bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiative Hydrodynamic Simulations of He I 10830 Å
Authors: Cheng J. X. , Ding M. D. , Fang C.
Published: July 2013

We study the properties of the He I 10830 Å line under the bombardment of nonthermal electron beam. Using radiative hydrodynamics method, we obtain the line profiles from different model atmospheres by varying the electron beam fluxes. Below a certain electron flux, the spectra become much more absorptions as nonthemal flux increases. Above the threshold, the spectral intensities increase as the flux goes up. We also investigate the temporal evolution of the spectra under the nonthermal heating. For weak electron flux, the profiles evolve from weak absorptions to strong absorptions. For strong nonthermal heating, the profiles can be significantly changed from absorptions to emissions. The spectra also show red or blue asymmetries.
A statistical study on solar soft X-ray flare and the sources
Authors: Guo Juan
Published: July 2013

We surveyed 28 year of Solar X-ray flares and sunspot group records supplied by the National Geophysical Data Center (NGDC) to study the dependence of different class Xray flares on the magnetic structure of sunspot groups statistically. It is found that 82.5% X-class flare, 51.4% M-class flare, 26.3% C-class flare, and 10.1% B-class flare occurred in the sunspot group with βγδ structure. There are 6.6% X-class flares, 17.5% M-class flare, 39.1% C-class flare, and 60.4% B-class flare occurred out of sunspot group.
Tests and applications of nonlinear force-free field extrapolations in spherical geometry
Authors: Guo Y. , Ding M. D.
Published: July 2013

We test a nonlinear force-free field (NLFFF) optimization code in spherical geometry with an analytical solution from Low and Lou. The potential field source surface (PFSS) model is served as the initial and boundary conditions where observed data are not available. The analytical solution can be well recovered if the boundary and initial conditions are properly handled. Next, we discuss the preprocessing procedure for the noisy bottom boundary data, and find that preprocessing is necessary for NLFFF extrapolations when we use the observed photospheric magnetic field as bottom boundaries. Finally, we apply the NLFFF model to a solar area where four active regions interacting with each other. An M8.7 flare occurred in one active region. NLFFF modeling in spherical geometry simultaneously constructs the small and large scale magnetic field configurations better than the PFSS model does.
A small-scale EUV jet in the quiet Sun region
Authors: Hong Junchao , Jiang Yunchun , Zheng Ruisheng , Bi Yi
Published: July 2013

Solar jets are typical proxies of small-scale magnetic reconnection events in the solar atmosphere. In this paper, we observe a small-scale jet in a solar quiet region, using data from SDO/Atmospheric Imaging Assembly (AIA), Helioseismic and Magnetic Imager (HMI), with supplemental data from STEREO/EUVI. From HMI magnetograms and calculated photospheric flows, we find that the jet is related to the interaction between unipolar network fields and emerging internetwork bipoles at the boundary of a supergranular cell. In AIA extreme-ultraviolet images, the jet actually includes two successive plasma ejections along different directions. The first ejection follows a distorted path which guides plasma into a small filament channel nearby. However, the second one shot straight along another direction that is parallel with extrapolated potential magnetic field lines on the local. According to these observations, we advocate that during the jet eruption new emerging magnetic fields are reconnecting at the edge of the supergranular cell with different kinds of ambient fields from low (magnetic canopy) to high (high-reaching loops) to allow the occurrence of successive ejections along different directions.
SDO/AIA and Hinode/EIS observations of interaction between an EUV wave and active region loops
Authors: Yang Liheng , Zhang Jun , Li Ting , Liu Wei
Published: July 2013

We study an EUV wave initiated in active region (AR) 11261 on 2011 August 4 by using the SDO/AIA and the Hinode/EIS. We found that: (1) the EUV wave interacted with AR loops between AR 11261 and AR 11263, and exited mass flows in these loops. (2) EIS observations of AR loops in AR 11263 revealed that at the time of the wave transit, the original red-shifted feature had an increase of about 3 km s−1, and the original blue-shifted feature slightly weakened. These findings could be explained in the framework of a fast-mode magnetosonic wave interpretation for EUV waves.
Accuracy analysis and application of extrapolation of force-free fields in solar active and quiet regions
Authors: Liu Suo , Zhang Hongqi , Su Jiangtao , Song Mutao
Published: July 2013

In this paper, the availability, applicability and deviation of nonlinear force-free (NLFF) fields extrapolated by Approximate Vertical Integration (AVI), Boundary Integral Equation (BIE) and Optimization (Opt.) methods are studied based on the comparison with two semi-analytical fields (Low & Lou 1990). These NLFF extrapolations based on the observational vector magnetograms are used to study the spatial magnetic field in the quiet Sun.
Solar flares observed simultaneously with SphinX, GOES and RHESSI
Authors: Mrozek Tomasz , Gburek Szymon , Siarkowski Marek , Sylwester Barbara , Sylwester Janusz , Kępa Anna , Gryciuk Magdalena
Published: July 2013

In February 2009, during recent deepest solar minimum, Polish Solar Photometer in X-rays (SphinX) begun observations of the Sun in the energy range of 1.2–15 keV. SphinX was almost 100 times more sensitive than GOES X-ray Sensors. The silicon PIN diode detectors used in the experiment were carefully calibrated on the ground using Synchrotron Radiation Source BESSY II. The SphinX energy range overlaps with the Ramaty High Energy Solar Spectroscopic Imager (RHESSI) energy range. The instrument provided us with observations of hundreds of very small flares and X-ray brightenings. We have chosen a group of solar flares observed simultaneously with GOES, SphinX and RHESSI and performed spectroscopic analysis of observations wherever possible. The analysis of thermal part of the spectra showed that SphinX is a very sensitive complementary observatory for RHESSI and GOES.
Flares and non-potentiality of AR 11158
Authors: Song Qiao , Zhang Jun , Yang Shuhong , Liu Yang
Published: July 2013

Five non-potential parameters are calculated to investigate the temporal and spatial variations of vector magnetic field in active region 11158. An area that had evident changes of the azimuth of the vector magnetic field was found. The sunspot rotation may lead to an increase of the non-potentiality. Rapid and prominent increases are found in the variations of unsigned helicity.
Numerical simulations of the CME on 2010 April 8
Authors: Su Yingna , Kliem Bernhard , van Ballegooijen Adriaan , Deluca Edward
Published: July 2013

We present 3D zero-beta ideal MHD simulations of the solar flare/CME event that occurred in Active Region 11060 on 2010 April 8. The initial magnetic configurations of the two simulations are stable nonlinear force-free field and unstable magnetic field models constructed by Su et al. (2011) using the flux rope insertion method. The MHD simulations confirm that the stable model relaxes to a stable equilibrium, while the unstable model erupts as a CME. Comparisons between observations and MHD simulations of the CME are also presented.
Simulation of a CME-driven shock by anisotropic scattering angular distributions
Authors: Wang Xin , Yan Yi-Hua
Published: July 2013

Observations of the interplanetary shock provide us with strong evidences of particle acceleration to multi-MeV protons in a coronal mass ejection (CME). Diffusive shock acceleration (DSA) is an efficient mechanism for cosmic ray (CR). This work presents a dynamical Monte Carlo simulation of a CME-driven shock on 14-Dec-2006 by using a series of Gaussian scattering angular distributions. With the simulated results, we find that particle energy spectrum is affected by energy injection processes under the anisotropic scattering law.
Formation and disappearance of a filament
Authors: Zhou G. P. , Wang J. X. , Tsuneta S.
Published: July 2013

A continuous observations near an small active region (AR) NOAA 10976 by the Solar Optical Telescope (SOT) and X-Ray Telescope (XRT) on board the Hinode satellite during Dec. 02 2007 from 15:50 UT to 19:59 UT. We observed that: (a) the filament formed by merging parallel fibrils into a twist structure. (b) the filament faded by reconnecting among its own loop structures, or being stripped into pieces.These process are always preceded by the brightening. (c) for the disappearance of the filament, it has close correlation with the activity, like untwisting or expanding, of its corresponding X-ray bright rope.
Waldmeier relations and the solar cycle dynamics by the mean-field dynamos
Authors: Pipin V. V. , Sokoloff D. D. , Usoskin I. G.
Published: July 2013

The long-term variability of the sunspot cycle, as recorded by the Wolf numbers, are imprinted in different kinds of statistical relations which relate the cycle amplitudes, duration and shapes. This subject always gets a special attention because it is important for the solar activity forecast. We discuss statistical properties of the mean-field dynamo model with the fluctuating α-effect. Also, we estimate dynamical properties of the model for the long and short time-scale and compare it with the dynamics of the sunspot numbers data sets.
Maternal vitamin D deficiency programmes adult renal renin gene expression and renal function
Authors: Boyce A. C. , Palmer-Aronsten B. J. , Kim M. Y. , Gibson K. J.
Published: July 2013

Renin is essential for renal development and in adult kidneys vitamin D deficiency increases renin gene expression. We aimed to determine whether maternal vitamin D deficiency upregulates fetal renal renin expression, and if this is sustained. We also examined growth and the long-term renal effects in offspring on a normal diet. Female Sprague–Dawley rats in UVB-free housing were fed either vitamin D deficient chow (DEF) or normal chow from 4 weeks and mated with vitamin D replete males at 10 weeks. Fetuses were collected at E20 or dams littered and the pups were weaned onto normal chow. Kidney mRNA levels for renin, (pro)renin receptor [(P)RR], transforming growth factor β 1 (TGF-β1), and nephrin were determined in E20 fetuses and in male offspring at 38 weeks. Renal function was assessed at 33 weeks (24 h, metabolic cage) in both sexes. Renal mRNA expression was upregulated for renin in fetuses (P< 0.05) and was almost doubled in adult male offspring from DEF dams (P< 0.05). Adult males had reduced creatinine clearance, solute excretion and a suppressed urinary sodium-to-potassium ratio (P< 0.05). Female adult DEF offspring drank more and excreted more urine (P< 0.05) but creatinine clearance was not impaired. We conclude that maternal vitamin D depletion upregulates fetal renal renin gene expression and this persists into adulthood where, in males only, there is evidence of sodium retention and compromised renal function. Importantly these effects occurred despite the animals being on a normal diet from the time of weaning onwards.
Shame, perceived knowledge and satisfaction associated with mental health as predictors of attitude patterns towards help-seeking
Authors: Rüsch N. , Müller M. , Ajdacic-Gross V. , Rodgers S. , Corrigan P.W. , Rössler W.
Published: July 2013

Aims.

To examine stigma- and knowledge-related barriers to help-seeking among members of the general population.

Methods.

In a representative survey of young to middle-aged Swiss adults (n = 8875), shame about a potential own mental illness, perceived knowledge about and satisfaction with one's mental health, psychiatric symptoms and attitudes towards help-seeking were assessed.

Results.

A latent profile analysis of all participants yielded two groups with different attitudes towards help-seeking. Relative to the majority, a one-in-four subgroup endorsed more negative attitudes towards seeking professional help, including psychiatric medication, and was characterized by more shame, less perceived knowledge, higher satisfaction with their mental health, younger age, male gender and lower education. Among participants with high symptom levels (n = 855), a third subgroup was reluctant to seek help in their private environment and characterized by high symptoms as well as low satisfaction with their mental health.

Conclusions.

Shame as an emotional proxy of self-stigma as well as poor subjective mental health literacy may be independent barriers to help-seeking. Interventions to increase mental health service use could focus on both variables and on those individuals with more negative views about professional help, in the general public as well as among people with a current mental illness.
Meta-analysis of IDH-mutant cancers identifies EBF1 as an interaction partner for TET2
Authors: Guilhamon Paul , Eskandarpour Malihe , Halai Dina , Wilson Gareth A. , Feber Andrew , Teschendorff Andrew E. , Gomez Valenti , Hergovich Alexander , Tirabosco Roberto , Fernanda Amary M. , Baumhoer Daniel , Jundt Gernot , Ross Mark T. , Flanagan Adrienne M. , Beck Stephan
Published: July 2013

Isocitrate dehydrogenase (IDH) genes 1 and 2 are frequently mutated in acute myeloid leukaemia (AML), low-grade glioma, cholangiocarcinoma (CC) and chondrosarcoma (CS). For AML, low-grade glioma and CC, mutant IDH status is associated with a DNA hypermethylation phenotype, implicating altered epigenome dynamics in the aetiology of these cancers. Here we show that the IDH variants in CS are also associated with a hypermethylation phenotype and display increased production of the oncometabolite 2-hydroxyglutarate, supporting the role of mutant IDH-produced 2-hydroxyglutarate as an inhibitor of TET-mediated DNA demethylation. Meta-analysis of the acute myeloid leukaemia, low-grade glioma, cholangiocarcinoma and CS methylation data identifies cancer-specific effectors within the retinoic acid receptor activation pathway among the hypermethylated targets. By analysing sequence motifs surrounding hypermethylated sites across the four cancer types, and using chromatin immunoprecipitation and western blotting, we identify the transcription factor EBF1 (early B-cell factor 1) as an interaction partner for TET2, suggesting a sequence-specific mechanism for regulating DNA methylation.
Mild Cognitive Impairment
Authors: Ward Roberta J.
Published: July 2013

As the aging population throughout the World steadily increases, within the next two decades cognitive dysfunction will emerge as a major clinical and economic problem. Its diagnosis is becoming progressively easier by the use of a wide range of cognitive tests. However, once diagnosed it is apparent that therapeutic intervention is still not possible, with the underlying disease process either remaining static or progressing to Alzheimer’s disease.
The Role of Metals in Alzheimer’s Disease
Authors: Hajji Nabil , Calvert Carly , Ritchie Craig W. , Sastre Magdalena
Published: July 2013

Alzheimer’s disease (AD) is the most common cause of dementia and the main pathological feature is massive neuronal loss in areas of the brain responsible for memory and learning, such as the cortex and hippocampus. In the brain, three major hallmarks are associated with the processes of this disease: amyloid beta peptide (Aβ) deposition, neurofibrillary tangles (NFTs) of hyperphosphorylated microtubule‐associated tau and synaptic loss. Epidemiological studies have shown an association between heavy metals, such as lead, cadmium and mercury, and AD. While these metals have no biological function with the pathogenesis of AD, others such as iron, copper or zinc fulfil various essential biological functions where any changes in their levels by excess or deficit can lead to deleterious responses and alter cognitive functions.
Friedreich’s Ataxia
Authors: Pastore Annalisa
Published: July 2013

Friedreich’s ataxia is a rare but relentless neurodegenerative disease which affects one individual in 50 000. Being recessive, this hereditary condition is carried by one individual in ca. 120. Although it was first diagnosed in 1863 by Nikolaus Friedreich, it was only in 1996 that the genetic cause became clear: it is due to anomalous expansion of a nucleotide triplet in the first exon of the FRDA gene, which leads to partial silencing of the frataxin protein. When these findings were first published, nothing was known about the cellular localization, evolution and function of frataxin. We now know that frataxin is an essential mitochondrial protein that is highly conserved in most organisms and is implicated in the regulation of iron–sulfur cluster formation. Here, we review the long path that has led us to our current understanding of the molecular causes of this ataxia.
Prion Disease
Authors: Rowinska‐Zyrek Magdalena , Valensin Daniela , Luczkowski Marek , Kozlowski Henryk
Published: July 2013

Prion diseases (derived either from infection, germline mutations or most often occurring sporadically), both in humans and animals, are fatal neurodegenerative disorders characterized by progressive brain degeneration. It is widely accepted that they are caused by protein‐only infectious agents propagating disease by inducing protein conformational changes. The molecular mechanism of prion pathologies is not yet entirely understood but some aspects seem to be generally accepted, such as spongiform degeneration, non‐classical inflammation of the brain, progressive neuron loss, accumulation of protein aggregates and synaptic alterations.
Multiple Sclerosis
Authors: Reynolds Richard , Crichton Robert
Published: July 2013

Neurodegenerative diseases can often affect cognitive function (e.g. MCI, Alzheimer’s disease), motor function (Parkinson’s disease) or various combinations of both. In this chapter we describe multiple sclerosis (MS), the prototype inflammatory autoimmune disorder of the central nervous system, which causes demyelination of the central nervous system, resulting in progressive loss of motor and sensory function.
Elemental Sustainability and the Importance of Scarce Element Recovery
Authors: Hunt Andrew J. , Farmer Thomas J. , Clark James H.
Published: July 2013

A growing movement towards the development of “low carbon technologies” and an increased demand for consumer electronics are contributing towards a resource deficit. Many of these technologies require rare and precious metals for their production and use. The reserves of these elements are being depleted at a rapid rate, but they are not “running out” or being destroyed. These unique elements are being quickly dispersed throughout our environment, making their recapture both highly challenging and costly. As such, it is essential to develop new sustainable routes and strategies for the recovery and reuse of these elements. This chapter discusses the issues relating to those elements regarded as being “critical” in terms of having significant international supply risk issues and which are also vital to a nation’s economy (or company’s business). The importance of adopting a sustainable holistic approach to the extraction, processing, use and recovery is highlighted as being vital in ensuring a sustainable long‐term supply of all elements.
Integration of Traditional Methods for Elemental Recovery in a Zero‐waste Recycling Flow Sheet
Authors: Wang Xuan , Van Gerven Tom , Blanpain Bart
Published: July 2013

The traditional extractive methods for steel, aluminum, copper, zinc and lead, which are some of the basic materials used in human activities, are briefly described in this chapter. In a case study of copper slag, these traditional methods of extractive metallurgy are integrated with utilization of the residual material after extraction, in order to design a complete recycling flow sheet.
Ionometallurgy: Processing of Metals using Ionic Liquids
Authors: Abbott Andrew P. , Frisch Gero
Published: July 2013

The technological world is heavily reliant upon a wide range of metals, many of which are produced in high temperature, energy intensive processes (pyrometallurgy or molten salt electrometallurgy). The current energy efficient alternatives (hydrometallurgy) simply transfer the problem by using aggressive or toxic reagents in aqueous solution. In the environment, metals are becoming rarer and some are predicted soon to become “extinct”. Metal recycling and urban mining are therefore increasingly important. Ionometallurgy, metal processing in ambient temperature ionic fluids, offers the prospect of purifying metals from a range of sources at ambient condition whilst minimising emission of hazardous reagents to the environment. Concentrating metals in solution optimises energy efficiency and promises unprecedented selectivity in metal purification. Ionometallurgy aims to develop socially responsible and efficient methods of obtaining metals from complex mixtures such as ores, electronic waste and spent nuclear fuels.
Biosorption of Elements
Authors: Pei Gan Pei , Yau Li Sam Fong
Published: July 2013

Biosorption is a unique ability of living or dead biomass to interact with substances such as metals where reduction of sorbate concentration can be achieved. Thus, it has been widely proposed as a promising alternative for metal remediation and recovery owing to its low cost and sustainable “green” nature. Despite considerable biosorption‐related research performed in the past few decades, no significant commercial success has been achieved so far. This chapter starts with discussion of the basic science of biosorption and the potential of some selected biomasses such as yeast, algae, agro‐based waste and vermicompost to be used as biosorbent material. Following this, some important issues regarding the practical application of biosorption are highlighted, including the advantages and disadvantages of using dead or living biomass, the availability of biosorption reactors, immobilization techniques, metal recovery and post‐treatment of spent biosorbent. Lastly, current challenges that limit the commercial success of biosorption as well as the direction of future research are discussed.
Hyperaccumulation by Plants
Authors: Anderson Christopher W. N.
Published: July 2013

Society has long recognised that certain plant species can infer the existence of minerals in the underlying soil but only in the later years of the 20th century was the ability of some plants to accumulate heavy metals reliably quantified. The term hyperaccumulation was introduced to describe such plants. Of the many metals that can be hyperaccumulated, two of the more interesting are nickel and gold. Nickel is naturally hyperaccumulated by around 450 plant species, while plants can be forced to accumulate gold if the metal is made soluble in the soil (induced hyperaccumulation). The phytoextraction of metal from low‐grade ore, waste rock or contaminated soil represents a remediation technique, or in some cases an economically viable option for metal recovery. In some scenarios, the recovery of gold from a crop of plants can provide revenue for the remediation of more toxic metals from contaminated soil. In another, nickel farming may be an alternative livelihood for communities growing food on poor‐yielding metalliferous soils. As society progresses through the 21st century, the sustainability of the metals extractive industry must be improved. Hyperaccumulation will never replace conventional mining but it is a physiological trait that can be used for sustainable development. There are opportunities for ‘green technologies’ to support phytoextraction by better biomass processing and the realisation of specific applications for metal accumulated by plants.
Mining Municipal Waste: Prospective for Elemental Recovery
Authors: Dodson J. , Parker H. L.
Published: July 2013

Waste is an ever‐increasing challenge in all corners of the globe as populations and material consumption increase. At the same time, global consumption of metals is predicted to increase five times by 2050, with industrialised nations currently using 5–10 times more than developing countries. Unless ways are found to value ‘waste’ and create a ‘closed loop’ materials economy there is little chance of achieving elemental sustainability or equitable distribution of resources. This chapter explores the challenges and opportunities for mining municipal waste with an emphasis on metals and particularly precious and speciality elements. Current elemental stocks contained in society and how they flow into waste are discussed as well as the technological and social difficulties of accessing these stockpiles. The potential for urban mining from areas such as landfill and waste incineration ash are considered along with analysis of techniques for retrieving elements from these sources. A current example of urban mining in action, through the retrieval of Pd and Pt from road sweepings, demonstrates the potential of previously considered ‘waste’ as an elemental feedstock.
Small nuclear RNAs and mRNAs: linking RNA processing and transport to spinal muscular atrophy
Authors: Sleeman Judith
Published: July 2013

The splicing of pre-mRNA by the spliceosome is a characteristic feature of eukaryotic cells, dependent on a group of snRNPs (small nuclear ribonucleoproteins). These splicing snRNPs have a complex assembly pathway involving multiple steps that take place in different regions of the cell, which is reflected in their complex subcellular distribution. Vital to the assembly of splicing snRNPs is the protein SMN (survival of motor neurons). In multicellular organisms, SMN acts in the cytoplasm, together with its associated protein complex to assemble a heptameric ring of proteins called the Sm proteins as an early stage in splicing snRNP assembly. A deficiency of the SMN protein results in the inherited neurodegenerative condition SMA (spinal muscular atrophy), a leading cause of infant mortality specifically affecting spinal motor neurons. It has long been a puzzle how lowered levels of a protein required for a process as fundamental as splicing snRNP assembly can result in a condition with such a definite cell-type-specificity. The present review highlights recent research that points to wider roles in RNA metabolism for both SMN itself and the Sm proteins with which it is linked.
Discovery of novel small RNAs in the quest to unravel genome complexity
Authors: Hall Adam E. , Dalmay Tamas
Published: July 2013

The different RNA populations within the cell, or the ‘RNAome’, form a complex and integral layer of gene regulation. In particular, small non-coding RNAs such as microRNAs have been shown to regulate as much as half of all genes expressed in mammals. The recent discovery of novel small RNAs derived from tRNAs, snoRNAs and Y RNAs, as well as the development of techniques that can reduce sequencing bias of these molecules, is slowly helping us to unveil the secrets of the genome.
The multifunctional RNase XRN2
Authors: Miki Takashi S. , Großhans Helge
Published: July 2013

Different classes of RNA function in various cellular processes, and their biogenesis and turnover involve diverse RNases for processing and degradation. XRN2 is a 5′→3′ exoribonuclease that is evolutionarily conserved in eukaryotes. It is predominantly localized in the nucleus and recognizes single-stranded RNA with a 5′-terminal monophosphate to degrade it processively to mononucleotides. In the present paper, we review functions of XRN2 and its cofactors in maturation, surveillance and activity control of several classes of RNA such as pre-mRNA (precursor mRNA), rRNA and snoRNA (small nucleolar RNA).
New insights into the structure and function of the pseudokinase domain in JAK2
Authors: Silvennoinen Olli , Ungureanu Daniela , Niranjan Yashavanthi , Hammaren Henrik , Bandaranayake Rajintha , Hubbard Stevan R.
Published: July 2013

JAK (Janus kinase) 2 plays a critical role in signal transduction through several cytokine receptors. JAKs contain a typical tyrosine kinase domain preceded by a pseudokinase [JH2 (JAK homology 2)] domain which has been considered to be catalytically inactive. Identification of activating mutations in the JH2 domain of JAK2 as the major cause for polycythaemia vera and other MPNs (myeloproliferative neoplasms) demonstrate the critical regulatory function for this domain, but the underlying mechanisms have remained elusive. We have performed biochemical and functional analysis on the JH2 domain of JAK2. The results indicate that JH2 functions as an active protein kinase and phosphorylates two residues in JAK2 (Ser523 and Tyr570) that have been shown previously to be negative regulatory sites for JAK2 activity. The crystal structure of the JAK2 JH2 domain provides an explanation for the functional findings and shows that JH2 adopts a prototypical kinase fold, but binds MgATP through a non-canonical mode. The structure of the most prevalent pathogenic JH2 mutation V617F shows a high level of similarity to wild-type JH2. The most notable structural deviation is observed in the N-lobe αC-helix. The structural and biochemical data together with MD (molecular dynamics) simulations show that the V617F mutation rigidifies the αC-helix, which results in hyperactivation of the JH1 domain through an as yet unidentified mechanism. These results provide structural and functional insights into the normal and pathogenic function of the JH2 domain of JAK2.
The primary target of let-7 microRNA
Authors: Pasquinelli Amy E.
Published: July 2013

The let-7 miRNA (microRNA) is an essential regulator of development from nematode worms to humans. Altered expression of let-7 results in larval arrest or lethality in Caenorhabditis elegans. Likewise, under- or over-expression of let-7 in human cells can result in cellular overproliferation or halted cell division respectively. Thus the biogenesis of this critical miRNA is controlled at multiple levels. An unexpected mechanism for regulating the initial processing of let-7 was recently found to involve the let-7 miRNA itself. The mature let-7 miRNA along with its effector protein, Argonaute, were shown to bind to a site in the primary transcripts produced by the let-7 gene. This interaction enhances processing through a novel auto-regulatory feedback loop. This discovery highlights a new role for the miRNA complex in regulating miRNA biogenesis and enriches the classes of RNAs targeted by Argonaute.
mTORC1 regulates the efficiency and cellular capacity for protein synthesis
Authors: Proud Christopher G.
Published: July 2013

mTORC1 (mammalian target of rapamycin complex 1) is activated by nutrients, growth factors and certain hormones. Signalling downstream of mTORC1 promotes protein synthesis by both activating the processes of translation initiation and elongation, in the short term, and the production of new ribosomes, in the longer term. mTORC1 signalling stimulates the translation of the mRNAs encoding the ribosomal proteins, activates RNA polymerases I and III, which make the rRNAs, and promotes the processing of the precursor for the main rRNAs. Taken together, these effects allow mTORC1 signalling to drive cell growth and proliferation.
Rheb and Rags come together at the lysosome to activate mTORC1
Authors: Groenewoud Marlous J. , Zwartkruis Fried J.T.
Published: July 2013

mTORC1 (mammalian target of rampamycin complex 1) is a highly conserved protein complex regulating cell growth and metabolism via its kinase mTOR (mammalian target of rapamycin). The activity of mTOR is under the control of various GTPases, of which Rheb and the Rags play a central role. The presence of amino acids is a strict requirement for mTORC1 activity. The heterodimeric Rag GTPases localize mTORC1 to lysosomes by their amino-acid-dependent interaction with the lysosomal Ragulator complex. Rheb is also thought to reside on lysosomes to activate mTORC1. Rheb is responsive to growth factors, but, in conjunction with PLD1 (phospholipase D1), is also an integral part of the machinery that stimulates mTORC1 in response to amino acids. In the present article, we provide a brief overview of novel mechanisms by which amino acids affect the function of Rags. On the basis of existing literature, we postulate that Rheb is activated at the Golgi from where it will travel to lysosomes. Maturation of endosomes into lysosomes may be required to assure a continuous supply of GTP-bound Rheb for mTORC1 activation, which may help to drive the maturation process.
The structural mechanisms that underpin mitotic kinase activation
Authors: Dodson Charlotte A. , Haq Tamanna , Yeoh Sharon , Fry Andrew M. , Bayliss Richard
Published: July 2013

In eukaryotic cells, the peak of protein phosphorylation occurs during mitosis, switching the activities of a significant proportion of proteins and orchestrating a wholesale reorganization of cell shape and internal architecture. Most mitotic protein phosphorylation events are catalysed by a small subset of serine/threonine protein kinases. These include members of the Cdk (cyclin-dependent kinase), Plk (Polo-like kinase), Aurora, Nek (NimA-related kinase) and Bub families, as well as Haspin, Greatwall and Mps1/TTK. There has been steady progress in resolving the structural mechanisms that regulate the catalytic activities of these mitotic kinases. From structural and biochemical perspectives, kinase activation appears not as a binary process (from inactive to active), but as a series of states that exhibit varying degrees of activity. In its lowest activity state, a mitotic kinase may exhibit diverse autoinhibited or inactive conformations. Kinase activation proceeds via phosphorylation and/or association with a binding partner. These remodel the structure into an active conformation that is common to almost all protein kinases. However, all mitotic kinases of known structure have divergent features, many of which are key to understanding their specific regulatory mechanisms. Finally, mitotic kinases are an important class of drug target, and their structural characterization has facilitated the rational design of chemical inhibitors.
Prospects for stable analogues of phosphohistidine
Authors: McAllister Tom E. , Hollins Jeffrey J. , Webb Michael E.
Published: July 2013

Phosphorylation is a ubiquitous protein post-translational modification, and the importance of phosphorylation of serine, threonine and tyrosine is well established. What is lesser known is that almost all heteroatom-containing amino acids can be phosphorylated and, among these, histidine, aspartate and cysteine have well established roles in bacterial signalling pathways. The first of these, phosphohistidine, is the most unusual in that it is labile under many conditions used to study proteins in vitro and can exist as two different isomers. In the present short review, we highlight the chemical challenges that this modification presents and the manner in which chemical synthesis has been used to identify and mimic the modification in proteins.
Receptor tyrosine kinases with intracellular pseudokinase domains
Authors: Mendrola Jeannine M. , Shi Fumin , Park Jin H. , Lemmon Mark A.
Published: July 2013

As with other groups of protein kinases, approximately 10% of the RTKs (receptor tyrosine kinases) in the human proteome contain intracellular pseudokinases that lack one or more conserved catalytically important residues. These include ErbB3, a member of the EGFR (epidermal growth factor receptor) family, and a series of unconventional Wnt receptors. We showed previously that, despite its reputation as a pseudokinase, the ErbB3 TKD (tyrosine kinase domain) does retain significant, albeit weak, kinase activity. This led us to suggest that a subgroup of RTKs may be able to signal even with very inefficient kinases. Recent work suggests that this is not the case, however. Other pseudokinase RTKs have not revealed significant kinase activity, and mutations that impair ErbB3′s weak kinase activity have not so far been found to exhibit signalling defects. These findings therefore point to models in which the TKDs of pseudokinase RTKs participate in receptor signalling by allosterically regulating associated kinases (such as ErbB3 regulation of ErbB2) and/or function as regulated ‘scaffolds’ for other intermolecular interactions central to signal propagation. Further structural and functional studies, particularly of the pseudokinase RTKs involved in Wnt signalling, are required to shed new light on these intriguing signalling mechanisms.
A pickup in pseudokinase activity
Authors: Dar Arvin C.
Published: July 2013

Kinases catalyse the phosphorylation of target substrates on hydroxy group-containing residues as a means to nucleate multi-component complexes or to stabilize unique conformational states. Through this biochemical activity, kinases play critical roles in many signal transduction and disease pathways. Pseudokinases constitute a subclass of these enzymes that were originally predicted as inactive on the basis of mutations of key conserved active-site residues. However, recent biochemical and structural analyses have revealed several enzymatically active pseudokinases, suggesting either that novel mechanisms of phosphorylation are at play or that the constraints for highly conserved active-site residues are looser than originally anticipated. The purpose of the present review is to summarize several of the active pseudokinases, and one in particular termed KSR (kinase suppressor of Ras), which was recently found to possess a kinase activity that can become accelerated through an allosteric mechanism. Utilization of catalytic activity or structural features of the kinase fold may be key to the function of many pseudokinases.
Conserved sequence motifs and the structure of the mTOR kinase domain
Authors: Sauer Evelyn , Imseng Stefan , Maier Timm , Hall Michael N.
Published: July 2013

The atypical serine/threonine kinase mTOR (mammalian target of rapamycin) is a central regulator of cell growth and metabolism. mTOR is part of two multisubunit signalling complexes, mTORC1 and mTORC2. Although many aspects of mTOR signalling are understood, the lack of high-resolution structures impairs a detailed understanding of complex assembly, function and regulation. The structure of the kinase domain is of special interest for the development of mTOR inhibitors as anti-cancer agents. A homology model of the mTOR kinase domain was derived from the structure of PI3Ks (phosphoinositide 3-kinases). More recently, the crystal structure of the catalytic domain of human mTOR was determined, providing long-awaited structural insight into the architecture of mTOR. Interestingly, the homology model predicted several aspects of the crystal structure. In the present paper, we revisit the homology model in the context of the now available crystal structure of the mTOR kinase domain.
Dawn of the dead: protein pseudokinases signal new adventures in cell biology
Authors: Eyers Patrick A. , Murphy James M.
Published: July 2013

Recent studies of proteins containing kinase-like domains that lack catalytic residue(s) classically required for phosphotransfer, termed pseudokinases, have uncovered important roles in cell signalling across the kingdoms of life. Additionally, mutations within pseudokinase domains are known to underlie human diseases, suggesting that these proteins may represent new and unexplored therapeutic targets. To date, few pseudokinases have been studied in intricate detail, but as described in the present article and in the subsequent papers in this issue of Biochemical Society Transactions, several new studies have provided an advanced template and an improved framework for interrogating the roles of pseudokinases in signal transduction. In the present article, we review landmarks in the establishment of this field of study, highlight some experimental challenges and propose a simple scheme for definition of these domains based on their primary sequences, rather than experimentally defined nucleotide-binding or catalytic activities.
Pseudokinases from a structural perspective
Authors: Taylor Susan S. , Shaw Andrey , Hu Jiancheng , Meharena Hiruy S. , Kornev Alexandr
Published: July 2013

The catalytic (C) subunit of PKA was the first protein kinase structure to be solved, and it continues to serve as the prototype for the protein kinase superfamily. In contrast, by comparing many active and inactive kinases, we developed a novel ‘spine’ concept where every active kinase is composed of two hydrophobic spines anchored to a hydrophobic F-helix. The R-spine (regulatory spine) is dynamically assembled, typically by activation loop phosphorylation, whereas the C-spine (catalytic spine) is completed by the adenine ring of ATP. In the present paper, we show how the spine concept can be applied to B-Raf, specifically to engineer a kinase-dead pseudokinase. To achieve this, we mutated one of the C-spine residues in the N-lobe (N-terminal lobe), Ala481, to phenylalanine. This mutant cannot bind ATP and is thus kinase-dead, presumably because the phenylalanine ring fills the adenine-binding pocket. The C-spine is thus fused. However, the A481F mutant is still capable of binding wild-type B-Raf and wild-type C-Raf, and dimerization with a wild-type Raf leads to downstream activation of MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] and ERK. The mutant requires dimerization, but is independent of Ras and does not require enzymatic activity. By distinguishing between catalytic and scaffold functions of B-Raf, we define kinases as being bifunctional and show that, at least in some cases, the scaffold function is sufficient for downstream signalling. Since this alanine residue is one of the most highly conserved residues in the kinome, we suggest that this may be a general strategy for engineering kinase-dead pseudokinases and exploring biological functions that are independent of catalysis.
Diagnosis of open‐switch faults in variable speed drives by stator current analysis and pattern recognition
Authors: Campos‐Delgado Daniel Ulises , Pecina‐Sánchez José Angel , Espinoza‐Trejo Diego Rivelino , Arce‐Santana Edgar Román
Published: July 2013

This study addresses the problem of detection and isolation of open‐switch faults in voltage source inverters by processing the stator current measurements. First, the resulting post‐fault trajectories for the stator currents are analytically derived for single and concurrent faults (21 classes) by using Fourier series. This analysis motivated the proposed approach, which is based on the resulting pattern of the stator currents in the dq‐frame after a fault, where a histogram of the trajectory is calculated by dividing the plane in 24 equally spaced sectors. From the calculated histogram, a distinctive signature is associated to each fault trajectory in the dq‐plane. Single and double faults in the power semi‐conductors are analysed that all provide linearly independent signatures for fault isolation. The proposed isolation methodology is independent of the load torque (system disturbance), supply frequency and only requires the information of the stator currents. Furthermore, since the isolation stage is focused on the angle of the current trajectories in the dq‐plane, open‐ and closed‐loop configurations of a variable speed drive can be simultaneously handled. Experimental results with a test bench of 3/4 HP induction motor under single and concurrent faults validated the proposed methodology.
Line‐start permanent‐magnet motor synchronisation capability improvement using slotted solid rotor
Authors: Niaz Azari Milad , Mirsalim Mojtaba
Published: July 2013

This study presents a line‐start permanent‐magnet motor with high synchronisation capability using a slotted solid rotor. With slotted solid rotors, a much better magnetic flux and current penetration into the rotor is achieved. Moreover with additional magnetic flux penetration into rotor core, the motor slip decreases and electromagnetic torque near synchronous speed will increase. Consequently, the proposed motor can reach synchronous speed under higher load torques and inertias. Two‐dimensional finite‐element method has been implemented in order to confirm this new idea. Finally, a four‐pole, 250 V, 1500 rpm, 1050 W, three‐phase synchronous motor with slotted solid rotor is designed and prototyped to experimentally validate the capabilities of the proposed motor.
Functional thermo-dynamics: A generalization of dynamic density functional theory to non-isothermal situations
Authors: Anero Jesús G. , Español Pep , Tarazona Pedro
Published: July 2013

We present a generalization of Density Functional Theory (DFT) to non-equilibrium non-isothermal situations. By using the original approach set forth by Gibbs in his consideration of Macroscopic Thermodynamics (MT), we consider a Functional Thermo-Dynamics (FTD) description based on the density field and the energy density field. A crucial ingredient of the theory is an entropy functional, which is a concave functional. Therefore, there is a one to one connection between the density and energy fields with the conjugate thermodynamic fields. The connection between the three levels of description (MT, DFT, FTD) is clarified through a bridge theorem that relates the entropy of different levels of description and that constitutes a generalization of Mermin's theorem to arbitrary levels of description whose relevant variables are connected linearly. Although the FTD level of description does not provide any new information about averages and correlations at equilibrium, it is a crucial ingredient for the dynamics in non-equilibrium states. We obtain with the technique of projection operators the set of dynamic equations that describe the evolution of the density and energy density fields from an initial non-equilibrium state towards equilibrium. These equations generalize time dependent density functional theory to non-isothermal situations. We also present an explicit model for the entropy functional for hard spheres.