondrial matrix. Physical compartmentalization allows these organelles to host different functional domains and therefore participate in a variety of important cellular actions such as ATP synthesis and programmed cell death. In a surprising homology, it is now widely accepted that the ubiquitous second messenger cAMP uses the same stratagem, compartmentalization, in order to achieve the characteristic functional pleiotropy of its pathway. Accumulating evidence suggests that all the main mitochondrial compartments contain segregated cAMP cascades; however, the regulatory properties and functional significance of such domains are not fully understood and often remain controversial issues. The present mini-review discusses our current knowledge of how the marriage between mitochondrial and cAMP compartmentalization is achieved and its effects on the biology of the cell.
Bacterial glyoxalase I enzymes: structural and biochemical investigations
Authors: Honek John F.
Published: March 2014

A number of bacterial glyoxalase I enzymes are maximally activated by Ni2+ and Co2+ ions, but are inactive in the presence of Zn2+, yet these enzymes will also bind this metal ion. The structure–activity relationships between these two classes of glyoxalase I serve as important clues as to how the molecular structures of these proteins control metal-activation profiles.
Glyoxalase diversity in parasitic protists
Authors: Deponte Marcel
Published: March 2014

Our current knowledge of the isomerase glyoxalase I and the thioesterase glyoxalase II is based on a variety of prokaryotic and eukaryotic (model) systems with an emphasis on human glyoxalases. During the last decade, important insights on glyoxalase catalysis and structure–function relationships have also been obtained from parasitic protists. These organisms, including kinetoplastid and apicomplexan parasites, are particularly interesting, both because of their relevance as pathogens and because of their phylogenetic diversity and host–parasite co-evolution which has led to specialized organellar and metabolic adaptations. Accordingly, the glyoxalase repertoire and properties vary significantly among parasitic protists of different major eukaryotic lineages (and even between closely related organisms). For example, several protists have an insular or non-canonical glyoxalase. Furthermore, the structures and the substrate specificities of glyoxalases display drastic variations. The aim of the present review is to highlight such differences as well as similarities between the glyoxalases of parasitic protists and to emphasize the power of comparative studies for gaining insights into fundamental principles and alternative glyoxalase functions.
Assay of methylglyoxal and glyoxal and control of peroxidase interference
Authors: Thornalley Paul J. , Rabbani Naila
Published: March 2014

Methylglyoxal and glyoxal are endogenous α-oxoaldehyde metabolites and substrates of the glyoxalase system. These and related α-oxoaldehydes are often determined in cell, tissue and body fluid samples by derivatization with 1,2-diaminobenzene and similar compounds. Peroxidase activity in physiological tissues is a potential interference in estimation of methylglyoxal and glyoxal as it catalyses the conversion of 1,2-diaminobenzene into trace amounts of these dicarbonyl metabolites. Residual peroxidase activity in deproteinized extracts is found to cause significant interference in methylglyoxal and glyoxal estimations. This interference is blocked by the addition of sodium azide in the derivatizing buffer. Estimates of methylglyoxal concentration thereby obtained are in keeping with those predicted by systems modelling of methylglyoxal glycation kinetics in situ. Blocking sample peroxidase activity is important to avoid overestimation in the measurement of glyoxal and methylglyoxal. A dicarbonyl assay protocol resistant to interferences is described in the present article.
Copy number variation of glyoxalase I
Authors: Shafie Alaa , Xue Mingzhan , Thornalley Paul J. , Rabbani Naila
Published: March 2014

The glyoxalase I gene GLO1 is a hotspot for copy number variation in the human and mouse genomes. The additional copies are often functional, giving rise to 2–4-fold increased glyoxalase I expression and activity. The prevalence of GLO1 copy number increase in the human population appears to be approximately 2% and may be linked to a risk of obesity, diabetes and aging. Increased GLO1 copy number has been found in human tumour cell lines and primary human tumours. The minimum common copy number increase region was approximately 1 Mb and it contained GLO1 and seven other genes. The increased copy number was generally functional, being associated with increased glyoxalase I protein and multidrug resistance in cancer chemotherapy. Glo1 duplication in the mouse genome is found within approximately 0.5 Mb of duplicated DNA. It was claimed to be linked to anxiety phenotypes, but other related discordant findings have doubted the association with glyoxalase I and further investigation is required.
Glyoxalase Centennial conference: introduction, history of research on the glyoxalase system and future prospects
Authors: Rabbani Naila , Thornalley Paul J.
Published: March 2014

On 27–29 November 2013, researchers gathered at the University of Warwick, Coventry, U.K., to celebrate the centennial of the discovery of the glyoxalase pathway. The glyoxalase system was discovered and reported in papers by Carl Neuberg and by Henry Drysdale Dakin and Harold Ward Dudley in 1913. All three were leading extraordinary investigators in the pioneering years of biochemistry. Neuberg proposed glyoxalase as the pathway of mainstream glycolysis and Gustav Embden correctly discounted this, later confirmed by Otto Meyerhof. Albert Szent-Györgyi proposed glyoxalase I as the regulator of cell growth and others discounted this. In the meantime, molecular, structural and mechanistic properties of the enzymatic components of the system, glyoxalase I and glyoxalase II, have been characterized. The physiological function of the glyoxalase pathway of enzymatic defence against dicarbonyl glycation, particularly by endogenous methylglyoxal, now seems secure. We are now in an era of investigation of the regulation of the glyoxalase system where a role in aging and disease, physiological stress and drug resistance and development of healthier foods and new pharmaceuticals is emerging. The history of glyoxalase research illustrates the scientific process of hypothesis proposal, testing and rejection or acceptance with further investigation, standing testament to the need for intuition guided by experience and expertise, as well as indefatigable experimentation.
Dicarbonyl proteome and genome damage in metabolic and vascular disease
Authors: Rabbani Naila , Thornalley Paul J.
Published: March 2014

Methylglyoxal is a potent protein-glycating agent. It is an arginine-directed glycating agent and often modifies functionally important sites in proteins. Glycation forms mainly MG-H1 [Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine] residues. MG-H1 content of proteins is quantified by stable isotopic dilution analysis–MS/MS and also by immunoblotting with specific monoclonal antibodies. Methylglyoxal-modified proteins undergo cellular proteolysis and release MG-H1 free adduct for excretion. MG-H1 residues have been found in proteins of animals, plants, bacteria, fungi and protoctista. MG-H1 is often the major advanced glycation end-product in proteins of tissues and body fluids, increasing in diabetes and associated vascular complications, renal failure, cirrhosis, Alzheimer's disease, arthritis, Parkinson's disease and aging. Proteins susceptible to methylglyoxal modification with related functional impairment are called the DCP (dicarbonyl proteome). The DCP includes albumin, haemoglobin, transcription factors, mitochondrial proteins, extracellular matrix proteins, lens crystallins and others. DCP component proteins are linked to mitochondrial dysfunction in diabetes and aging, oxidative stress, dyslipidaemia, cell detachment and anoikis and apoptosis. Methylglyoxal also modifies DNA where deoxyguanosine residues are modified to imidazopurinone MGdG {3-(2′-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6/7-methylimidazo-[2,3-b]purine-9(8)one} isomers. MGdG was the major quantitative adduct detected in vivo. It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell-permeant glyoxalase I inhibitor. Glyoxalase I metabolizes >99% methylglyoxal and thereby protects the proteome and genome. Gene deletion of GLO1 is embryonically lethal and GLO1 silencing increases methylglyoxal concentration, MG-H1 and MGdG, premature aging and disease. Studies of methylglyoxal glycation have importance for human health, longevity and treatment of disease.
Glo1 inhibitors for neuropsychiatric and anti-epileptic drug development
Authors: McMurray Katherine M.J. , Distler Margaret G. , Sidhu Preetpal S. , Cook James M. , Arnold Leggy A. , Palmer Abraham A. , Plant Leigh D.
Published: March 2014

Many current pharmacological treatments for neuropsychiatric disorders, such as anxiety and depression, are limited by a delayed onset of therapeutic effect, adverse side effects, abuse potential or lack of efficacy in many patients. These off-target effects highlight the need to identify novel mechanisms and targets for treatment. Recently, modulation of Glo1 (glyoxalase I) activity was shown to regulate anxiety-like behaviour and seizure-susceptibility in mice. These effects are likely to be mediated through the regulation of MG (methylglyoxal) by Glo1, as MG acts as a competitive partial agonist at GABAA (γ-aminobutyric acid A) receptors. Thus modulation of MG by Glo1 represents a novel target for treatment. In the present article, we evaluate the therapeutic potential of indirectly modulating MG concentrations through Glo1 inhibitors for the treatment of neuropsychiatric disorders.
A fluorogenic assay for methylglyoxal
Authors: Shaheen Fozia , Shmygol Anatoly , Rabbani Naila , Thornalley Paul J.
Published: March 2014

MG (methylglyoxal) is a potent glycating agent and an endogenous reactive dicarbonyl metabolite formed in all live cells and organisms. It is an important precursor of AGEs (advanced glycation end-products) and is implicated in aging and disease. MG is assayed by derivatization by 1,2-diaminobenzene derivatives in cell extracts. Such assays are not applicable to high sample throughput, subcellular, live-cell and in vivo estimations. The use of fluorogenic probes designed for NO (nitric oxide) detection in biological samples and living cells has inadvertently provided probes for the detection of dicarbonyls such as MG. We describe the application of DAF-2 (4,5-diaminofluorescein) and DAR-1 (4,5-diaminorhodamine) for the detection of MG in cell-free systems and application for high-throughput assay of glyoxalase activity and assay of glucose degradation products in peritoneal dialysis fluids. DAF-2 and DAR-1, as for related BODIPY probes, do not have sufficient sensitivity to detect MG in live cells. Care will also be required to control for NO and dehydroascorbate co-detection and interference from peroxidase catalysing the degradation of probes to MG and glyoxal. Fluorogenic detection of MG, however, has great potential to facilitate the assay of MG and to advance towards that capability of imaging this product in live cells in vitro and small animals in vivo.
Prediction of power fluctuation classes for photovoltaic installations and potential benefits of dynamic reserve allocation
Authors: Nijhuis Michiel , Rawn Barry , Gibescu Madeleine
Published: March 2014

During partly cloudy conditions, the power delivered by a photovoltaic array can easily fluctuate by three quarters of its rated power in 10 s. Fluctuations from photovoltaics of this size and on this time scale may necessitate adding an additional component to power system secondary and primary reserves to regulate frequency. This study quantifies the benefit of dynamically sizing a reserve component to cover photovoltaic fluctuations so that the additional reserves are different for each hour. The concept of categorising an hour as belonging to one of three possible fluctuation classes is presented. Based on historical array data and weather forecast information, several methods of forecasting these classes are evaluated, including persistence, Markov chains and a neural network. A practical tool based on class forecasting is proposed to aid in estimating a photovoltaic reserve requirement ahead of time for horizons ranging from 1 to 24 h. Results indicate that of a 10% possible reduction in total reserves held, most of this benefit (8%) can be obtained for hour‐ahead scheduling with persistence forecasting and that a similar benefit may be possible for four‐hour ahead scheduling if neural networks based on weather forecast information are introduced.
Managing the Frontal Sinus in the Endoscopic Age: Has the Endoscope Changed the Algorithm?
Authors: Kellman Robert , Goyal Parul
Published: March 2014

Management of fractures involving the frontal sinus seems to be more complex than merely obtaining an ideal reduction of the bony injuries. Multiple articles on the management of these fractures suggest that a great deal of controversy persists despite many years of surgical experience. The question posed in this article is whether or not the advent of endoscopic approaches has changed or should change the approaches/algorithms used in the management of these challenging fractures. It is the conclusion of these authors that endoscopic techniques can indeed allow us to change the algorithm for management of frontal sinus trauma. New algorithms are proposed that should provide guidance to craniomaxillofacial surgeons treating these injuries in the endoscopic age.
Linear-response time-dependent density-functional theory with pairing fields
Authors: Peng Degao , van Aggelen Helen , Yang Yang , Yang Weitao
Published: March 2014

Recent development in particle-particle random phase approximation (pp-RPA) broadens the perspective on ground state correlation energies [H. van Aggelen, Y. Yang, and W. Yang, Phys. Rev. A 88, 030501 (2013), Y. Yang, H. van Aggelen, S. N. Steinmann, D. Peng, and W. Yang, J. Chem. Phys. 139, 174110 (2013); D. Peng, S. N. Steinmann, H. van Aggelen, and W. Yang, J. Chem. Phys. 139, 104112 (2013)] and N ± 2 excitation energies [Y. Yang, H. van Aggelen, and W. Yang, J. Chem. Phys. 139, 224105 (2013)]. So far Hartree-Fock and approximated density-functional orbitals have been utilized to evaluate the pp-RPA equation. In this paper, to further explore the fundamentals and the potential use of pairing matrix dependent functionals, we present the linear-response time-dependent density-functional theory with pairing fields with both adiabatic and frequency-dependent kernels. This theory is related to the density-functional theory and time-dependent density-functional theory for superconductors, but is applied to normal non-superconducting systems for our purpose. Due to the lack of the proof of the one-to-one mapping between the pairing matrix and the pairing field for time-dependent systems, the linear-response theory is established based on the representability assumption of the pairing matrix. The linear response theory justifies the use of approximated density-functionals in the pp-RPA equation. This work sets the fundamentals for future density-functional development to enhance the description of ground state correlation energies and N ± 2 excitation energies.
A thermal control system for long-term survival of scientific instruments on lunar surface
Authors: Ogawa K. , Iijima Y. , Sakatani N. , Otake H. , Tanaka S.
Published: March 2014

A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime −200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a “regolith mound”. Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system.
Fabrication of two-dimensional ferrofluid microdroplet lattices in a microfluidic channel
Authors: Lee Chiun-Peng , Lan Ting-Sheng , Lai Mei-Feng
Published: March 2014

In this paper, we investigated the influences of magnetic field on the ferrofluid droplet generation and the arrangement of the collected droplets in a T-junction microfluidic. Our study includes the field-dependent droplet generation rate, droplet size, as well as the spatial density of the self-assembled droplet collections that were analyzed under the conditions of constant fluid flow rates and capillary number, and all of the field-dependent properties were found inversely proportional to the applied magnetic field strength. In addition, the droplet merging was also able to be avoided by the induced repulsive magnetic force between ferrofluid droplets.
Doubly self-consistent field theory of grafted polymers under simple shear in steady state
Authors: Suo Tongchuan , Whitmore Mark D.
Published: March 2014

We present a generalization of the numerical self-consistent mean-field theory of polymers to the case of grafted polymers under simple shear. The general theoretical framework is presented, and then applied to three different chain models: rods, Gaussian chains, and finitely extensible nonlinear elastic (FENE) chains. The approach is self-consistent at two levels. First, for any flow field, the polymer density profile and effective potential are calculated self-consistently in a manner similar to the usual self-consistent field theory of polymers, except that the calculation is inherently two-dimensional even for a laterally homogeneous system. Second, through the use of a modified Brinkman equation, the flow field and the polymer profile are made self-consistent with respect to each other. For all chain models, we find that reasonable levels of shear cause the chains to tilt, but it has very little effect on the overall thickness of the polymer layer, causing a small decrease for rods, and an increase of no more than a few percent for the Gaussian and FENE chains. Using the FENE model, we also probe the individual bond lengths, bond correlations, and bond angles along the chains, the effects of the shear on them, and the solvent and bonded stress profiles. We find that the approximations needed within the theory for the Brinkman equation affect the bonded stress, but none of the other quantities.
Dynamics of water-alcohol mixtures: Insights from nuclear magnetic resonance, broadband dielectric spectroscopy, and triplet solvation dynamics
Authors: Sauer D. , Schuster B. , Rosenstihl M. , Schneider S. , Talluto V. , Walther T. , Blochowicz T. , Stühn B. , Vogel M.
Published: March 2014

We combine 2H nuclear magnetic resonance (NMR), broadband dielectric spectroscopy (BDS), and triplet solvation dynamics (TSD) to investigate molecular dynamics in glass-forming mixtures of water and propylene glycol in very broad time and temperature ranges. All methods yield consistent results for the α process of the studied mixtures, which hardly depends on the composition and shows Vogel-Fulcher temperature dependence as well as Cole-Davidson spectral shape. The good agreement between BDS and TDS data reveals that preferential solvation of dye molecules in microheterogeneous mixtures does not play an important role. Below the glass transition temperature Tg, NMR and BDS studies reveal that the β process of the mixtures shows correlation times, which depend on the water concentration, but exhibit a common temperature dependence, obeying an Arrhenius law with an activation energy of Ea = 0.54  eV, as previously reported for mixtures of water with various molecular species. Detailed comparison of NMR and BDS correlation functions for the β process unravels that the former decay faster and more stretched than the latter. Moreover, the present NMR data imply that propylene glycol participates in the β process and, hence, it is not a pure water process, and that the mechanism for molecular dynamics underlying the β process differs in mixtures of water with small and large molecules.
Folding and self-assembly of a small heterotetramer
Authors: Yaşar Fatih , Sieradzan Adam K. , Hansmann Ulrich H. E.
Published: March 2014

Designed miniproteins offer a possibility to study folding and association of protein complexes, both experimentally and in silico. Using replica exchange molecular dynamics and the coarse-grain UNRES force field, we have simulated the folding and self-assembly of the heterotetramer BBAThet1, comparing it with that of the homotetramer BBAT1 which has the same size and ββα-fold. For both proteins, association of the tetramer precedes and facilitates folding of the individual chains.
CdCl2 treatment related diffusion phenomena in Cd1−xZnxS/CdTe solar cells
Authors: Kartopu G. , Taylor A. A. , Clayton A. J. , Barrioz V. , Lamb D. A. , Irvine S. J. C.
Published: March 2014

Utilisation of wide bandgap Cd1−xZnxS alloys as an alternative to the CdS window layer is an attractive route to enhance the performance of CdTe thin film solar cells. For successful implementation, however, it is vital to control the composition and properties of Cd1−xZnxS through device fabrication processes involving the relatively high-temperature CdTe deposition and CdCl2 activation steps. In this study, cross-sectional scanning transmission electron microscopy and depth profiling methods were employed to investigate chemical and structural changes in CdTe/Cd1−xZnxS/CdS superstrate device structures deposited on an ITO/boro-aluminosilicate substrate. Comparison of three devices in different states of completion—fully processed (CdCl2 activated), annealed only (without CdCl2 activation), and a control (without CdCl2 activation or anneal)—revealed cation diffusion phenomena within the window layer, their effects closely coupled to the CdCl2 treatment. As a result, the initial Cd1−xZnxS/CdS bilayer structure was observed to unify into a single Cd1−xZnxS layer with an increased Cd/Zn atomic ratio; these changes defining the properties and performance of the Cd1−xZnxS/CdTe device.