bluuebunny/crossref_metadata_2025_split huggingface dataset:
X Box Binding Protein XBP-1s Transactivates the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) ORF50 Promoter, Linking Plasma Cell Differentiation to KSHV Reactivation from Latency
Authors: Wilson Sam J. , Tsao Edward H. , Webb Benjamin L. J. , Ye Hongtao , Dalton-Griffin Lucy , Tsantoulas Christoforos , Gale Catherine V. , Du Ming-Qing , Whitehouse Adrian , Kellam Paul 
Published: October 2007

ABSTRACT
Reactivation of lytic replication from viral latency is a defining property of all herpesviruses. Despite this, the authentic physiological cues for the latent-lytic switch are unclear. Such cues should ensure that viral lytic replication occurs under physiological conditions, predominantly in sites which facilitate transmission to permissive uninfected cells and new susceptible hosts. Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with the B-cell neoplasm primary effusion lymphoma (PEL), in which the virus remains latent. We have previously shown that PEL cells have the gene expression profile and immunophenotype of cycling preplasma cells (plasmablasts). Here, we show that the highly active spliced isoform of plasma cell transcription factor X box binding protein 1 (XBP-1s) is a lytic switch for KSHV. XBP-1s is normally absent in PEL, but the induction of endoplasmic reticulum stress leads to XBP-1s generation, plasma cell-like differentiation, and lytic reactivation of KSHV. XBP-1s binds to and activates the KSHV immediate-early gene ORF50 and synergizes with the ORF50 gene product RTA to induce a full lytic cycle. These data suggest that KSHV remains latent until B-cell terminal differentiation into plasma cells, the transcriptional environment of which provides the physiological “lytic switch” through XBP-1s. This links B-cell terminal differentiation to KSHV lytic reactivation.
A Novel Zinc-Binding Domain Is Essential for Formation of the Functional Junín Virus Envelope Glycoprotein Complex
Authors: York Joanne , Nunberg Jack H. 
Published: October 2007

ABSTRACT

The envelope glycoprotein of the Junín arenavirus (GP-C) mediates entry into target cells through a pH-dependent membrane fusion mechanism. Unlike other class I viral fusion proteins, the mature GP-C complex retains a cleaved, 58-amino-acid signal peptide (SSP) as an essential subunit, required both for trafficking of GP-C to the cell surface and for the activation of membrane fusion. SSP has been shown to associate noncovalently in GP-C via the cytoplasmic domain (CTD) of the transmembrane fusion subunit G2. In this report we investigate the molecular basis for this intersubunit interaction. We identify an invariant series of six cysteine and histidine residues in the CTD of G2 that is essential for incorporation of SSP in the GP-C complex. Moreover, we show that a CTD peptide fragment containing His-447, His-449, and Cys-455 specifically binds Zn
2+
at subnanomolar concentrations. Together, these results suggest a zinc finger-like domain structure in the CTD of G2. We propose that the remaining residues in the series (His-459, Cys-467, and Cys-469) form an intersubunit zinc-binding center that incorporates Cys-57 of SSP. This unusual motif may act to retain SSP in the GP-C complex and position the ectodomain loop of SSP for its role in modulating membrane fusion activity. The unique tripartite organization of GP-C could provide novel molecular targets for therapeutic intervention in arenaviral disease.
Type I Interferons Are Essential in Controlling Neurotropic Coronavirus Infection Irrespective of Functional CD8 T Cells
Authors: Ireland Derek D. C. , Stohlman Stephen A. , Hinton David R. , Atkinson Roscoe , Bergmann Cornelia C. 
Published: October 2007

ABSTRACTNeurotropic coronavirus infection induces expression of both beta interferon (IFN-β) RNA and protein in the infected rodent central nervous system (CNS). However, the relative contributions of type I IFN (IFN-I) to direct, cell-type-specific virus control or CD8 T-cell-mediated effectors in the CNS are unclear. IFN-I receptor-deficient (IFNAR−/−) mice infected with a sublethal and demyelinating neurotropic virus variant and those infected with a nonpathogenic neurotropic virus variant both succumbed to infection within 9 days. Compared to wild-type (wt) mice, replication was prominently increased in all glial cell types and spread to neurons, demonstrating expanded cell tropism. Furthermore, increased pathogenesis was associated with significantly enhanced accumulation of neutrophils, tumor necrosis factor alpha, interleukin-6, chemokine (C-C motif) ligand 2, and IFN-γ within the CNS. The absence of IFN-I signaling did not impair induction or recruitment of virus-specific CD8 T cells, the primary adaptive mediators of virus clearance in wt mice. Despite similar IFN-γ-mediated major histocompatibility complex class II upregulation on microglia in infected IFNAR−/−mice, class I expression was reduced compared to that on microglia in wt mice, suggesting a synergistic role of IFN-I and IFN-γ in optimizing class I antigen presentation. These data demonstrate a critical direct antiviral role of IFN-I in controlling virus dissemination within the CNS, even in the presence of potent cellular immune responses. By limiting early viral replication and tropism, IFN-I controls the balance of viral replication and immune control in favor of CD8 T-cell-mediated protective functions.
The Rabies Virus Glycoprotein Receptor p75
NTR
Is Not Essential for Rabies Virus Infection
Authors: Tuffereau Christine , Schmidt Klaus , Langevin Christelle , Lafay Florence , Dechant Georg , Koltzenburg Martin 
Published: October 2007

ABSTRACT

Rabies virus glycoprotein (RVG) is known to be the only factor that mediates rabies infection. The neurotrophin receptor (p75
NTR
), through its cysteine-rich domain 1, is a specific receptor for RVG and neutralizes virus infectivity, but its role in virus infection has remained obscure. We used adult mouse dorsal root ganglion (DRG) neurons as a model to study the role of p75
NTR
in RV infection of primary neurons. We show that RV infects around 20% of DRG neurons, of which more than 80% are p75
NTR
positive, have large diameters, and are capsaicin insensitive. Surprisingly, RV binding and infection are absent in about half of the p75
NTR
-expressing DRG neurons which have small diameters and are often capsaicin sensitive. This indicates that p75
NTR
is not sufficient to mediate RV interaction in sensory neurons. The rate and specificity of neural infection are unchanged in RV-infected p75
NTRExonIV−/−
mice that lack all extracellular receptor domains and in wild-type mice infected with two independent RV mutants that lack p75
NTR
binding. Accordingly, the mortality rate is unchanged in the absence of RV-p75
NTR
interaction. We conclude that although p75
NTR
is a receptor for soluble RVG in transfected cells of heterologous expression systems, an RVG-p75
NTR
interaction is not necessary for RV infection of primary neurons. This means that other receptors are required to mediate RV infection in vivo and in vitro.
Linking forests and economic well-being: a four-quadrant approach
Authors: Wang Sen , DesRoches C. Tyler , Sun Lili , Stennes Brad , Wilson Bill , Cornelis van Kooten   G. 
Published: October 2007

This paper has three main objectives: (i) to investigate whether the four-quadrant approach introduced by J.S. Maini reveals a useful typology for grouping countries by gross domestic product (GDP) and forest cover per capita, (ii) to determine if the framework can enhance our understanding of the relationship between forest cover and GDP per capita, and (iii) to investigate why countries in the four-quadrant world occupy different quadrants and to determine the principal factors affecting country movement across and within the individual quadrants. The examination reveals that countries can be classified into four broad categories and that GDP and forest cover per capita have a low but consistent level of negative association. After regressing economic, institutional, social capital, and other variables on a country’s occupancy and movement in the four-quadrant world, the results suggest that countries in each quadrant share different characteristics and that factors underlying country movement vary according to the quadrant being observed. Overall, countries with less corruption and higher education are likely to experience increases in both forest cover and GDP per capita, while countries exporting a significant proportion of forest products have a reduced probability of increasing both variables.
Ground-layer response to group selection with legacy-tree retention in a managed northern hardwood forest
Authors: Shields Joshua M. , Webster Christopher R. 
Published: October 2007

We examined the effects of group selection with legacy-tree retention on ground-layer or understory diversity and composition in an uneven-aged northern hardwood forest in the Upper Peninsula of Michigan. We sampled 20 reference plots in the surrounding forest matrix and 49 openings with radii of 0.5 (n = 16), 0.75 (n = 17), and 1.0 (n = 16) times mean canopy tree height (22 m). Resultant opening areas were 321 ± 16 (mean ± SEs), 697 ± 21, and 1256 ± 39 m2, respectively. Each opening contained a centrally located legacy tree. Two years after harvesting, ground-layer diversity was significantly higher in openings than on reference plots (p < 0.05) because of an influx of early seral, wetland, and weedy exotic species. The importance of aggressive ruderals (i.e., Carex ormostachya Wieg. and Rubus idaeus subsp. strigosus (Michx.) Focke) increased significantly (p < 0.001) with increasing opening area. Although the importance and cover of several late-seral species were lower in openings compared with the forest matrix, few species found in the matrix were wholly absent from the openings. These results suggest that ground-layer plant communities in managed northern hardwood forests may display a high degree of resilience to intermediate-intensity disturbances.
WATT MATTERS MOST? DESIGN SPACE EXPLORATION OF HIGH-PERFORMANCE MICROPROCESSORS FOR POWER-PERFORMANCE EFFICIENCY
Authors: TRANCOSO PEDRO 
Published: October 2007

Computer systems have evolved significantly in the last years leading to high-performance systems. This, however, has come with a cost of large power dissipation. As such, power-awareness has become a major factor in processor design. Therefore, it is important to have a complete understanding of the power and performance behavior of all processor components. In order to achieve this, the current work presents a comprehensive analysis of power-performance efficiency for different high-end microarchitecture configurations using three different workloads: multimedia, scientific, and database. The objectives of this work are: (1) to analyze and compare the power-performance efficiency for different workloads; (2) to present a sensitivity analysis for the microarchitecture parameters in order to identify which ones are more sensitive to changes in terms of power-performance efficiency; and (3) to propose power-performance efficient configurations for each workload. The simulation results show that the multimedia workload is the one achieving the highest efficiency but the database workload is the most sensitive to parameter changes. In addition, the results also show that the parameter sensitivity depends significantly on the workload. While the issue width and clock frequency present very high sensitivity across all workloads (approximately 100%), for the database workload, the first-level instruction cache size shows an even higher sensitivity (149%). The correct configuration of these microarchitecture parameters is essential. A careless configuration of a single parameter from a baseline setup may result in a loss of the power-performance efficiency of up to 99%. Finally, carefully tuning multiple parameters simultaneously may result in gains up to 154% over the power-performance efficiency of the baseline configuration.
MATHEMATICAL ANALYSIS AND CHALLENGES ARISING FROM MODELS OF TUMOR GROWTH
Authors: FRIEDMAN AVNER 
Published: October 2007

In the last four decades, various cancer models have been developed in which the evolution of the densities of cells (abnormal, normal, or dead) and the concentrations of biochemical species are described in terms of differential equations. In this paper, we deal with tumor models in which the tumor occupies a well-defined region in space; the boundary of this region is held together by the forces of cell-to-cell adhesion. We shall refer to such tumors as "solid" tumors, although they may sometimes consist of fluid-like tissue, such as in the case of brain tumors (e.g. gliomas) and breast tumors. The most common class of solid tumors is carcinoma: a cancer originating from epithelial cells, that is, from the closely packed cells which align the internal cavities of the body.Models of solid tumors must take spatial effects into account, and are therefore described in terms of partial differential equations (PDEs). They also need to take into account the fact that the tumor region is changing in time; in fact, the tumor region, say Ω(t), and its boundary Γ(t), are unknown in advance. Thus one needs to determine both the unknown "free boundary" Γ(t) together with the solution of the PDEs in Ω(t). These types of problems are called free boundary problems. The models described in this paper are free boundary problems, and our primary interest is the spatial/geometric features of the free boundary. Some of the basic questions we shall address are: What is the shape of the free boundary? How does the free boundary behave as t → ∞? Does the tumor volume increase or shrink as t → ∞? Under what conditions does the tumor eventually become dormant? Finally, we shall explore the dependence of the free boundary on some biological parameters, and this will give rise to interesting bifurcation phenomena.The structure of the paper is as follows. In Secs. 1 and 2 we consider models in which all the cells are of one type, they are all proliferating cells. The tissue is modeled either as a porous medium (in Sec. 1) or as a fluid medium (in Sec. 2). The models are extended in Secs. 3 and 4 to include three types of cells: proliferating, quiescent, and dead. Finally, in Sec. 5 we outline a general multiphase model that includes gene mutations.
POROUS MEDIUM FLOW IN A TUBE: TRAVELING WAVES AND KPP BEHAVIOR
Authors: VÁZQUEZ JUAN LUIS 
Published: October 2007

We study the long-time behavior of the solutions of the Porous Medium Equation ut = Δ um, m > 1, posed in a tube Ω = ℝ × D, where D is a bounded domain in ℝn, and with homogeneous Dirichlet conditions on the lateral boundary. We show that the asymptotic behavior of general nonnegative solutions follows the KPP pattern in suitable rescaled variables. We proceed as follows: we pass to the renormalized problem and show that this problem admits a wave solution that travels along the tube with constant speed with respect to the new time (which is logarithmic in the old time scale). This solution has a bounded free boundary as a forward front. We also show that the universal asymptotic pattern for solutions with compactly supported data is described in the renormalized form by two of these traveling waves going out in different directions, joined by a stationary profile in the middle region. We compare this situation with the heat equation case ut = Δu that behaves quite differently.
Blood Markers for Early Detection of Colorectal Cancer: A Systematic Review
Authors: Hundt Sabrina , Haug Ulrike , Brenner Hermann 
Published: October 2007

AbstractBackground: Despite different available methods for colorectal cancer (CRC) screening and their proven benefits, morbidity, and mortality of this malignancy are still high, partly due to low compliance with screening. Minimally invasive tests based on the analysis of blood specimens may overcome this problem. The purpose of this review was to give an overview of published studies on blood markers aimed at the early detection of CRC and to summarize their performance characteristics.Method: The PUBMED database was searched for relevant studies published until June 2006. Only studies with more than 20 cases and more than 20 controls were included. Information on the markers under study, on the underlying study populations, and on performance characteristics was extracted. Special attention was given to performance characteristics by tumor stage.Results: Overall, 93 studies evaluating 70 different markers were included. Most studies were done on protein markers, but DNA markers and RNA markers were also investigated. Performance characteristics varied widely between different markers, but also between different studies using the same marker. Promising results were reported for some novel assays, e.g., assays based on SELDI-TOF MS or MALDI-TOF MS, for some proteins (e.g., soluble CD26 and bone sialoprotein) and also for some genetic assays (e.g., L6 mRNA), but evidence thus far is restricted to single studies with limited sample size and without further external validation.Conclusions: Larger prospective studies using study populations representing a screening population are needed to verify promising results. In addition, future studies should pay increased attention to the potential of detecting precursor lesions. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1935–53)
Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome
Authors: Pelekanou Vassiliki , Kampa Marilena , Kafousi Maria , Dambaki Konstantina , Darivianaki Katerina , Vrekoussis Thomas , Sanidas Elias , Tsiftsis Dimitrios D. , Stathopoulos Efstathios N. , Castanas Elias 
Published: October 2007

Abstract
Autocrine/paracrine erythropoietin (EPO) action, promoting cell survival and mediated by its receptor (EPOR) in various solid tumors, including breast carcinoma, questions about the prognostic and therapeutic interest of this system. The expression of EPO/EPOR is steroid dependent in some tissues; however, a clear relationship of EPO/EPOR and steroid receptors in breast cancer has not been established thus far. Recently, the field of steroid receptors has expanded, including rapid effects mediated by membrane-associated receptors, regulating cell survival or apoptosis. The aim of this study was to evaluate EPO/EPOR and membrane-associated steroid receptor expression in breast carcinoma, in view of their prognostic significance, compared with other established markers [estrogen receptor (ER)-progesterone receptor (PR) status and Her2 expression] and hypoxia-induced factor 1 nuclear localization in 61 breast cancer specimens followed for ≤90 months. We report that EPO-EPOR were expressed in 80% and 84% of samples, although 8% and 2% of nontumoral fields expressed EPO/EPOR too. Membrane-associated receptors for estrogen (mER), progesterone (mPR), and androgen (mAR) were expressed in 96%, 94%, and 93% of cases. Significant correlations between EPO-hypoxia-induced factor 1α, mER-ER, mER-EPO, mAR-EPOR, and mER-mPR-Her2 were found. Finally, EPO, EPOR, and mAR are inversely related to disease-free and overall survival. However, in view of the above correlations, we conclude that EPO/EPOR and membrane steroid receptors are not independent prognostic markers as they are closely related to other established markers. In contrast, they may represent possible new therapeutic targets. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2016–23)
Endogenous Optical Biomarkers of Ovarian Cancer Evaluated with Multiphoton Microscopy
Authors: Kirkpatrick Nathaniel D. , Brewer Molly A. , Utzinger Urs 
Published: October 2007

Abstract
Purpose: Among gynecologic cancers, ovarian cancer is the second most common and has the highest mortality. Currently, there is no accurate early diagnostic technique for ovarian cancer. Furthermore, little is understood regarding the early progression of this disease. We have imaged multiphoton interactions of endogenous tissue constituents from normal and abnormal ovarian biopsies that were kept viable during transport from the operating room and microscopy.
Experimental Design: The ovarian surface and underlying stroma were assessed with two-photon excited fluorescence (2PEF) and second harmonic generation (SHG). High-resolution, optically sectioned images were analyzed for epithelial morphology based on 2PEF and collagen density and structural integrity based on SHG. Additionally, multiwavelength 2PEF provided an estimation of the cellular redox ratio of epithelial cells.
Results: Normal tissue exhibited a uniform epithelial layer with highly structured collagen in the stroma, whereas abnormal tissue exhibited varied epithelium with large cells and substantial quantitative changes to the collagen structure. Samples from patients at high risk for developing ovarian cancer (based on their personal/family history of cancer) exhibited highly variable cellular redox ratios and changes in collagen structure that trended toward cancer samples.
Conclusion: This study highlights differences in endogenous signals in viable ovarian biopsies based on quantitative collagen structural changes and redox ratio estimates that may lead to improved detection and further insights in ovarian cancer, particularly in the early stages of the disease. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2048–55)
Association of Physical Activity with Reproductive Hormones: The Penn Ovarian Aging Study
Authors: Schmitz Kathryn H. , Lin Hui , Sammel Mary D. , Gracia Clarissa R. , Nelson Deborah B. , Kapoor Shiv , DeBlasis Tracey L. , Freeman Ellen W. 
Published: October 2007

Abstract
Background: Physical activity is associated with reduced risk for breast cancer, perhaps through reductions in circulating reproductive hormones (estrogens and androgens). There may also be a role for physical activity in regulating menopausal symptoms. Few studies have examined associations of physical activity on hormone levels. None have examined the potential effect of the menopausal transition on the associations between physical activity and reproductive hormone levels.
Materials and Methods: Data from the Penn Ovarian Aging Study were used for this analysis. Self-reported physical activity was assessed in 391 women up to four times over 10 years and extending across the menopausal transition. Other assessments included reproductive hormones via RIA (estradiol, luteinizing hormone, follicle-stimulating hormone, testosterone, DHEA sulfate), body weight, and height. Multivariate repeated measures regression models were developed to compare reproductive hormone levels within physical activity tertiles, adjusting for age, follow-up time, smoking, and ethnicity.
Results: Activity level was inversely associated with estradiol in the subgroup in the late transition stage. Adjusted means for estradiol were 24.6 and 37.9, a relative difference of 54% in estradiol when comparing highest to lowest activity tertile (P = 0.02). Similarly, in this subgroup, there was an inverse association between physical activity and testosterone levels (means of 11.1 and 15.94 in the highest and lowest tertile, a 47% relative difference; P = 0.01). There were no significant associations of activity with any other reproductive hormone.
Conclusions: These results identify a particular window of the menopausal transition during which physical activity is associated with reduced estradiol and/or testosterone levels. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2042–7)