bluuebunny/crossref_metadata_2025_split huggingface dataset:
Furry promotes acetylation of microtubules in the mitotic spindle by inhibition of SIRT2 tubulin deacetylase
Authors: Nagai Tomoaki , Ikeda Masanori , Chiba Shuhei , Kanno Shin-ichiro , Mizuno Kensaku 
Published: July 2013

Summary
The structure and function of microtubules (MTs) are regulated by post-translational modifications of tubulin subunits, such as acetylation of the Lys40 residue of α-tubulin. Regulation of the organization and dynamics of MTs is essential for the precise formation of the mitotic spindle. Spindle MTs are highly acetylated, but the mechanism regulating this acetylation is largely unknown. Furry (Fry) is an evolutionarily conserved protein that binds to MTs and colocalizes with acetylated MTs in the mitotic spindle. In this study, we examined the role of Fry in the acetylation of MTs in the mitotic spindle. Depletion of Fry significantly reduced the level of MT acetylation in the mitotic spindle. Expression of the N-terminal fragment of Fry induced hyperacetylation of MTs in both mitotic and interphase cells. These results indicate that Fry promotes MT acetylation in the mitotic spindle. We also found that Fry binds to the tubulin deacetylase SIRT2, preferentially in mitotic cells. Cell-free experiments revealed that the N-terminal region of Fry is the domain responsible for binding to and inhibiting the tubulin-deacetylase activity of SIRT2. AGK2, a specific inhibitor of SIRT2, increased the level of MT acetylation in the mitotic spindle, indicating that SIRT2 is involved in the deacetylation of spindle MTs. Furthermore, AGK2 reversed the decrease in MT acetylation induced by Fry depletion. In summary, these results suggest that Fry plays a crucial role in promoting the level of MT acetylation in the mitotic spindle by inhibiting the tubulin-deacetylase activity of SIRT2.
Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization inC. elegans
Authors: Wojtyniak Martin , Brear Andrea G. , O'Halloran Damien M. , Sengupta Piali 
Published: July 2013

SummaryPrimary cilia are ubiquitous sensory organelles that concentrate transmembrane signaling proteins essential for sensing environmental cues. Mislocalization of crucial ciliary signaling proteins, such as the tetrameric cyclic nucleotide-gated (CNG) channels, can lead to cellular dysfunction and disease. Although several cis- and trans-acting factors required for ciliary protein trafficking and localization have been identified, whether these mechanisms act in a protein- and cell-specific manner is largely unknown. Here, we show that CNG channel subunits can be localized to discrete ciliary compartments in individual sensory neurons in C. elegans, suggesting that channel composition is heterogeneous across the cilium. We demonstrate that ciliary localization of CNG channel subunits is interdependent on different channel subunits in specific cells, and identify sequences required for efficient ciliary targeting and localization of the TAX-2 CNGB and TAX-4 CNGA subunits. Using a candidate gene approach, we show that Inversin, transition zone proteins, intraflagellar transport motors and a MYND-domain protein are required to traffic and/or localize CNG channel subunits in both a cell- and channel subunit-specific manner. We further find that TAX-2 and TAX-4 are relatively immobile in specific sensory cilia subcompartments, suggesting that these proteins undergo minimal turnover in these domains in mature cilia. Our results uncover unexpected diversity in the mechanisms that traffic and localize CNG channel subunits to cilia both within and across cell types, highlighting the essential contribution of this process to cellular functions.
Functional replacement of fission yeast γ-tubulin small complex proteins Alp4 and Alp6 by human GCP2 and GCP3
Authors: Riehlman Timothy D. , Olmsted Zachary T. , Branca Carmen N. , Winnie Adam M. , Seo Lan , Cruz Leilani O. , Paluh Janet L. 
Published: July 2013

Summary
Microtubule-organizing centers such as the γ-tubulin ring complex (γ-TuRC) act as a template for polarized growth and regulation of microtubules that are essential for diverse cellular structures and processes in eukaryotes. New structural models of the budding yeast γ-tubulin small complex (γ-TuSC) of the γ-TuRC combined with functional studies done in multiple eukaryotes are revealing the first mechanistic clues into control of microtubule nucleation and organization. Cross-species studies of human and budding yeast γ-TuSC proteins in fission yeast revealed conserved and divergent structural and functional features of the γ-TuSC. We show genetically that GCP3/Spc98 function is fully conserved with Alp6 across species but that functional differences exist between GCP2/Spc97 and Alp4. By further analysis of human γ-TuSC proteins, we found that GCP3 assembles normally into the &gt;2000 kDa fission yeast γ-TuRC and that the GCP3 gene replaces fission yeast alp6. Interestingly, human GCP2 replaces the essential alp4 gene but is unable to rescue a normally recessive G1 defect of the alp4-1891 allele that results in loss of γ-TuRC from poles in subsequent cell cycles. Biochemically, GCP2 incorporation into fission yeast γ-TuRC is limited in the presence of Alp4; instead, the bulk of GCP2 fractionates as smaller complexes. By generating a functional Alp4–GCP2 chimeric protein we determined that the GCP2 N-terminal domain limits its ability to fully displace or compete with Alp4 during γ-TuRC assembly. Our findings have broad importance for understanding the essential domains of γ-TuSC proteins in the γ-TuRC mechanism.
Myo10 is a key regulator of TNT formation in neuronal cells
Authors: Gousset Karine , Marzo Ludovica , Commere Pierre-Henri , Zurzolo Chiara 
Published: July 2013

Summary
Cell-to-cell communication is essential in multicellular organisms. Tunneling nanotubes (TNTs) have emerged as a new type of intercellular spreading mechanism allowing the transport of various signals, organelles and pathogens. Here, we study the role of the unconventional molecular motor myosin-X (Myo10) in the formation of functional TNTs within neuronal CAD cells. Myo10 protein expression increases the number of TNTs and the transfer of vesicles between co-cultured cells. We also show that TNT formation requires both the motor and tail domains of the protein, and identify the F2 lobe of the FERM domain within the Myo10 tail as necessary for TNT formation. Taken together, these results indicate that, in neuronal cells, TNTs can arise from a subset of Myo10-driven dorsal filopodia, independent of its binding to integrins and N-cadherins. In addition our data highlight the existence of different mechanisms for the establishment and regulation of TNTs in neuronal cells and other cell types.
Functional expression of the multimodal extracellular calcium-sensing receptor in pulmonary neuroendocrine cells
Authors: Lembrechts Robrecht , Brouns Inge , Schnorbusch Kathy , Pintelon Isabel , Kemp Paul J. , Timmermans Jean-Pierre , Riccardi Daniela , Adriaensen Dirk 
Published: July 2013

Summary
The Ca2+-sensing receptor (CaSR) is the master regulator of whole-body extracellular free ionized [Ca2+]o. In addition to sensing [Ca2+]o, CaSR integrates inputs from a variety of different physiological stimuli. The CaSR is also expressed in many regions outside the [Ca2+]o homeostatic system, including the fetal lung where it plays a crucial role in lung development. Here, we show that neuroepithelial bodies (NEBs) of the postnatal mouse lung express a functional CaSR. NEBs are densely innervated groups of neuroendocrine epithelial cells in the lung representing complex sensory receptors in the airways and exhibiting stem cell characteristics. qRT-PCR performed on laser microdissected samples from GAD67–GFP mouse lung cryosections revealed exclusive expression of the CaSR in the NEB microenvironment. CaSR immunoreactivity was present at NEB cells from postnatal day 14 onwards. Confocal imaging of lung slices revealed that NEB cells responded to an increase of [Ca2+]o with a rise in intracellular Ca2+ ([Ca2+]i); an effect mimicked by several membrane-impermeant CaSR agonists (e.g. the calcimimetic R-568) and that was blocked by the calcilytic Calhex-231. Block of TRPC channels attenuated the CaSR-dependent increases in [Ca2+]i, suggesting that Ca2+ influx through TRPC channels contributes to the total [Ca2+]i signal evoked by the CaSR in NEBs. CaSR also regulated baseline [Ca2+]i in NEBs and, through paracrine signaling from Clara-like cells, coordinated intercellular communication in the NEB microenvironment. These data suggest that the NEB CaSR integrates multiple signals converging on this complex chemosensory unit, and is a key regulator of this intrapulmonary airway stem cell niche.
Photodynamic therapy with new sublingual sensitiser Photosoft®E4 for cancer: a case series
Authors: Ried Karin , Sali Avni , Wang Michelle , Meade Brian , Murphy Donald 
Published: July 2013

Background: An increasing number of patients seek complementary therapies for cancer treatment, the leading cause of death in the developed world. Photodynamic therapy (PDT), the combination of light and a photosensitiser agent, has provided some promising results in cancer therapy. New photosensitiser agents are continuously being developed to improve tolerability and effectiveness. There is a need to objectively evaluate clinical data from PDT patients.Methods: Here we report a case series using the new sublingually administered, chlorophyll-based photosensitiser Photosoft®E4 and an external laser light in a group of ten adult cancer patients not undergoing other concurrent therapies. PDT was administered for three treatment cycles with an average of 14 light treatments per patient, consisting of agent administration and laser treatment on alternate days over 3 months. Safety, tolerability and effectiveness on tumour palliation were monitored. Results: Patients in this study presented with a variety of cancer types and stages; half of the patients had breast cancer, and 40% had metastases. We found Photosoft®E4 to be safe and highly tolerable. However, overall disease status was not improved in our group of patients. Conclusions: Future research is required to determine the bioavailability of Photosoft®E4 and its uptake in tumour tissue, pharmacokinetics and dosing regimen, as well as the best mode of light delivery for the in vivo sensitiser activation.
Methods for Measuring Serum Activity Levels of the 192 Q and R Isoenzymes of Paraoxonase 1 in QR Heterozygous Individuals
Authors: Teiber John F , Kramer Gerald L , Haley Robert W 
Published: July 2013

BACKGROUND
Paraoxonase 1 (PON1), an esterase that hydrolyzes toxic organophosphates and has antioxidative and antiatherogenic properties, contains a common polymorphism at position 192: glutamine (Q) or arginine (R). The Q and R isoenzymes exhibit different physical and protective properties. We describe 2 methods for quantifying their serum activity levels.

METHODS
We measured serum hydrolytic activity with paraoxon [paraoxonase (PXN) activity], phenylacetate [arylesterase (AE) activity], and diazoxon [diazoxonase (DZN) activity] with standard automated assays. We determined PON1 Q192R genotypes with PCR and Q192R phenotypes using the PXN/AE and PXN/DZN ratios. Interpolation equations were empirically derived to predict the percentage of total PON1 hydrolytic activity due to the Q isoenzyme (%Q) from the PXN/AE and PXN/DZN ratios; %R is 100 − %Q. We estimated Q and R isoenzyme activity levels in sera from 2095 veterans by multiplying AE activity, a measure of total PON1 hydrolytic activity, by %Q and %R.

RESULTS
In all 2095 samples, the PXN/AE and PXN/DZN ratios predicted Q192R phenotypes with nearly identical accuracy (κ = 0.997). In the 925 QR heterozygotes, the 2 interpolation methods predicted Q and R isoenzyme activity levels with excellent agreement (intraclass correlation 0.94). After excluding a few genotype/phenotype-discordant samples, the percentage of total PON1 activity due to the Q isoenzyme ranged from 22% to 70%.

CONCLUSIONS
These new interpolation methods allow accurate estimation of PON1 192 Q and R isoenzyme activity levels, increasing specificity and power for studying susceptibility to disease.
Combined Time and Frequency Domain Approach to the Interpretation of Bender-Element Tests on Sand
Authors: Styler Mark A. , Howie John A. 
Published: July 2013

Abstract
Shear wave velocities are obtained from bender-element tests on laboratory specimens by analyzing the trigger and response signals. The response signal is a highly distorted translation of the trigger signal, obscuring the identification of the shear wave arrival. This has led to the publication of many criteria to guide subjective decisions on the selection of trigger waveform and frequency and of applicable interpretation methods. Current methods of interpretation result in determination of either the group or phase velocity. As soil and bender-element responses are dispersive, and as the group velocity is only valid in non-dispersive systems, the phase velocity should be measured. A combined time and frequency domain method is presented to allow interpretation of the phase velocity, minimizing subjective input to the interpretation. The method is first demonstrated using simplified synthetic signals and is then applied to laboratory test data. The reproducibility of the results is demonstrated from measurements on ten triaxial specimens of saturated Fraser River sand. The group velocities are shown to be very sensitive to dispersion, not reproducible, and contingent on the selected frequency window, whereas the phase velocities are considerably more repeatable. The combined time and frequency domain method results in the interpretation of a phase velocity using only measured parameters.
Defining Y2 Yielding From Cyclic Triaxial Tests
Authors: Zapata-Medina David G. , Finno Richard J. 
Published: July 2013

Abstract
This paper presents the yielding characteristics of overconsolidated Bootlegger Cove Formation (BCF) clays extracted from the Port of Anchorage construction site. Additionally, it extends the critical shear strain concept to define the point at which irrecoverable deformations begin (Y2 yielding) to the case of fully reversed loadings during undrained cyclic triaxial (CyTX) tests. On-specimen linear variable differential transformers (LVDTs) and an internal load cell with high accuracy were employed to define stress–strain responses and yield points of the specimens. This paper also presents Y2 yield points obtained using standard procedures available in the technical literature based on monotonic triaxial testing to show that the size and location of the Y2 yield surface can be determined from undrained CyTX tests.
Inflection Point Method to Estimate ch From Radial Consolidation Tests with Peripheral Drain
Authors: Ganesalingam Dhanya , Sivakugan Nagaratnam , Read Wayne 
Published: July 2013

Abstract
Horizontal coefficient of consolidation chis a key parameter in the design of vertical drains and the following consolidation analysis of a soil layer. There are graphical and non-graphical methods available to estimate ch from laboratory radial consolidation tests with a central drain. Currently, the consolidation tests with peripheral drains have to be analysed through a curve fitting method for determining ch. In this technical note, a non-graphical inflection point method is proposed for determining ch for an oedometer test with peripheral drainage, based on the characteristic feature observed when the gradient of the theoretical Ur –log Trrelationship was plotted against Tr. The proposed method is validated through a series of consolidation tests on two reconstituted dredged clay specimens, tested in an oedometer subjected to radial drainage with peripheral drains. The consolidation settlements predicted from the proposed method, for the two different clays, were in excellent agreement with those measured in the oedometer. The proposed method will be a very valuable tool in the analysis of radial consolidation data when the drains are peripheral.
Microstructural and Mineralogical Evaluation of the Effectiveness of Mixing Treatments in Stabilized Clays
Authors: Bellato Diego , Simonini Paolo , Dalle Coste Alberto 
Published: July 2013

Abstract
This paper shows and discusses the results of a comprehensive mineralogical and microstructural investigation carried out on several samples collected from diaphragm walls obtained treating a deposit of overconsolidated clay with the cutter soil mixing (CSM) technology, one of the most recent methods for deep mixing. To this purpose, scanning electron microscopy, X-ray powder diffraction analysis, mercury intrusion porosimetry, and X-ray computed micro-tomography were extensively used to measure soil properties at the micro-scale. In addition, unconfined compression tests and permeability tests were conducted to evaluate the effectiveness of CSM also at the macro-scale. The capability of CSM to treat cohesive soils seems to be confirmed by the experimental investigation carried out so far, considering, particularly, the degree of mixture homogeneity achieved at the end of the mixing procedure, together with the growth of several hydration products in the cemented matrix.
Load-Settlement Behavior of Drilled Shafts in Multilayered Deposits of Soils and Intermediate Geomaterials
Authors: Gupta Ramesh Chandra 
Published: July 2013

Abstract
Using a hyperbolic model and curve-fitting techniques, curves of the nonlinear side resistance (fs) versus the ratio of shaft displacement to shaft diameter (Δ/d), measured in top-down static load tests on instrumented drilled shafts in multilayered deposits of soil and intermediate geomaterials (IGMs), have been analyzed to determine the values of shear modulus (G) and ultimate side friction (fsu). Values of G and fsu for each layer of soil and IGM so determined from load tests matched well with those determined from correlations. An iterative procedure based on hyperbolic curves of fs versus Δ/d derived using values of G and fsu determined either from correlations or from load tests was used to compute or back-calculate top-down load-settlement curves. The load-settlement curves determined via this procedure matched well with those measured from the top-down load tests both when the tip bears above a cavity or very soft soils and when the tip is bearing in a firm and dense IGM. It was found that an accurate axial load distribution and settlement profile along the length of a shaft can be determined via this procedure.
Recent Changes in the Internet Landscape
Authors: Uhlig Steve , Cuadrado Latasa Felix 
Published: July 2013

Abstract
The Internet is in a state of constant flux. This property of the Internet, that stems from the pressure from its continuously reinvented usage, makes it a lively environment, which must be re-assessed fundamentally from time to time. In this article, we review recent trends that have radically changed our perception of what the Internet is. Popular applications such as Youtube and Facebook have demonstrated the massive scale at which services can be delivered across the Internet. This has been possible only thanks to the massive deployment in content delivery infrastructures, leading to the rise of the Cloud paradigm. Recent studies from the research community have observed the consequences of this growth in the Internet infrastructure, through structural changes in the Internet topology and traffic patterns. The increasingly dynamic nature of Internet traffic patterns asks for improved capabilities to engineer traffic, that require a completely different level of programmability from the network. Software-defined networking is expected to fill this gap. Overall, the picture of the Internet that we draw in this article is the one of a very dynamic, challenging, and exciting playground.
Crowdsourcing and its Impact on Future Internet Usage
Authors: Tran-Gia Phuoc , Hoßfeld Tobias , Hartmann Matthias , Hirth Matthias 
Published: July 2013

Abstract
Crowdsourcing is an emerging service platform and business model in the Internet. In contrast to outsourcing where a job is performed by a designated contractor, with Crowdsourcing, jobs are outsourced to a large, anonymous crowd of workers, the so-called human cloud. The rise of Crowdsourcing and its seamless integration in current workflows may have a huge impact on the Internet and on society, and will be a guiding paradigm that can form the evolution of work in the years to come. In this article, we discuss applications and use cases of Crowdsourcing to demonstrate the impact on Internet usage. Novel measurement approaches are presented and the impact of Crowdsourcing on Internet traffic is evaluated by measuring the activity of a particular Crowdsourcing platform. New technical solutions are necessary for the operation of efficient, distributed Crowdsourcing platforms. Special attention is drawn to the integration of machine clouds and human crowds, and appropriate inter-cloud solutions. Finally, we discuss current research challenges from a scientific and from the platform provider´s point of view.
A Federated CloudNet Architecture: The PIP and the VNP Role
Authors: Grassler Johannes , Schaffrath Gregor , Schmid Stefan 
Published: July 2013

Abstract
We present a generic and flexible architecture to realize CloudNets: virtual networks connecting geographically distributed cloud resources (such as storage or CPU) with resource guarantees. Our architecture is federated and supports different (and maybe even competing) economical roles, by providing explicit negotiation and provisioning interfaces. Contract-based interactions and a resource description language that allows for aggregation and abstraction, preserve the different roles´ autonomy without sacrificing flexibility. Moreover, since our CloudNet architecture is plugin based, essentially all cloud operating systems (e. g., OpenStack) or link technologies (e. g., VLANs, OpenFlow, VPLS) can be used within the framework. This paper describes two roles in more detail: The Physical Infrastructure Providers (PIP) which own the substrate network and resources, and the Virtual Network Providers (VNP) which can act as resource and CloudNet brokers and resellers. Both roles are fully implemented in our wide-area prototype that spans remote sites and resources.
Ontology-based Application Integration on the User Interface Level
Authors: Paulheim Heiko 
Published: July 2013

Abstract
Application integration can be performed on three levels: the data source level, the business logic level, and the user interface level. Approaches of the latter kind include, e. g., portal and mashup solutions. Deeper integration offering rich interaction possibilities usually leads to strong dependencies between applications, and requires deep knowledge of those applications. To reduce such dependencies, ontologies have been proposed as an inter-lingua mediating between the applications. While there have been approaches for using ontologies for integration on the data source and business logic level, this dissertation is the first approach for ontologybased application integration on the user interface level. It discusses the development of suitable formal ontologies, the use of reasoning and rule-based event processing, as well as aspects such as performance and seamless cross-technological interaction.