bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin Profiling of Epstein-Barr Virus Latency Control Region
Authors: Day Latasha , Chau Charles M. , Nebozhyn Michael , Rennekamp Andrew J. , Showe Michael , Lieberman Paul M. 
Published: April 2007

ABSTRACTEpstein-Barr virus (EBV) escapes host immunity by the reversible and epigenetic silencing of immunogenic viral genes. We previously presented evidence that a dynamic chromatin domain, which we have referred to as the latency control region (LCR), contributes to the reversible repression of EBNA2 and LMP1 gene transcription. We now explore the protein-DNA interaction profiles for a few known regulatory factors and histone modifications that regulate LCR structure and activity. A chromatin immunoprecipitation assay combined with real-time PCR analysis was used to analyze protein-DNA interactions at ∼500-bp intervals across the first 60,000 bp of the EBV genome. We compared the binding patterns of EBNA1 with those of the origin recognition complex protein ORC2, the chromatin boundary factor CTCF, the linker histone H1, and several histone modifications. We analyzed three EBV-positive cell lines (MutuI, Raji, and LCL3459) with distinct transcription patterns reflecting different latency types. Our findings suggest that histone modification patterns within the LCR are complex but reflect differences in each latency type. The most striking finding was the identification of CTCF sites immediately upstream of the Qp, Cp, and EBER transcription initiation regions in all three cell types. In transient assays, CTCF facilitated EBNA1-dependent transcription activation of Cp, suggesting that CTCF coordinates interactions between different chromatin domains. We also found that histone H3 methyl K4 clustered with CTCF and EBNA1 at sites of active transcription or DNA replication initiation. Our findings support a model where CTCF delineates multiple domains within the LCR and regulates interactions between these domains that correlate with changes in gene expression.
Crystal Structures of Major Envelope Proteins VP26 and VP28 from White Spot Syndrome Virus Shed Light on Their Evolutionary Relationship
Authors: Tang Xuhua , Wu Jinlu , Sivaraman J. , Hew Choy Leong 
Published: April 2007

ABSTRACT
White spot syndrome virus (WSSV) is a virulent pathogen known to infect various crustaceans. It has bacilliform morphology with a tail-like appendage at one end. The envelope consists of four major proteins. Envelope structural proteins play a crucial role in viral infection and are believed to be the first molecules to interact with the host. Here, we report the localization and crystal structure of major envelope proteins VP26 and VP28 from WSSV at resolutions of 2.2 and 2.0 Å, respectively. These two proteins alone account for approximately 60% of the envelope, and their structures represent the first two structural envelope proteins of WSSV. Structural comparisons among VP26, VP28, and other viral proteins reveal an evolutionary relationship between WSSV envelope proteins and structural proteins from other viruses. Both proteins adopt β-barrel architecture with a protruding N-terminal region. We have investigated the localization of VP26 and VP28 using immunoelectron microscopy. This study suggests that VP26 and VP28 are located on the outer surface of the virus and are observed as a surface protrusion in the WSSV envelope, and this is the first convincing observation for VP26. Based on our studies combined with the literature, we speculate that the predicted N-terminal transmembrane region of VP26 and VP28 may anchor on the viral envelope membrane, making the core β-barrel protrude outside the envelope, possibly to interact with the host receptor or to fuse with the host cell membrane for effective transfer of the viral infection. Furthermore, it is tempting to extend this host interaction mode to other structural viral proteins of similar structures. Our finding has the potential to extend further toward drug and vaccine development against WSSV.
MEK1/2 Inhibitors Block Basal and Transforming Growth Factor β1-Stimulated JC Virus Multiplication
Authors: Ravichandran Veerasamy , Jensen Peter N. , Major Eugene O. 
Published: April 2007

ABSTRACT
The multiplication of the human neurotropic polyomavirus JC virus (JCV) is regulated by cell membrane receptors and nuclear transcription factors. Signaling pathways also play a role in determining the extent to which JCV can productively infect cells. These data show that constitutively active MEK1 protein (CA-MEK1), overexpressed in cultures of human glia, supports a substantial increase in late JCV protein (Vp-1) synthesis. The specificity of this pathway was indicated by no significant enhancement of JCV multiplication through activation of other components of mitogen-activated protein kinase pathways such as p38, Jun N-terminal protein kinase, and protein kinase A. Further evidence supporting the importance of signaling in JCV infection came from addition of transforming growth factor β1 (TGF-β1), which stimulated a 200% increase of Vp-1 expression. Specific MEK1/2 inhibitors, flavenoid PD98059 and U0126, decreased the basal and TGF-β1-stimulated Vp-1 expression by 95% or more. TGF-β1 is known to phosphorylate/activate Smad DNA binding proteins that could subsequently bind or increase binding to JCV promoter sequences, linking the effects of signaling with JCV transcriptional regulation. The effectiveness with which MEK1/2 inhibitors block JCV multiplication provides insight that may contribute to development of compounds directed against JCV.
Biological and Immunological Relations among Human Parvovirus B19 Genotypes 1 to 3
Authors: Ekman Anna , Hokynar Kati , Kakkola Laura , Kantola Kalle , Hedman Lea , Bondén Heidi , Gessner Matthias , Aberham Claudia , Norja Päivi , Miettinen Simo , Hedman Klaus , Söderlund-Venermo Maria 
Published: April 2007

ABSTRACT
The human parvovirus B19 is now divided into three genotypes: type 1 (prototype), type 2 (A6- and LaLi-like), and type 3 (V9-like). In overall DNA sequence, the three virus types differ by ∼10%. The most striking DNA dissimilarity, of >20%, is observed within the p6 promoter region. Because of the scarcity of data on the biological activities and pathogenetic potentials of virus types 2 and 3, we examined the functional characteristics of these virus types. We found the activities of the three p6 promoters to be of equal strength and to be most active in B19-permissive cells. Virus type 2 capsid protein VP2, alone or together with VP1, was expressed with the baculovirus system and was shown to assemble into icosahedral parvovirus-like particles, which were reactive in the hemagglutination assay. Furthermore, sera containing DNA of any of the three B19 types were shown to hemagglutinate. The infectivities of these sera were examined in two B19-permissive cell lines. Reverse transcription-PCR revealed synthesis of spliced B19 mRNAs, and immunofluorescence verified the production of NS and VP proteins in the infected cells. All three genotypes showed similar functional characteristics in all experiments performed, showing that the three virus types indeed belong to the same species, i.e., human parvovirus B19. Additionally, the antibody activity in sera from B19 type 1- or type 2-infected subjects (long-term immunity) was examined with homo- and heterologous virus-like particles. Cross-reactivity of 100% was observed, indicating that the two B19 genotypes comprise a single serotype.
Identification of a Novel C-Terminal Cleavage of Crimean-Congo Hemorrhagic Fever Virus PreG
N
That Leads to Generation of an NS
M
Protein
Authors: Altamura Louis A. , Bertolotti-Ciarlet Andrea , Teigler Jeffrey , Paragas Jason , Schmaljohn Connie S. , Doms Robert W. 
Published: April 2007

ABSTRACT

The structural glycoproteins of Crimean-Congo hemorrhagic fever virus (CCHFV; genus
Nairovirus
, family
Bunyaviridae
) are derived through endoproteolytic cleavage of a 1,684-amino-acid M RNA segment-encoded polyprotein. This polyprotein is cotranslationally cleaved into the PreG
N
and PreG
C
precursors, which are then cleaved by SKI-1 and a SKI-1-like protease to generate the N termini of G
N
and G
C
, respectively. However, the resulting polypeptide defined by the N termini of G
N
and G
C
is predicted to be larger (58 kDa) than mature G
N
(37 kDa). By analogy to the topologically similar M segment-encoded polyproteins of viruses in the
Orthobunyavirus
genus, the C-terminal region of PreG
N
that contains four predicted transmembrane domains may also contain a nonstructural protein, NS
M
. To characterize potential PreG
N
C-terminal cleavage events, a panel of epitope-tagged PreG
N
truncation and internal deletion mutants was developed. These constructs allowed for the identification of a C-terminal endoproteolytic cleavage within, or very proximal to, the second predicted transmembrane domain following the G
N
ectodomain and the subsequent generation of a C-terminal fragment. Pulse-chase experiments showed that PreG
N
C-terminal cleavage occurred shortly after synthesis of the precursor and prior to generation of the G
N
glycoprotein. The resulting fragment trafficked to the Golgi compartment, the site of virus assembly. Development of an antiserum specific to the second cytoplasmic loop of PreG
N
allowed detection of cell-associated NS
M
proteins derived from transient expression of the complete CCHFV M segment and also in the context of virus infection.
The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area
Authors: Monteiller Claire , Tran Lang , MacNee William , Faux Steve , Jones Alan , Miller Brian , Donaldson Ken 
Published: April 2007

Objective:Rats exposed to high airborne mass concentrations of low-solubility low-toxicity particles (LSLTP) have been reported to develop lung disease such as fibrosis and lung cancer. These particles are regulated on a mass basis in occupational settings, but mass might not be the appropriate metric as animal studies have shown that nanoparticles (ultrafine particles) produce a stronger adverse effect than fine particles when delivered on an equal mass basis.Methods:This study investigated whether the surface area is a better descriptor than mass of LSLTP of their ability to stimulate pro-inflammatory responses in vitro. In a human alveolar epithelial type II-like cell line, A549, we measured interleukin (IL)-8 mRNA, IL8 protein release and glutathione (GSH) depletion as markers of pro-inflammatory effects and oxidative stress after treatment with a range of LSLTP (fine and nanoparticles) and DQ12 quartz, a particle with a highly reactive surface.Results:In all the assays, nanoparticle preparations of titanium dioxide (TiO2-np) and of carbon black (CB-np) produced much stronger pro-inflammatory responses than the same mass dose of fine TiO2and CB. The results of the GSH assay confirmed that oxidative stress was involved in the response to all the particles, and two ultra-fine metal dusts (cobalt and nickel) produced GSH depletion similar to TiO2-np, for similar surface-area dose. As expected, DQ12 quartz was more inflammatory than the low toxicity dusts, on both a mass and surface-area basis.Conclusion:Dose–response relationships observed in the in vitro assays appeared to be directly comparable with dose–response relationships in vivo when the doses were similarly standardised. Both sets of data suggested a threshold in dose measured as surface area of particles relative to the surface area of the exposed cells, at around 1–10 cm2/cm2.These findings are consistent with the hypothesis that surface area is a more appropriate dose metric than mass for the pro-inflammatory effects of LSLTP in vitro and in vivo, and consequently that the high surface area of nanoparticles is a key factor in their inflammogenicity.
A simple diagnostic model for ruling out pneumoconiosis among construction workers
Authors: Suarthana Eva , Moons Karel G M , Heederik Dick , Meijer Evert 
Published: April 2007

Background:Construction workers exposed to silica-containing dust are at risk of developing silicosis even at low exposure levels. Health surveillance among these workers is commonly advised but the exact diagnostic work-up is not specified and therefore may result in unnecessary chestxray investigations.Aim:To develop a simple diagnostic model to estimate the probability of an individual worker having pneumoconiosis from questionnaire and spirometry results, in order to accurately rule out workers without pneumoconiosis.Methods:The study was performed using cross-sectional data of 1291 Dutch natural stone and construction workers with potentially high quartz dust exposure. A multivariable logistic regression model was developed using chestxray with ILO profusion category ⩾1/1 as the reference standard. The model’s calibration was evaluated with the Hosmer–Lemeshow test; the discriminative ability was determined by calculating the area under the receiver operating characteristic curve (ROC area). Internal validity of the final model was assessed by a bootstrapping procedure. For clinical application, the diagnostic model was transformed into an easy-to-use score chart.Results:Age 40 years or older, current smoker, high-exposure job, working 15 years or longer in the construction industry, “feeling unhealthy” and FEV1were independent predictors in the diagnostic model. The model showed good calibration (a non-significant Hosmer–Lemeshow test) and discriminative ability (ROC area 0.81, 95% CI 0.74 to 0.85). Internal validity was reasonable; the optimism corrected ROC area was 0.76. By using a cut-off point with a high negative predictive value the occupational physician can efficiently detect a large proportion of workers with a low probability of having pneumoconiosis and exclude them from unnecessaryxray investigations.Conclusions:This diagnostic model is an efficient and effective instrument to rule out pneumoconiosis among construction workers. Its use in health surveillance among these workers can reduce the number of redundantxray investigations.
Short-term effects of ozone air pollution on ischaemic stroke occurrence: a case-crossover analysis from a 10-year population-based study in Dijon, France
Authors: Henrotin J B , Besancenot J P , Bejot Y , Giroud M 
Published: April 2007

Objective:To evaluate the association between air pollutants and the occurrence of acute stroke from 10-year population-based study.Methods:The daily stroke count was obtained from Dijon Stroke Register between March 1994 and December 2004. The register recorded all first-ever strokes among residents of Dijon (150 000 inhabitants) in France, using standard diagnostic criteria. Pollutant concentrations (SO2, CO, NO2,O3and PM10) were measured hourly. A bi-directional case-crossover design was used to examine the association between air pollutant and stroke onset. The conditional logistic regression model included the meteorological parameters (temperature, relative humidity), influenza epidemics and holidays.Results:The authors collected 493 large artery infarcts, 397 small artery infarcts, 530 cardio-embolic infarcts, 67 undeterminate infarcts, 371 transient ischaemic attacks and 220 haemorrhagic strokes. For single-pollutant model and for a 10 mg/m3increase of O3exposure, a positive association was observed only in men, over 40 years of age, between ischaemic stroke occurrence and O3levels with 1-day lag, (OR 1.133, 95% CI 1.052 to 1.220) and 0-day lag (OR 1.058, 95% CI 0.987 to 1.134). No significant associations were found for haemorrhagic stroke. In two-pollutant models, the effects of O3remained significant after each of the other pollutants were included in the model, in particular with PM10. A significant association was observed for ischaemic strokes of large arteries (p = 0.02) and for transient ischaemic attacks (p = 0.01). Moreover, the authors found an exposure-response relations between O3exposure and ischaemic stroke (test for trend, p = 0.01). An increase in association in men with several cardiovascular risk factors (smoker, dyslipidemia and hypertension) was also observed.Conclusion:These observational data argue for an association between ischaemic stroke occurrence and O3pollution levels; these results still need to be confirmed by other studies.
Long-term use of cellular phones and brain tumours: increased risk associated with use for ⩾10 years
Authors: Hardell Lennart , Carlberg Michael , Söderqvist Fredrik , Mild Kjell Hansson , Morgan L. Lloyd 
Published: April 2007

Aim:To evaluate brain tumour risk among long-term users of cellular telephones.Methods:Two cohort studies and 16 case–control studies on this topic were identified. Data were scrutinised for use of mobile phone for ⩾10 years and ipsilateral exposure if presented.Results:The cohort study was of limited value due to methodological shortcomings in the study. Of the 16 case–control studies, 11 gave results for ⩾10 years’ use or latency period. Most of these results were based on low numbers. An association with acoustic neuroma was found in four studies in the group with at least 10 years’ use of a mobile phone. No risk was found in one study, but the tumour size was significantly larger among users. Six studies gave results for malignant brain tumours in that latency group. All gave increased odd ratios (OR), especially for ipsilateral exposure. In a meta-analysis, ipsilateral cell phone use for acoustic neuroma was OR = 2.4 (95% CI 1.1 to 5.3) and OR = 2.0, (1.2 to 3.4) for glioma using a tumour latency period of ⩾10 years.Conclusions:Results from present studies on use of mobile phones for ⩾10 years give a consistent pattern of increased risk for acoustic neuroma and glioma. The risk is highest for ipsilateral exposure.
Environment parameters and basic functions for floating-point computation
Authors: Brown W. S. , Feldman S. I. 
Published: April 2007

This paper presents a language-independent proposal for environment parameters and basic functions for floating-point computation, and suggests a specific representation in terms of generic functions for Fortran 77. The environment parameters were originally introduced in 1967 by Forsythe and Moler [1], who attributed the essentials of their theory to Wilkinson [2]. These parameters are also used in the PORT mathematical subroutine library [3], with precise definitions in terms of a more recent model of floating-point computation [4], and a similar set has been proposed by the IFIP Working on Numerical Software [5]. Three of the basic functions are taken from a proposal by Ford, Reid, and Smith [6], but redefined in terms of the parameters and the model to provide a firm theoretical foundation. The other three basic functions can be expressed in terms of these, but we feel they should be provided separately for convenience.
The stated purpose of the model is to capture the fundamental concepts of floating-point computation in a small set of parameters and a small set of axioms. In this paper we extend the earlier work by proposing basic functions to analyze, synthesize, and scale floating-point numbers, and to provide sharp measures of roundoff error.
Programmable formatting of program text
Authors: Dritz Kenneth W. 
Published: April 2007

The TAMPR System originated as an approach to the problem of automating the routine modifications of Fortran source programs required to adapt them to a variety of uses or environments [1]**. Overall, the system accomplishes such modifications by applying transformations to Fortran programs at the source level. But the process differs markedly, in detail, from string-based editing or macro expansion. Three steps are involved:
(1) A Fortran source program is processed by the TAMPR Recognizer, yielding essentially a parse tree called the abstract form.
(2) The Transformation Interpreter applies IGT's (Intragrammatical Transformations) to the abstract form as tree operations [2].
(3) The abstract form is then reconverted to source program form by the Formatter.
By ensuring that the transformations are applied only to the correct syntactic entities and only in the intended contexts, the use of the abstract form greatly simplifies establishing the reliability of the overall process.
The programming language EFL
Authors: Feldman S. I. 
Published: April 2007

EFL is a comprehensive language designed to make it easy to write portable, understandable programs. It provides a rich set of data types and structures, a convenient operator set, and good control flow forms. The lexical form is easy to type and to read.
EFL was originated by A. D. Hall. The current author completed the design of the language and wrote the current compiler. Whenever possible, EFL uses the same forms that Ratfor [1] does; in this sense EFL may be viewed as a superset of Ratfor. EFL is a well-defined language; this distinguishes it from most “Fortran preprocessors” which only add simple flow of control constructs to Fortran.
The complexity of homomorphism and constraint satisfaction problems seen from the other side
Authors: Grohe Martin 
Published: April 2007

We give a complexity theoretic classification of homomorphism problems for graphs and, more generally, relational structures obtained by restricting the left hand side structure in a homomorphism. For every class C of structures, let HOM(C,−) be the problem of deciding whether a given structure A ∈C has a homomorphism to a given (arbitrary) structure ß. We prove that, under some complexity theoretic assumption from parameterized complexity theory, HOM(C,−) is in polynomial time if and only if C has bounded tree width modulo homomorphic equivalence.
Translated into the language of constraint satisfaction problems, our result yields a characterization of the tractable structural restrictions of constraint satisfaction problems. Translated into the language of database theory, it implies a characterization of the tractable instances of the evaluation problem for conjunctive queries over relational databases.
Polymorphic higher-order recursive path orderings
Authors: Jouannaud Jean-Pierre , Rubio Albert 
Published: April 2007

This article extends the termination proof techniques based on reduction orderings to a higher-order setting, by defining a family of recursive path orderings for terms of a typed lambda-calculus generated by a signature of polymorphic higher-order function symbols. These relations can be generated from two given well-founded orderings, on the function symbols and on the type constructors. The obtained orderings on terms are well founded, monotonic, stable under substitution and include β-reductions. They can be used to prove the strong normalization property of higher-order calculi in which constants can be defined by higher-order rewrite rules using first-order pattern matching. For example, the polymorphic version of Gödel's recursor for the natural numbers is easily oriented. And indeed, our ordering is polymorphic, in the sense that a single comparison allows to prove the termination property of all monomorphic instances of a polymorphic rewrite rule. Many nontrivial examples are given that exemplify the expressive power of these orderings. All have been checked by our implementation.
This article is an extended and improved version of Jouannaud and Rubio [1999]. Polymorphic algebras have been made more expressive than in our previous framework. The intuitive notion of a polymorphic higher-order ordering has now been made precise. The higher-order recursive path ordering itself has been made much more powerful by replacing the congruence on types used there by an ordering on types satisfying some abstract properties. Besides, using a restriction of Dershowitz's recursive path ordering for comparing types, we can integrate both orderings into a single one operating uniformly on both terms and types.