bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cowpox Virus Expresses a Novel Ankyrin Repeat NF-κB Inhibitor That Controls Inflammatory Cell Influx into Virus-Infected Tissues and Is Critical for Virus Pathogenesis
Authors: Mohamed Mohamed Ragaa , Rahman Masmudur M. , Rice Amanda , Moyer Richard W. , Werden Steven J. , McFadden Grant 
Published: July 2009

ABSTRACT
Many pathogenic orthopoxviruses like variola virus, monkeypox virus, and cowpox virus (CPXV), but not vaccinia virus, encode a unique family of ankyrin (ANK) repeat-containing proteins that interact directly with NF-κB1/p105 and inhibit the NF-κB signaling pathway. Here, we present the in vitro and in vivo characterization of the targeted gene knockout of this novel NF-κB inhibitor in CPXV. Our results demonstrate that the vCpx-006KO uniquely induces a variety of NF-κB-controlled proinflammatory cytokines from infected myeloid cells, accompanied by a rapid phosphorylation of the IκB kinase complex and subsequent degradation of the NF-κB cellular inhibitors IκBα and NF-κB1/p105. Moreover, the vCpx-006KO virus was attenuated for virulence in mice and induced a significantly elevated cellular inflammatory process at tissue sites of virus replication in the lung. These results indicate that members of this ANK repeat family are utilized specifically by pathogenic orthopoxviruses to repress the NF-κB signaling pathway at tissue sites of virus replication in situ.
The Spike Protein of Murine Coronavirus Regulates Viral Genome Transport from the Cell Surface to the Endoplasmic Reticulum during Infection
Authors: Zhu Hongqing , Yu Dongdong , Zhang Xuming 
Published: July 2009

ABSTRACT

We observed that the nonfusogenic mouse hepatitis virus (MHV) strain MHV-2 reached a titer of ∼2 log
10
higher than that of the fusogenic strain A59 in astrocytoma DBT cells. To determine whether the spike protein is responsible for the difference, a recombinant virus, Penn-98-1, that contains the A59 genome with a spike from MHV-2 was used to infect DBT cells. Results showed that Penn-98-1 behaved like MHV-2, thus establishing a role for the spike protein in viral growth. The inverse correlation between viral fusogenicity and growth was further established in four different cell types and with a fusogenic mutant, the S757R mutant, derived from isogenic Penn-98-1. While both A59 and Penn-98-1 entered cells at similar levels, viral RNA and protein syntheses were significantly delayed for A59. Interestingly, when the genomic RNAs were delivered directly into the cells via transfection, the levels of gene expression for these viruses were similar. Furthermore, cell fractionation experiments revealed that significantly more genomic RNAs for the nonfusogenic MHVs were detected in the endoplasmic reticulum (ER) within the first 2 h after infection than for the fusogenic MHVs. Pretreatment of Penn-98-1 with trypsin reversed its properties in syncytium formation, virus production, and genome transport to the ER. These findings identified a novel role for the spike protein in regulating the uncoating and delivery of the viral genome to the ER after internalization.
Role of Oxysterol Binding Protein in Hepatitis C Virus infection
Authors: Amako Yutaka , Sarkeshik Ali , Hotta Hak , Yates John , Siddiqui Aleem 
Published: July 2009

ABSTRACT
Hepatitis C virus (HCV) RNA genome replicates within the ribonucleoprotein (RNP) complex in the modified membranous structures extended from endoplasmic reticulum. A proteomic analysis of HCV RNP complexes revealed the association of oxysterol binding protein (OSBP) as one of the components of these complexes. OSBP interacted with the N-terminal domain I of the HCV NS5A protein and colocalized to the Golgi compartment with NS5A. An OSBP-specific short hairpin RNA that partially downregulated OSBP expression resulted in a decrease of the HCV particle release in culture supernatant with little effect on viral RNA replication. The pleckstrin homology (PH) domain located in the N-terminal region of OSBP targeted this protein to the Golgi apparatus. OSBP deletion mutation in the PH (ΔPH) domain failed to localize to the Golgi apparatus and inhibited the HCV particle release. These studies suggest a possible functional role of OSBP in the HCV maturation process.
Origin of Expression of the Herpes Simplex Virus Type 1 Protein U
S
1.5
Authors: Bowman J. Jason , Schaffer Priscilla A. 
Published: July 2009

ABSTRACT

ICP22, an immediate-early protein of herpes simplex virus type 1 (HSV-1), is required for viral replication in nonpermissive cell types and for expression of a class of late viral proteins which includes glycoprotein C. An understanding of the mechanism of ICP22 function has been complicated by the coexpression of the full-length protein with an in-frame, C-terminus-specific protein, U
S
1.5. In this report, we confirm that the U
S
1.5 protein is a bona fide translation product since it is detected during infections with three laboratory strains and two low-passage clinical isolates of HSV-1. To clarify the expression patterns of the ICP22 and U
S
1.5 proteins, we examined their synthesis from plasmids in transient expression assays. Because previous studies had identified two different U
S
1.5 translational start sites, we attempted to determine which is correct by studying the effects of a series of deletion, nonsense, and methionine substitutions on U
S
1.5 expression. First, amino acids 90 to 420 encoded by the ICP22 open reading frame (ORF) migrated at the mobility of U
S
1.5 in sodium dodecyl sulfate-polyacrylamide gels. Second, introduction of a stop codon downstream of M90 ablated expression of both ICP22 and U
S
1.5. Finally, mutation of M90 to alanine (M90A) allowed expression of full-length ICP22 while dramatically reducing expression of U
S
1.5. Levels of U
S
1.5 but not ICP22 protein expression were also reduced in cells infected with an M90A mutant virus. Thus, we conclude that expression of IC22 and that of U
S
1.5 can occur independently of each other and that U
S
1.5 translation initiates at M90 of the ICP22 ORF.
Inhibition of Macrophage Activation by the Myxoma Virus M141 Protein (vCD200)
Authors: Zhang Leiliang , Stanford Marianne , Liu Jia , Barrett Catherine , Jiang Lei , Barclay A. Neil , McFadden Grant 
Published: July 2009

ABSTRACT
The M141 protein of myxoma virus (MYXV) is a viral CD200 homolog (also called vOX-2) that inhibits macrophage activation in infected rabbits. Here, we show that murine myeloid RAW 264.7 cells became activated when infected with MYXV in which the M141 gene was deleted (vMyx-M141KO) but not with the parental wild-type MYXV. Moreover, transcript and protein levels of tumor necrosis factor and granulocyte colony-stimulating factor were rapidly upregulated in an NF-κB-dependent fashion in the RAW 264.7 cells infected with vMyx-M141KO. M141 protein is present in the virion and counteracts this NF-κB activation pathway upon infection with the wild-type MYXV. Our data suggest that upregulation of these classic macrophage-related proinflammatory cytokine markers following infection of myeloid cells with the M141-knockout MYXV is mediated via the rapid activation of the cellular NF-κB pathway.
Prion Infectivity in Fat of Deer with Chronic Wasting Disease
Authors: Race Brent , Meade-White Kimberly , Race Richard , Chesebro Bruce 
Published: July 2009

ABSTRACT
Chronic wasting disease (CWD) is a neurodegenerative prion disease of cervids. Some animal prion diseases, such as bovine spongiform encephalopathy, can infect humans; however, human susceptibility to CWD is unknown. In ruminants, prion infectivity is found in central nervous system and lymphoid tissues, with smaller amounts in intestine and muscle. In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.
Conventional Bone Marrow-Derived Dendritic Cells Contribute to Toll-Like Receptor-Independent Production of Alpha/Beta Interferon in Response to Inactivated Parapoxvirus Ovis
Authors: Siegemund Sabine , Hartl Andrea , von Buttlar Heiner , Dautel Franziska , Raue Rüdiger , Freudenberg Marina A. , Fejer György , Büttner Mathias , Köhler Gabriele , Kirschning Carsten J. , Sparwasser Tim , Alber Gottfried 
Published: July 2009

ABSTRACT

Parapoxvirus ovis (PPVO) is a member of the
Poxviridae
family and belongs to the genus
Parapoxvirus
. It displays only limited homology with orthopoxviruses and has some molecular features such as an unusual high GC content distinct from orthopoxviruses. Inactivated PPVO (iPPVO) displays strong immunostimulatory capacities mediating antiviral activity in vivo. The role of dendritic cells (DC) and the pattern recognition receptors and signaling requirements responsible for immunostimulation by iPPVO are unknown. We demonstrate here that bone marrow-derived plasmacytoid DC (BM-pDC) and bone marrow-derived conventional DC (BM-cDC) secrete alpha/beta interferon (IFN-α/β) in response to iPPVO. Furthermore, iPPVO induces tumor necrosis factor alpha (TNF-α) and interleukin-12/23p40 (IL-12/23p40) release and major histocompatibility complex class II (MHC-II), MHC-I, and CD86 upregulation by bone marrow-derived DC (BMDC). After engulfment, iPPVO is located in endosomal compartments and in the cytosol of BMDC. iPPVO elicits IFN-α/β by Toll-like receptor (TLR)-independent pathways in BM-cDC, since IFN-α/β release does not require myeloid differentiation primary response gene 88 (MyD88) or TIR-domain containing adaptor protein inducing interferon (TRIF). In contrast, iPPVO-induced TNF-α release and enhanced expression of MHC-I and CD86 but not of MHC-II by BMDC chiefly requires MyD88 but not TLR2 or TLR4. Induction of IFN-α by iPPVO in BM-cDC occurred in the absence of IFN regulatory factor 3 (IRF3) but required the presence of IRF7, whereas iPPVO-triggered IFN-β production required the presence of either IRF7 or IRF3. These results provide the first evidence that iPPVO mediates its immunostimulatory properties by TLR-independent and TLR-dependent pathways and demonstrate an important role of cDC for IFN-α/β production.
SEIZURE ABATEMENT WITH SINGLE DC PULSES: IS PHASE RESETTING AT PLAY?
Authors: OSORIO IVAN , FREI M. G. 
Published: July 2009

Topological approaches for seizure abatement have received scarce attention. The ability to reset the phase of biological oscillations has been widely exploited in cardiology, as evidenced in part by the usefulness of implantable of defibrillators, but not in epileptology. The aim of this work is to investigate the feasibility of seizure blockage using single or brief monophasic (DC) pulse trains. Single DC or brief (0.1 s) pulse trains were delivered manually or automatically to generalized seizures, induced in rats with the convulsant 3-mercaptoprionic acid, a GABA inhibitor. Treatment outcome (blocked vs. not blocked seizures) was ascertained visually and correlated with the "rhythmicity index", an indirect estimate of neuronal synchrony level. Blockage using single or brief (0.1 s) DC pulses was consistently achieved for seizures with a rhythmicity index > 0.6, while seizures with levels <0.6 were not, although transient phase changes in their oscillations were effected. This work reveals that level of neuronal synchronization may be an important factor in determining the probability of seizure blockage. Seizure blockage using single or brief DC pulse trains and its effects on neural tissue merit further investigation. The clinical applicability of this therapeutic modality and means to enhance it are discussed.
MAKESPAN MINIMIZATION WITH MACHINE AVAILABILITY CONSTRAINTS
Authors: FU BIN , HUO YUMEI , ZHAO HAIRONG 
Published: July 2009

We investigate the problems of scheduling n jobs to m machines with availability constraints. We consider two different models of availability constraints: the preventive model where the unavailability is due to preventive machine maintenance, and the fixed job model where the unavailability is due to a priori assignment of some of the n jobs to certain machines at certain times. In both models, the objective is to minimize the makespan. We assume that m is a constant, and if a job is interrupted by the unavailable interval, it can be resumed after the machine becomes available. For fixed job model, we show there is an FPTAS. For the preventive model, we show that if at least one machine is always available, then the PTAS for Multiple Subset Sum problem given by Kellerer can be applied to get a PTAS; otherwise, every machine has some unavailable intervals, we show that if (m - 1) machines each of which has unavailable intervals with total length bounded by α(n) · P sum /m where P sum is the total processing time of all jobs and α(n) can be any non-negative function, we can develop a (1 + α(n) + ∊)-approximation algorithm for any constant 0 < ∊ < 1; further we show that there does not exist any polynomial time (1 + α(n) - o(1))-approximation unless P = NP.
ON CONSTRUCTION OF ALMOST-RAMANUJAN GRAPHS
Authors: SUN HE , ZHU HONG 
Published: July 2009

O. Reingold et al. introduced the notion zig-zag product on two different graphs, and presented a fully explicit construction of d-regular expanders with the second largest eigenvalue O(d-1/3). In the same paper, they ask whether or not the similar technique can be used to construct expanders with the second largest eigenvalue O(d-1/2). Such graphs are called Ramanujan graphs. Recently, zig-zag product has been generalized by A. Ben-Aroya and A. Ta-Shma. Using this technique, they present a family of expanders with the second largest eigenvalue d-1/2 + o(1), what they call almost-Ramanujan graphs. However, their construction relies on local invertible functions and the dependence between the big graph and several small graphs, which makes the construction more complicated. In this paper, we shall give a generalized theorem of zig-zag product. Specifically, the zig-zag product of one "big" graph and several "small" graphs with the same size will be formalized. By choosing the big graph and several small graphs individually, we shall present a family of fully explicitly almost-Ramanujan graphs with locally invertible function waived.
Structure of the Madden–Julian Oscillation in the Superparameterized CAM
Authors: Benedict James J. , Randall David A. 
Published: July 2009

Abstract
The detailed dynamic and thermodynamic space–time structures of the Madden–Julian oscillation (MJO) as simulated by the superparameterized Community Atmosphere Model version 3.0 (SP-CAM) are analyzed. Superparameterization involves substituting conventional boundary layer, moist convection, and cloud parameterizations with a configuration of cloud-resolving models (CRMs) embedded in each general circulation model (GCM) grid cell. Unlike most GCMs that implement conventional parameterizations, the SP-CAM displays robust atmospheric variability on intraseasonal space and time (30–60 days) scales. The authors examine a 19-yr SP-CAM simulation based on the Atmospheric Model Intercomparison Project protocol, forced by prescribed sea surface temperatures. Overall, the space–time structures of MJO convective disturbances are very well represented in the SP-CAM. Compared to observations, the model produces a similar vertical progression of increased moisture, warmth, and heating from the boundary layer to the upper troposphere as deep convection matures. Additionally, important advective and convective processes in the SP-CAM compare favorably with those in observations. A deficiency of the SP-CAM is that simulated convective intensity organized on intraseasonal space–time scales is overestimated, particularly in the west Pacific. These simulated convective biases are likely due to several factors including unrealistic boundary layer interactions, a lack of weakening of the simulated disturbance over the Maritime Continent, and mean state differences.
The Final Warming Date of the Antarctic Polar Vortex and Influences on its Interannual Variability
Authors: Haigh Joanna D. , Roscoe Howard K. 
Published: July 2009

Abstract
More than 40 years of radiosonde data from two Antarctic stations are examined for changes in the date of the final stratospheric warming that occurs each year as the vortex breaks up in spring/summer. A new measure of this date is derived that does not rely on specification of a threshold, as has been common previously. The date of final warming takes between 10 and 40 days to progress from 30 to 100 hPa and occurs 20–30 days later in the 1990s than in the 1960s. Multiple linear regression analyses of these final warming dates, and also of the vertical profile of the southern annular mode (SAM), are presented. Only a weak signal is found for a linear trend, but a significant response is found throughout the atmosphere to ozone mass deficit (OMD), representing stratospheric ozone loss. In the SAM a significant response to the combined influence of solar variability and the quasi-biennial oscillation (QBO) is also found. The seasonal evolution of these signals in the NCEP Reanalysis zonal mean temperatures is examined and their influences on final warming dates is calculated. This confirms that ozone loss is primarily responsible for the delayed warming in the lower stratosphere in recent years, but suggests that the phase of solar activity and the QBO also have an effect. The apparent downward progression of the signal of OMD, and of the combined solar activity and QBO, extends well into the upper troposphere and appears to be caused simply by a delay in the top-down breakup of the vortex.
Observed Feedback between Winter Sea Ice and the North Atlantic Oscillation
Authors: Strong Courtenay , Magnusdottir Gudrun , Stern Hal 
Published: July 2009

Abstract
Feedback between the North Atlantic Oscillation (NAO) and winter sea ice variability is detected and quantified using approximately 30 years of observations, a vector autoregressive model (VAR), and testable definitions of Granger causality and feedback. Sea ice variability is quantified based on the leading empirical orthogonal function of sea ice concentration over the North Atlantic [the Greenland Sea ice dipole (GSD)], which, in its positive polarity, has anomalously high sea ice concentrations in the Labrador Sea region to the southwest of Greenland and low sea ice concentrations in the Barents Sea region to the northeast of Greenland. In weekly data for December through April, the VAR indicates that NAO index (N) anomalies cause like-signed anomalies of the standardized GSD index (G), and that G anomalies in turn cause oppositely signed anomalies of N. This negative feedback process operates explicitly on lags of up to four weeks in the VAR but can generate more persistent effects because of the autocorrelation of G. Synthetic data are generated with the VAR to quantify the effects of feedback following realistic local maxima of N and G, and also for sustained high values of G. Feedback can change the expected value of evolving system variables by as much as a half a standard deviation, and the relevance of these results to intraseasonal and interannual NAO and sea ice variability is discussed.
Evaluating Cloud Frequency of Occurrence and Cloud-Top Height Using Spaceborne Lidar Observations
Authors: Ahlgrimm Maike , Randall David A. , Köhler Martin 
Published: July 2009

Abstract
A strategy for model evaluation using spaceborne lidar observations is presented. Observations from the Geoscience Laser Altimeter System are recast onto the model grid to assess the ability of two versions of the Integrated Forecasting System to model marine stratocumulus clouds. The two model versions differ primarily in their treatment of clear and cloudy boundary layers. For each grid column, a representative cloud fraction and cloud-top height are derived from the observations, as well as from the model. By applying the same threshold criteria for cloud fraction and cloud-top height independently to model and observations, samples containing marine stratocumulus clouds can be identified. The frequency of occurrence, cloud fraction, and cloud-top height distributions for all samples thus identified are compared. The evaluation shows improvements in the frequency of occurrence and cloud-top height of marine stratocumulus, though modeled cloud tops remain lower than observed. Additional runs reveal a sensitivity to the strength of the environmental mixing that occurs during the test parcel ascent of the boundary layer parameterization. With a more aggressive parcel, the modeled clouds agree even better with observations.
In-Cloud Icing in the Columbia Basin
Authors: Thorkildson Ronald M. , Jones Kathleen F. , Emery Maggie K. 
Published: July 2009

Abstract
On 24 November 2005, 11 lattice steel towers of a high-voltage electrical transmission line running along the edge of an escarpment were damaged by an accumulation of rime on overhead ground wires. Cold air pooling in the Columbia basin of eastern Washington several days before the failure led to the formation of low-level fog and low clouds with temperatures below freezing at the elevation of the transmission line. The liquid water content profile of the cloud formed by air rising over Badger Mountain north of Wenatchee, Washington, is estimated using the air temperature, dewpoint temperature, and air pressure as measured at Wenatchee in the Columbia River valley below the line. Cloud median volume droplet diameters are estimated using typical droplet concentrations. The validity of the computed liquid water content is determined by comparing the measured cloud-base heights at Wenatchee with the calculated cloud-base heights. The mass and density of ice accreted on the ground wires and conductors of the transmission line are modeled using assumed wind speeds at the top of the escarpment with the estimated cloud properties. Results are compared with the density and mass of an ice sample retrieved from the field. This event is compared with other modeled in-cloud icing events from 1973 to 2007 using the period of record of Wenatchee weather data. This paper illustrates an approach for estimating the severity of in-cloud icing on the wires of transmission lines subject to cloud liquid water contents that have been enhanced by the local terrain.