bluuebunny/crossref_metadata_2025 huggingface dataset:
The C-Terminal α-Helix Domain of Apolipoprotein E Is Required for Interaction with Nonstructural Protein 5A and Assembly of Hepatitis C Virus
Authors: Cun Wei , Jiang Jieyun , Luo Guangxiang
Published: August 2010

We have recently demonstrated that human apolipoprotein E (apoE) is required for the infectivity and assembly of hepatitis C virus (HCV) (K. S. Chang, J. Jiang, Z. Cai, and G. Luo, J. Virol. 81:13783-13793, 2007; J. Jiang and G. Luo, J. Virol. 83:12680-12691, 2009). In the present study, we have determined the molecular basis underlying the importance of apoE in HCV assembly. Results derived from mammalian two-hybrid studies demonstrate a specific interaction between apoE and HCV nonstructural protein 5A (NS5A). The C-terminal third of apoE
per se
is sufficient for interaction with NS5A. Progressive deletion mutagenesis analysis identified that the C-terminal α-helix domain of apoE is important for NS5A binding. The N-terminal receptor-binding domain and the C-terminal 20 amino acids of apoE are dispensable for the apoE-NS5A interaction. The NS5A-binding domain of apoE was mapped to the middle of the C-terminal α-helix domain between amino acids 205 and 280. Likewise, deletion mutations disrupting the apoE-NS5A interaction resulted in blockade of HCV production. These findings demonstrate that the specific apoE-NS5A interaction is required for assembly of infectious HCV. Additionally, we have determined that using different major isoforms of apoE (E2, E3, and E4) made no significant difference in the apoE-NS5A interaction. Likewise, these three major isoforms of apoE are equally compatible with infectivity and assembly of infectious HCV, suggesting that apoE isoforms do not differentially modulate the infectivity and/or assembly of HCV in cell culture.
RNA Structures Required for Production of Subgenomic Flavivirus RNA
Authors: Funk Anneke , Truong Katherine , Nagasaki Tomoko , Torres Shessy , Floden Nadia , Balmori Melian Ezequiel , Edmonds Judy , Dong Hongping , Shi Pei-Yong , Khromykh Alexander A.
Published: August 2010

Flaviviruses are a group of single-stranded, positive-sense RNA viruses causing ∼100 million infections per year. We have recently shown that flaviviruses produce a unique, small, noncoding RNA (∼0.5 kb) derived from the 3′ untranslated region (UTR) of the genomic RNA (gRNA), which is required for flavivirus-induced cytopathicity and pathogenicity (G. P. Pijlman et al., Cell Host Microbe, 4: 579-591, 2008). This RNA (subgenomic flavivirus RNA [sfRNA]) is a product of incomplete degradation of gRNA presumably by the cellular 5′-3′ exoribonuclease XRN1, which stalls on the rigid secondary structure stem-loop II (SL-II) located at the beginning of the 3′ UTR. Mutations or deletions of various secondary structures in the 3′ UTR resulted in the loss of full-length sfRNA (sfRNA1) and production of smaller and less abundant sfRNAs (sfRNA2 and sfRNA3). Here, we investigated in detail the importance of West Nile virus Kunjin (WNV
KUN
) 3′ UTR secondary structures as well as tertiary interactions for sfRNA formation. We show that secondary structures SL-IV and dumbbell 1 (DB1) downstream of SL-II are able to prevent further degradation of gRNA when the SL-II structure is deleted, leading to production of sfRNA2 and sfRNA3, respectively. We also show that a number of pseudoknot (PK) interactions, in particular PK1 stabilizing SL-II and PK3 stabilizing DB1, are required for protection of gRNA from nuclease degradation and production of sfRNA. Our results show that PK interactions play a vital role in the production of nuclease-resistant sfRNA, which is essential for viral cytopathicity in cells and pathogenicity in mice.
Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus
Authors: Khatri Mahesh , Dwivedi Varun , Krakowka Steven , Manickam Cordelia , Ali Ahmed , Wang Leyi , Qin Zhuoming , Renukaradhya Gourapura J. , Lee Chang-Won
Published: August 2010

Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-γ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, γδ T cells, dendritic cells, activated T cells, and CD4+and CD8+T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.
Design of a Potentd-Peptide HIV-1 Entry Inhibitor with a Strong Barrier to Resistance
Authors: Welch Brett D. , Francis J. Nicholas , Redman Joseph S. , Paul Suparna , Weinstock Matthew T. , Reeves Jacqueline D. , Lie Yolanda S. , Whitby Frank G. , Eckert Debra M. , Hill Christopher P. , Root Michael J. , Kay Michael S.
Published: August 2010

The HIV gp41 N-trimer pocket region is an ideal viral target because it is extracellular, highly conserved, and essential for viral entry. Here, we report on the design of a pocket-specificd-peptide, PIE12-trimer, that is extraordinarily elusive to resistance and characterize its inhibitory and structural properties.d-Peptides (peptides composed ofd-amino acids) are promising therapeutic agents due to their insensitivity to protease degradation. PIE12-trimer was designed using structure-guided mirror-image phage display and linker optimization and is the firstd-peptide HIV entry inhibitor with the breadth and potency required for clinical use. PIE12-trimer has an ultrahigh affinity for the gp41 pocket, providing it with a reserve of binding energy (resistance capacitor) that yields a dramatically improved resistance profile compared to those of other fusion inhibitors. These results demonstrate that the gp41 pocket is an ideal drug target and establish PIE12-trimer as a leading anti-HIV antiviral candidate.
Fire-scar formation in Jeffrey pine – mixed conifer forests in the Sierra San Pedro Mártir, Mexico
Authors: Stephens Scott L. , Fry Danny L. , Collins Brandon M. , Skinner Carl N. , Franco-Vizcaíno Ernesto , Freed Travis J.
Published: August 2010

Little is known about the probability of fire-scar formation. In this study, we examined all mixed conifer trees for fire-scar formation in a 16 ha watershed that burned as part of a 2003 wildfire in Sierra San Pedro Mártir National Park (SSPM), Mexico. In addition, we examine the probability of fire-scar formation in relation to the previous fire interval in forests in the SSPM and Sierra Nevada. Within the 16 ha SSPM watershed, 1647 trees were assessed (100% census) for new fire scars. The SSPM wildfire burned around the base of 78% of the trees, but only 8% developed a new fire scar. Although the years from tree germination to first fire scar could potentially represent a fire-free period, there is clear evidence from this study that the inclusion of this interval when computing fire statistics is not justified. When the time since previous fire was <10 years, 10–30 years, and >57 years, the probability of rescarring was approximately 0.05, 0.5, and 0.75, respectively. In areas where fires were frequent (<10 years), fire frequencies derived from fire scars will likely underestimate true fire frequency, at least in forests that are similar to those studied here.
Role of tree stand evapotranspiration in maintaining satisfactory drainage conditions in drained peatlands
Authors: Sarkkola Sakari , Hökkä Hannu , Koivusalo Harri , Nieminen Mika , Ahti Erkki , Päivänen Juhani , Laine Jukka
Published: August 2010

Ditch networks in drained peatland forests are maintained regularly to prevent water table rise and subsequent decrease in tree growth. The growing tree stand itself affects the level of water table through evapotranspiration, the magnitude of which is closely related to the living stand volume. In this study, regression analysis was applied to quantify the relationship between the late summer water table depth (DWT) and tree stand volume, mean monthly summertime precipitation (Ps), drainage network condition, and latitude. The analysis was based on several large data sets from southern to northern Finland, including concurrent measurements of stand volume and summer water table depth. The identified model demonstrated a nonlinear effect of stand volume on DWT, a linear effect of Ps on DWT, and an interactive effect of both stand volume and Ps. Latitude and ditch depth showed only marginal influence on DWT. A separate analysis indicated that an increase of 10 m3·ha–1 in stand volume corresponded with a drop of 1 cm in water table level during the growing season. In a subsample of the data, high bulk density peat showed deeper DWT than peat with low bulk density at the same stand volume.
Five-year light, vegetation, and regeneration dynamics of boreal mixedwoods following silvicultural treatments to establish productive aspen–spruce mixtures in northeastern Ontario
Authors: Man Rongzhou , Rice James A. , MacDonald G. Blake
Published: August 2010

Given the extent of boreal mixedwoods in Canada and the challenges of maintaining their conifer component following harvest, we investigated the effects of intimate mixtures versus a mosaic spatial arrangement on mixedwood establishment and growth in northeastern Ontario. The silvicultural treatments were preharvest aerial herbicide spray, postharvest ground herbicide in conifer corridors, partial cutting, conventional conifer plantation with postharvest aerial herbicide, and an untreated reference stand. Fifth-year results suggest that preharvest herbicide application followed by clearcutting controlled trembling aspen ( Populus tremuloides Michx.) regeneration density and height growth nearly as effectively as postharvest herbicide in conifer corridors or the conventional conifer plantation treatments. Partial cutting reduced aspen regeneration in both harvested and leave corridors but did not affect shrub cover. Survival of spruce regeneration did not differ among silvicultural treatments; however, more spruce seedlings progressed from small to intermediate height classes in the preharvest spray and partial cut than in the postharvest herbicide treatment plots. Based on short-term responses in light availability, vegetation cover, and regeneration as well as cost comparisons among options, the treatment objectives were generally met: the stand has the desired species density and composition of a healthy and productive mixedwood.
Modeling mortality in mixed-species stands of coastal British Columbia
Authors: Rathbun Leah C. , LeMay Valerie , Smith Nick
Published: August 2010

Individual-tree distance-independent models were developed to estimate regular mortality for western hemlock ( Tsuga heterophylla (Raf.) Sarg.), Douglas-fir ( Pseudotsuga menziesii (Mirb.) Franco var. menziesii), and western redcedar ( Thuja plicata Donn ex D. Don) in the coastal temperate rain forests of British Columbia, Canada. Permanent plots remeasured at intervals ranging from 1 to 17 years were used. Because of the irregular remeasurement intervals, survival was estimated using a generalized logistic model and mortality was calculated by subtraction. Basal area of trees larger than the subject tree provided reasonably accurate mortality estimates for larger trees. However, poor results were obtained for trees less than 7.5 cm in diameter at breast height, which had higher mortality rates than the larger trees. Since the implementation of a survival (or mortality) model within a growth and yield model environment can largely affect estimation accuracy, three methods of implementing the model were also evaluated. A probability multiplier approach where the stems per hectare surviving to the next period is estimated by multiplying the probability of survival by the stems per hectare at the beginning of the time period is recommended. This is equivalent to a stochastic approach averaged over many repetitions but with much less processing time.
Characteristics of downed wood across headwater riparian ecotones: integrating the stream with the riparian area
Authors: Holmes Kathryn L. , Goebel P. Charles , Morris Arthur E.L.
Published: August 2010

Although downed wood is a significant structural component of riparian ecotones, most studies of downed wood dynamics are conducted only within the stream bankfull channel or on the riparian forest floor. We examined downed wood structural characteristics (e.g., length, volume, and decay class) across the entire riparian ecotone of seven headwater streams in mature deciduous forests of northeastern Ohio to understand the structural relationships between downed wood and riparian ecotones. Sampling was stratified by hydrogeomorphic zones that were defined by lateral position within the riparian ecotone and correspond to differing fluvial geomorphology. Most downed wood pieces sampled were small (<1 m) and with a high decay class. Downed wood pieces within the baseflow zone (within the wetted channel) were smaller and more abundant than those within the transitional zone (within the bankfull channel excluding the wetted channel). Surface contact was inversely related to aquatic influence across the riparian ecotone, with downed wood in Zone 3 (riparian area beyond the bankfull channel) having significantly higher contact than wood within the other zones. The ecotonal approach and the incorporation of hydrogeomorphic influences is an alternative approach that moves beyond traditional approaches to more holistic management of riparian forests.
Acoustic transmission of the chick-a-dee call of the Black-capped Chickadee (Poecile atricapillus): forest structure and note function
Authors: Proppe D. S. , Bloomfield L. L. , Sturdy C. B.
Published: August 2010

The acoustic adaptation hypothesis predicts that bird vocalizations will be structured to optimize their transmission through native vegetation. In cases where communication with distant individuals is needed, optimal transmission implies maximal propagation. In other cases, vocal signals are intended for nearby conspecifics and optimal transmission may be only a few metres. The “chick-a-dee” call of the Black-capped Chickadee ( Poecile atricapillus (L., 1766)) is a complex call used in both long- and short-range communication. Here we test whether this call transmits optimally in the locally preferred forests composed of a mix of deciduous and coniferous vegetation, or in either pure deciduous or coniferous forest stands. In addition, we examine whether notes that putatively function in short-range communication transmit shorter distances than those used in long-range communication. We found differential transmission rates for the highest and lowest frequencies in the chick-a-dee call in different forest types, and an overall improvement in call transmission in mixed forests. Note-type transmission correlated with putative note function with one notable exception. In summary, our results suggest that the chick-a-dee call conforms to the acoustic adaptation hypothesis, and that the forms of its note types are in line with their function.
Antioxidant responses to variations of oxygen by the Harderian gland of different species of the superspecies Spalax ehrenbergi
Authors: Soria-Valles C. , Caballero B. , Vega-Naredo I. , Sierra V. , Huidobro-Fernández C. , Gonzalo-Calvo D. D. , Tolivia D. , Rodríguez-Colunga M. J. , Joel A. , Coto-Montes A. , Avivi A.
Published: August 2010

The subterranean blind mole rats of the superspecies Spalax ehrenbergi (Nehring, 1898) have developed several strategies to cope with changing concentrations of underground oxygen. Such an atmosphere induces the generation of reactive oxygen species that can cause oxidative damage without proper control. To understand how S. ehrenbergi appear to be able to counteract the free radicals and avoid oxidative damage, we studied the oxidative status of the Harderian gland (an organ particularly vulnerable to oxidative stress in many rodents) in two species of the superspecies S. ehrenbergi ( Spalax galili and Spalax judaei ) under different oxygen concentration levels, paying special attention to the antioxidant defences developed by these animals and the resulting macromolecular damage. The results presented herein reinforce the idea that S. ehrenbergi deal better with hypoxic conditions than other rodents by regulating the activity of its antioxidant enzymes. Moreover, S. galili is better adapted to hypoxic conditions, whereas S. judaei appears to be better adapted to hyperoxic conditions.
Comment on “The structural relationship: regression in biology”
Authors: Dhanoa M. S. , Sanderson R.
Published: August 2010

Supplementary information relevant to structural relationship regression in biology as discussed by McArdle (1988; Can. J. Zool. 66(11): 2329–2339) is presented. Although McArdle presented both linear and multiple linear regression models, we limit our comment to the linear model only. McArdle’s eq. 2 is corrected. Deming’s alternative form of the maximum likelihood (ML) solution (Deming 1943; Statistical adjustment of data. John Wiley and Sons, Inc., New York) is introduced. In the ML solution, the ratio of the mean measurement variances of the y and x variables is assumed constant over the range of the data. However, when λMLis not constant, then iteratively reweighted generalized Deming regression or functional relationship estimation by maximum likelihood is more appropriate.
THE ROLE OF DOPAMINE IN THE MAINTENANCE OF WORKING MEMORY IN PREFRONTAL CORTEX NEURONS: INPUT-DRIVEN VERSUS INTERNALLY-DRIVEN NETWORKS
Authors: VERSACE MASSIMILIANO , ZORZI MARCO
Published: August 2010

How do organisms select and organize relevant sensory input in working memory (WM) in order to deal with constantly changing environmental cues? Once information has been stored in WM, how is it protected from and altered by the continuous stream of sensory input and internally generated planning? The present study proposes a novel role for dopamine (DA) in the maintenance of WM in the prefrontal cortex (Pfc) neurons that begins to address these issues. In particular, DA mediates the alternation of the Pfc network between input-driven and internally-driven states, which in turn drives WM updates and storage. A biologically inspired neural network model of Pfc is formulated to provide a link between the mechanisms of state switching and the biophysical properties of Pfc neurons. This model belongs to the recurrent competitive fields33class of dynamical systems which have been extensively mathematically characterized and exhibit the two functional states of interest: input-driven and internally-driven. This hypothesis was tested with two working memory tasks of increasing difficulty: a simple working memory task and a delayed alternation task. The results suggest that optimal WM storage in spite of noise is achieved with a phasic DA input followed by a lower DA sustained activity. Hypo and hyper-dopaminergic activity that alter this ideal pattern lead to increased distractibility from non-relevant pattern and prolonged perseverations on presented patterns, respectively.
SINGLE-TRIAL BASED INDEPENDENT COMPONENT ANALYSIS ON MISMATCH NEGATIVITY IN CHILDREN
Authors: CONG FENGYU , KALYAKIN IGOR , HUTTUNEN-SCOTT TIINA , LI HONG , LYYTINEN HEIKKI , RISTANIEMI TAPANI
Published: August 2010

Independent component analysis (ICA) does not follow the superposition rule. This motivates us to study a negative event-related potential — mismatch negativity (MMN) estimated by the single-trial based ICA (sICA) and averaged trace based ICA (aICA), respectively. To sICA, an optimal digital filter (ODF) was used to remove low-frequency noise. As a result, this study demonstrates that the performance of the sICA+ODF and aICA could be different. Moreover, MMN under sICA+ODF fits better with the theoretical expectation, i.e., larger deviant elicits larger MMN peak amplitude.
MUSCLE EMULATION WITH DC MOTOR AND NEURAL NETWORKS FOR BIPED ROBOTS
Authors: SERHAN HAYSSAM , NASR CHAIBAN G. , HENAFF PATRICK
Published: August 2010

This paper shows how to use a DC motor and its PID controller, to behave analogously to a muscle. A model of the muscle that has been learned by a NNARX (Neural Network Auto Regressive eXogenous) structure is used. The PID parameters are tuned by an MLP Network with a special indirect online learning algorithm. The calculation of the learning algorithm is performed based on a mathematical equation of the DC motor or with a Neural Network identification of the motor. For each of the two algorithms, the output of the muscle model is used as a reference for the DC motor control loop. The results show that we succeeded in forcing the physical system to behave in the same way as the muscle model with acceptable margin of error. An implementation in the knees of a simulated biped robot is realized. Simulation compares articular trajectories with and without the muscle emulator and shows that with muscle emulator, articular trajectories become closer to the human being ones and that total power consumption is reduced.
SCATTERING OF SCALAR PERTURBATIONS WITH COSMOLOGICAL CONSTANT IN LOW-ENERGY AND HIGH-ENERGY REGIMES
Authors: LIU MOLIN , YU BENHAI , WANG RUMIN , XU LIXIN
Published: August 2010

We study the absorption and scattering of massless scalar waves propagating in spherically symmetric spacetimes with dynamical cosmological constant both in low-energy and high-energy zones. In the former low-energy regime, we solve analytically the Regge–Wheeler wave equation and obtain an analytic absorption probability expression which varies with [Formula: see text], where M is the central mass and Λ is cosmological constant. The low-energy absorption probability, which is in the range of [0, 0.986701], increases monotonically with increase in Λ. In the latter high-energy regime, the scalar particles adopt their geometric optics limit value. The trajectory equation with effective potential emerges and the analytic high-energy greybody factor, which is relevant with the area of classically accessible regime, also increases monotonically with increase in Λ, as long Λ is less than or of the order of 104. In this high-energy case, the null cosmological constant result reduces to the Schwarzschild value [Formula: see text].
BENDING OF LIGHT IN ELLIS WORMHOLE GEOMETRY
Authors: BHATTACHARYA AMRITA , POTAPOV ALEXANDER A.
Published: August 2010

A recent work by Dey and Sen derived the approximate light deflection angle α by an Ellis wormhole in terms of proper radial distance ℓ that covers the entire spacetime. On the other hand, Bodenner and Will calculated the expressions for light bending in Schwarzschild geometry using various coordinates and showed that they all reduce to a single formula when re-expressed in the coordinate independent language of "circumferential radius" rC identified with the standard radial coordinate rS. We shall argue that the coordinate invariant language for two-way wormholes should be ℓ rather than rS. Hence here we find the exact deflection α in Ellis wormhole geometry first in terms of ℓ and then in terms of rS. We confirm the latter expression using three different methods. We argue that the practical measurement scheme does not necessarily single out either ℓ or rS. Some errors in the literature are corrected.
DIFFERENTIAL THERMOGRAPHY FOR EXPERIMENTAL, FULL-FIELD STRESS ANALYSIS OF HIP ARTHROPLASTY
Authors: ZANETTI ELISABETTA M. , AUDENINO ALBERTO L.
Published: August 2010

A hip prosthesis implant produces a significant deviation in the stress pattern compared with the physiologic condition. In this work, the stress patterns are evaluated experimentally on synthetic femora, by means of thermoelastic stress analysis. Two factors have been considered: stem implantation and head offset. Stress maps were obtained using differential thermography and correlated to these factors.

Thermoelastic stress maps have demonstrated to be sensitive to the implant and the head offset. In detail, the standard deviation of stresses can reduce from –5% to –50% (with reference to the physiologic one), depending on stem design; peak stresses change their position or disappear for different implant position or press-fitting, the sensitivity of average stresses to the offset is at least equal to 0.07 MPa/mm.

On the whole, a methodology was developed, allowing the experimental evaluation and comparison of the stress distributions produced by different implants.
CARDIAC ARRHYTHMIA DIAGNOSIS USING A NEURO-FUZZY APPROACH
Authors: BENALI R. , DIB N. , REGUIG BEREKSI F.
Published: August 2010

The ventricular premature contractions (VPC) are cardiac arrhythmias that are widely encountered in the cardiologic field. They can be detected using the electrocardiogram (ECG) signal parameters. A novel method for detecting VPC from the ECG signal is proposed using a new algorithm (Slope) combined with a fuzzy-neural network (FNN).

To achieve this objective, an algorithm for QRS detection is first implemented, and then a neuro-fuzzy classifier is developed. Its performances are evaluated by computing the percentages of sensitivity (SE), specificity (SP), and correct classification (CC). This classifier allows extraction of rules (knowledge base) to clarify the obtained results. We use the medical database (MIT-BIH) to validate our results.
Networked systems research at Akamai
Authors: Nygren Erik , Sitaraman Ramesh K. , Wein Joel
Published: August 2010

In this special section of OSR, we present a selection of research papers that relate to Akamai's platform and technology.
The Akamai network
Authors: Nygren Erik , Sitaraman Ramesh K. , Sun Jennifer
Published: August 2010

Comprising more than 61,000 servers located across nearly 1,000 networks in 70 countries worldwide, the Akamai platform delivers hundreds of billions of Internet interactions daily, helping thousands of enterprises boost the performance and reliability of their Internet applications. In this paper, we give an overview of the components and capabilities of this large-scale distributed computing platform, and offer some insight into its architecture, design principles, operation, and management.
Scaling a monitoring infrastructure for the Akamai network
Authors: Repantis Thomas , Cohen Jeff , Smith Scott , Wein Joel
Published: August 2010

We describe the design of, and experience with, Query, a monitoring system that supports the Akamai EdgePlatform. Query is a foundation of Akamai's approach to administering its distributed computing platform, allowing administrators, operations staff, developers, customers, and automated systems near real-time access to data about activity in Akamai's network. Users extract information regarding the current state of the network via a SQL-like interface. Versions of Query have been deployed since the inception of Akamai's platform, and it has scaled to support a distributed platform of 60,000+ servers, collecting over 200 gigabytes of data and answering over 30,000 queries approximately every 2 minutes.
Akamai state of the internet report, Q4 2009
Authors: Belson David
Published: August 2010

In this paper, we review data gathered across Akamai's global server network about attack traffic, Internet and broadband penetration, and mobile connectivity, as well as trends seen in this data over time.
QoS-oriented control of server systems
Authors: Malrait Luc
Published: August 2010

Multi-tier architectures are widely used by internet applications. Guaranteeing the performance, and more generally the quality of service (QoS), of such applications remains a crucial issue. In this paper we propose a methodology to get the optimal admission control of multi-tier server systems under high loads for one QoS objective. First we present a model of multi-tier server systems using fluid approximations. Second, we state and solve an optimization problem which consists in finding the configuration that maximizes the availability of the system for a given performance constraint. Simulations of both model and control from this preliminary work are presented. They show that the optimal configuration of such systems is not always intuitive.
The ECIR 2010 large scale hierarchical classification workshop
Authors: Kosmopoulos A. , Gaussier E. , Paliouras G. , Aseervatham S.
Published: August 2010

This paper reports on the Large Scale Hierarchical Classification workshop (http://kmi.open.ac.uk/events/ecir2010/workshops-tutorials), held in conjunction with the European Conference on Information Retrieval (ECIR) 2010. The workshop was associated with the PASCAL 2 Large-Scale Hierarchical Text Classification Challenge (http://lshtc.iit.demokritos.gr), which took place in 2009. We first provide information about the challenge, presenting the data used, the tasks and the evaluation measures and then we provide an overview of the approaches proposed by the participants of the workshop, together with a summary of the results of the challenge.
Information access for personal media archives
Authors: Doherty Aiden R. , Gurrin Cathal , Jones Gareth J.F. , Smeaton Alan F.
Published: August 2010

It is now possible to archive much of our life experiences in digital form using a variety of sources, e.g. blogs written, tweets made, photographs taken, etc. Information can be captured from a myriad of personal information devices. In this workshop, researchers from diverse disciplines discussed how we can advance towards the goal of effective capture, retrieval and exploration of e-memories. Proposed solutions included advanced textile sensors to capture new data, P2P methods to store this data, and personal reflection applications to review this data. Much discussion centered around search and navigation strategies, interactive interfaces, and the cognitive basis in using digitally captured information as memorabilia.
Report on INEX 2009
Authors: Beckers T. , Bellot P. , Demartini G. , Denoyer L. , De Vries C. M. , Doucet A. , Fachry K. N. , Fuhr N. , Gallinari P. , Geva S. , Huang W.-C. , Iofciu T. , Kamps J. , Kazai G. , Koolen M. , Kutty S. , Landoni M. , Lehtonen M. , Moriceau V. , Nayak R. , Nordlie R. , Pharo N. , SanJuan E. , Schenkel R. , Tannier X. , Theobald M. , Thom J. A. , Trotman A. , de Vries A. P.
Published: August 2010

INEX investigates focused retrieval from structured documents by providing large test collections of structured documents, uniform evaluation measures, and a forum for organizations to compare their results. This paper reports on the INEX 2009 evaluation campaign, which consisted of a wide range of tracks: Ad hoc, Book, Efficiency, Entity Ranking, Interactive, QA, Link the Wiki, and XML Mining. INEX in running entirely on volunteer effort by the IR research community: anyone with an idea and some time to spend, can have a major impact.
Multimedia with a speech track
Authors: Larson Martha , Ordelman Roeland , de Jong Franciska , Kohler Joachim , Kraaij Wessel
Published: August 2010

After two successful years at SIGIR in 2007 and 2008, the third workshop on
Searching Spontaneous Conversational Speech (SSCS 2009)
was held conjunction with the ACM Multimedia 2009. The goal of the SSCS series is to serve as a forum that brings together the disciplines that collaborate on spoken content retrieval, including information retrieval, speech recognition and multimedia analysis. Multimedia collections often contain a speech track, but in many cases it is ignored or not fully exploited for information retrieval. Currently, spoken content retrieval research is expanding beyond highly-conventionalized domains such as broadcast news in to domains involving speech that is produced spontaneously and in conversational settings. Such speech is characterized by wide variability of speaking styles, subject matter and recording conditions. The work presented at SSCS 2009 included techniques for searching meetings, interviews, telephone conversations, podcasts and spoken annotations. The work encompassed a large range of approaches including using subword units, exploiting dialogue structure, fusing retrieval models, modeling topics and integrating visual features. Taken in sum, the workshop demonstrated the high potential of new ideas emerging in the area of speech search and also reinforced the need for concentrated research devoted to the classic challenges of spoken content retrieval, many of which remain yet unsolved.
Senescence and dysfunction of proximal tubular cells are associated with activated p53 expression by indoxyl sulfate
Authors: Shimizu Hidehisa , Bolati Dilinaer , Adijiang Ayinuer , Enomoto Atsushi , Nishijima Fuyuhiko , Dateki Minori , Niwa Toshimitsu
Published: August 2010

Various uremic toxins accumulate in patients with chronic renal failure (CRF) and one of them is indoxyl sulfate, which accelerates the progression of CRF through unknown mechanisms. The present study investigates how indoxyl sulfate promotes CRF using the proximal tubular cell line HK-2 and CRF rats. Indoxyl sulfate inhibited serum-induced cell proliferation and promoted the activation of senescence-associated β-galactosidase, a marker of cellular senescence, and the expression of α-smooth muscle actin (α-SMA), a marker of fibrosis, through inducing p53 expression and phosphorylation. Pifithrin-α, p-nitro, a p53 inhibitor, blocked these effects. Indoxyl sulfate evoked reactive oxygen species (ROS), and the antioxidant N-acetylcysteine inhibited indoxyl sulfate-induced p53 expression and phosphorylation, as well as indoxyl sulfate-induced α-SMA expression. We previously demonstrated that although cellular senescence and fibrosis are detectable in the kidneys of CRF rats, the oral adsorbent AST-120 repressed these effects. Here, we found that β-galactosidase, p53 and α-SMA were expressed and colocalized in the renal tubules of CRF rats, whereas AST-120 decreased the expression of these genes. Taken together, these findings indicate that indoxyl sulfate induces the expression and phosphorylation of p53 though ROS production, thus inhibiting cell proliferation and promoting cellular senescence and renal fibrosis.
Muscle protein synthesis and gene expression during recovery from aerobic exercise in the fasted and fed states
Authors: Harber Matthew P. , Konopka Adam R. , Jemiolo Bozena , Trappe Scott W. , Trappe Todd A. , Reidy Paul T.
Published: August 2010

The purpose of this investigation was to assess mixed-muscle fractional synthesis rate (FSR) and the expression of genes involved in skeletal muscle remodeling after aerobic exercise in the fasted and fed states. Eight recreationally active males (25 ± 1 yr; V̇o2 max: 52 ± 2 ml·kg−1·min−1) performed 60-min of cycle ergometry at 72 ± 1% V̇o2 maxon two occasions in a counter-balanced design. Subjects ingested a noncaloric placebo (EX-FAST) or a beverage containing (per kg body wt): 5 kcal, 0.83 g carbohydrate, 0.37 g protein, and 0.03 g fat (EX-FED) immediately and 1 h after exercise. FSR was assessed at rest and following exercise with the use of a l-[ring2H5]-phenylalanine infusion combined with muscle biopsies at 2 and 6 h postexercise. mRNA expression was assessed at 2 and 6 h postexercise via real-time RT-PCR. FSR was higher ( P < 0.05) after exercise in both EX-FAST (0.112 ± 0.010%·h−1) and EX-FED (0.129 ± 0.014%·h−1) compared with rest (0.071 ± 0.005%·h−1). Feeding attenuated the mRNA expression ( P < 0.05) of proteolytic factors MuRF-1 (6 h) and calpain-2 (2 and 6 h) postexercise but did not alter FOXO3A, calpain-1, caspase3, or myostatin mRNA expression compared with EX-FAST. Myogenic regulatory factor (MRF4) mRNA was also attenuated ( P < 0.05) at 2 and 6 h postexercise in EX-FED compared with EX-FAST. These data demonstrate that a nonexhaustive bout of aerobic exercise stimulates skeletal muscle FSR in the fasted state and that feeding does not measurably enhance FSR between 2 and 6 h after aerobic exercise. Additionally, postexercise nutrient intake attenuates the expression of factors involved in the ubiquitin-proteosome and Ca2+-dependent protein degradation pathways. These data provide insight into the role of feeding on muscle protein metabolism during recovery from aerobic exercise.
Shear stress increases nitric oxide production in thick ascending limbs
Authors: Cabral Pablo D. , Hong Nancy J. , Garvin Jeffrey L.
Published: August 2010

We showed that luminal flow stimulates nitric oxide (NO) production in thick ascending limbs. Ion delivery, stretch, pressure, and shear stress all increase when flow is enhanced. We hypothesized that shear stress stimulates NO in thick ascending limbs, whereas stretch, pressure, and ion delivery do not. We measured NO in isolated, perfused rat thick ascending limbs using the NO-sensitive dye DAF FM-DA. NO production rose from 21 ± 7 to 58 ± 12 AU/min ( P < 0.02; n = 7) when we increased luminal flow from 0 to 20 nl/min, but dropped to 16 ± 8 AU/min ( P < 0.02; n = 7) 10 min after flow was stopped. Flow did not increase NO in tubules from mice lacking NO synthase 3 (NOS 3). Flow stimulated NO production by the same extent in tubules perfused with ion-free solution and physiological saline (20 ± 7 vs. 24 ± 6 AU/min; n = 7). Increasing stretch while reducing shear stress and pressure lowered NO generation from 42 ± 9 to 17 ± 6 AU/min ( P < 0.03; n = 6). In the absence of shear stress, increasing pressure and stretch had no effect on NO production (2 ± 8 vs. 8 ± 8 AU/min; n = 6). Similar results were obtained in the presence of tempol (100 μmol/l), a O2−scavenger. Primary cultures of thick ascending limb cells subjected to shear stresses of 0.02 and 0.55 dyne/cm2produced NO at rates of 55 ± 10 and 315 ± 93 AU/s, respectively ( P < 0.002; n = 7). Pretreatment with the NOS inhibitor l-NAME (5 mmol/l) blocked the shear stress-induced increase in NO production. We concluded that shear stress rather than pressure, stretch, or ion delivery mediates flow-induced stimulation of NO by NOS 3 in thick ascending limbs.
Role of the Rhesus glycoprotein, Rh B glycoprotein, in renal ammonia excretion
Authors: Bishop Jesse M. , Verlander Jill W. , Lee Hyun-Wook , Nelson Raoul D. , Weiner Arthur J. , Handlogten Mary E. , Weiner I. David
Published: August 2010

Rh B glycoprotein (Rhbg) is a member of the Rh glycoprotein family of ammonia transporters. In the current study, we examine Rhbg's role in basal and acidosis-stimulated acid-base homeostasis. Metabolic acidosis induced by HCl administration increased Rhbg expression in both the cortex and outer medulla. To test the functional significance of increased Rhbg expression, we used a Cre-loxP approach to generate mice with intercalated cell-specific Rhbg knockout (IC-Rhbg-KO). On normal diet, intercalated cell-specific Rhbg deletion did not alter urine ammonia excretion, pH, or titratable acid excretion significantly, but it did decrease glutamine synthetase expression in the outer medulla significantly. After metabolic acidosis was induced, urinary ammonia excretion was significantly less in IC-Rhbg-KO than in control (C) mice on days 2–4 of acid loading, but not on day 5. Urine pH and titratable acid excretion and dietary acid intake did not differ significantly between acid-loaded IC-Rhcg-KO and C mice. In IC-Rhbg-KO mice, acid loading increased connecting segment (CNT) cell and outer medullary collecting duct principal cell Rhbg expression. In both C and IC-Rhbg-KO mice, acid loading decreased glutamine synthetase in both the cortex and outer medulla; the decrease on day 3 was similar in IC-Rhbg-KO and C mice, but on day 5 it was significantly greater in IC-Rhbg-KO than in C mice. We conclude 1) intercalated cell Rhbg contributes to acidosis-stimulated renal ammonia excretion, 2) Rhbg in CNT and principal cells may contribute to renal ammonia excretion, and 3) decreased glutamine synthetase expression may enable normal rates of ammonia excretion under both basal conditions and on day 5 of acid loading in IC-Rhbg-KO mice.
A single residue in transmembrane domain 11 defines the different affinity for thiazides between the mammalian and flounder NaCl transporters
Authors: Castañeda-Bueno María , Vázquez Norma , Bustos-Jaimes Ismael , Hernández Damian , Rodríguez-Lobato Erika , Pacheco-Alvarez Diana , Cariño-Cortés Raquel , Moreno Erika , Bobadilla Norma A. , Gamba Gerardo
Published: August 2010

Little is known about the residues that control the binding and affinity of thiazide-type diuretics for their protein target, the renal Na+-Cl−cotransporter (NCC). Previous studies from our group have shown that affinity for thiazides is higher in rat (rNCC) than in flounder (flNCC) and that the transmembrane region (TM) 8–12 contains the residues that produce this difference. Here, an alignment analysis of TM 8–12 revealed that there are only six nonconservative variations between flNCC and mammalian NCC. Two are located in TM9, three in TM11, and one in TM12. We used site-directed mutagenesis to generate rNCC containing flNCC residues, and thiazide affinity was assessed using Xenopus laevis oocytes. Wild-type or mutant NCC activity was measured using22Na+uptake in the presence of increasing concentrations of metolazone. Mutations in TM11 conferred rNCC an flNCC-like affinity, which was caused mostly by the substitution of a single residue, S575C. Supporting this observation, the substitution C576S conferred to flNCC an rNCC-like affinity. Interestingly, the S575C mutation also rendered rNCC more active. Substitution of S575 in rNCC for other residues, such as alanine, aspartate, and lysine, did not alter metolazone affinity, suggesting that reduced affinity in flNCC is due specifically to the presence of a cysteine. We conclude that the difference in metolazone affinity between rat and flounder NCC is caused mainly by a single residue and that this position in the protein is important for determining its functional properties.
Polycystic kidney disease in Han:SPRD Cy rats is associated with elevated expression and mislocalization of SamCystin
Authors: Nagao Shizuko , Morita Miwa , Kugita Masanori , Yoshihara Daisuke , Yamaguchi Tamio , Kurahashi Hiroki , Calvet James P. , Wallace Darren P.
Published: August 2010

Polycystic kidney disease (PKD) in Han:SPRD Cy rats is caused by a missense mutation in Anks6 (also called Pkdr1), leading to an R823W substitution in SamCystin, a protein that contains ankyrin repeats and a sterile alpha motif (SAM). The cellular function of SamCystin and the role of the Cy (R823W) mutation in cyst formation are unknown. In normal SPRD rats, SamCystin was found to be expressed in proximal tubules and glomeruli; protein expression was highest at 7 days of age and declined by ∼50–60% at 45–84 days of age. In Cy/+ and Cy/Cy kidneys, expression of SamCystin was lower than in +/+ kidneys at 3 and 7 days but became elevated at 21 days. Immunohistochemical analysis revealed that SamCystin was distributed on the brush border of proximal tubules in normal rat kidneys. In Cy/+ kidneys, there were robust SamCystin staining in cyst-lining epithelial cells and loss of apical localization, and increased number of PCNA-positive cells in cyst-lining epithelia. Verapamil, an L-type Ca2+channel blocker, accelerated PKD progression in this model and caused a further increase in the expression and abnormal distribution of SamCystin. We conclude that aberrant expression and mislocalization of R823W SamCystin lead to increased cell proliferation and renal cyst formation.
Acute l-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance
Authors: Bailey Stephen J. , Winyard Paul G. , Vanhatalo Anni , Blackwell Jamie R. , DiMenna Fred J. , Wilkerson Daryl P. , Jones Andrew M.
Published: August 2010

It has recently been reported that dietary nitrate (NO3−) supplementation, which increases plasma nitrite (NO2−) concentration, a biomarker of nitric oxide (NO) availability, improves exercise efficiency and exercise tolerance in healthy humans. We hypothesized that dietary supplementation with l-arginine, the substrate for NO synthase (NOS), would elicit similar responses. In a double-blind, crossover study, nine healthy men (aged 19–38 yr) consumed 500 ml of a beverage containing 6 g of l-arginine (Arg) or a placebo beverage (PL) and completed a series of “step” moderate- and severe-intensity exercise bouts 1 h after ingestion of the beverage. Plasma NO2− concentration was significantly greater in the Arg than the PL group (331 ± 198 vs. 159 ± 102 nM, P < 0.05) and systolic blood pressure was significantly reduced (123 ± 3 vs. 131 ± 5 mmHg, P < 0.01). The steady-state O2 uptake (V̇o2) during moderate-intensity exercise was reduced by 7% in the Arg group (1.48 ± 0.12 vs. 1.59 ± 0.14 l/min, P < 0.05). During severe-intensity exercise, the V̇o2 slow component amplitude was reduced (0.58 ± 0.23 and 0.76 ± 0.29 l/min in Arg and PL, respectively, P < 0.05) and the time to exhaustion was extended (707 ± 232 and 562 ± 145 s in Arg and PL, respectively, P < 0.05) following consumption of Arg. In conclusion, similar to the effects of increased dietary NO3− intake, elevating NO bioavailability through dietary l-Arg supplementation reduced the O2 cost of moderate-intensity exercise and blunted the V̇o2 slow component and extended the time to exhaustion during severe-intensity exercise.
Neural Substrate of an Increase in Sensory Sampling Triggered by a Motor Command in a Gymnotid Fish
Authors: Comas Virginia , Borde Michel
Published: August 2010

Despite recent advances that have elucidated the effects of collateral of motor commands on sensory processing structures, the neural mechanisms underlying the modulation of active sensory systems by internal motor-derived signals remains poorly understood. This study deals with the neural basis of the modulation of the motor component of an active sensory system triggered by a central motor command in a gymnotid fish. In Gymnotus omarorum, activation of Mauthner cells, a pair of reticulospinal neurons responsible for the initiation of escape responses in most teleosts, evokes an abrupt and prolonged increase in the rate of the electric organ discharge (EOD), the output signal of the electrogenic component of the active electrosensory system. We show here that prepacemaker neural structures (PPs) that control the discharge of the command nucleus for EODs are key elements of this modulation. Retrograde labeling combined with injections of glutamate at structures that contain labeled neurons showed that PPs are composed of a bilateral group of dispersed brain stem neurons that extend from the diencephalon to the caudal medulla. Blockade of discrete PPs regions during the Mauthner cell–initiated electrosensory modulation indicate that the long duration of this modulation relied on activation of diencephalic PPs, whereas its peak amplitude depended on the recruitment of medullary PPs. Temporal correlation of motor and sensory consequences of Mauthner cell activation suggests that the Mauthner cell–initiated enhancement of electrosensory sampling is involved in the selection of escape trajectory.