bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Transcription and DNA Replication by the Papillomavirus E8⁁E2C Protein Is Mediated by Interaction with Corepressor Molecules
Authors: Ammermann Ingo , Bruckner Markus , Matthes Frank , Iftner Thomas , Stubenrauch Frank
Published: March 2008

Papillomavirus genomes replicate as nuclear plasmids at a low copy number in undifferentiated keratinocytes. Papillomaviruses encode the E1 and E2 proteins that bind to the origin of replication and are required for the activation of replication. In addition to E2, several papillomaviruses express an E8⁁E2C protein, which is generated by alternative splicing and functions as a transcriptional repressor and inhibitor of the E1/E2-dependent replication of the viral origin. Previous analyses suggested that the E8 domain functions as a transferable repression domain. In this report we present evidence that the E8 domain is responsible for the interaction with cellular corepressor molecules such as histone deacetylases, the histone methyltransferase SETDB1, and the TRIM28/KAP-1/TIF1β/KRIP-1 protein. Whereas the interaction with histone deacetylases is involved only in transcriptional repression, the interaction with TRIM28/KAP-1/TIF1β/KRIP-1 contributes to the inhibition of E1/E2-dependent replication. The corepressor TRIM28/KAP-1/TIF1β/KRIP-1 has been described to be part of multicomponent complexes involved in transcriptional regulation and functions as a scaffold protein. Since neither histone deacetylases nor the histone methyltransferase SETDB1 appears to be involved in the inhibition of E1/E2-dependent replication, most likely the modification of non-histone proteins contributes to the replication repression activity of E8⁁E2C.
Identification of dysregulated genes in lymphocytes from children with Down syndrome
Authors: Sommer Cesar A. , Pavarino-Bertelli Erika C. , Goloni-Bertollo Eny M. , Henrique-Silva Flavio
Published: March 2008

The molecular mechanisms by which trisomy of human chromosome 21 disrupts normal development are not well understood. Global transcriptome studies attempting to analyze the consequences of trisomy in Down syndrome (DS) tissues have reported conflicting results, which have led to the suggestion that the analysis of specific tissues or cell types may be more productive. In the present study, we set out to analyze global changes of gene expression in lymphocytes from children with trisomy 21 by means of the serial analysis of gene expression (SAGE) methodology. Two SAGE libraries were constructed using pooled RNA of normal and Down syndrome children. Comparison between DS and normal profiles revealed that most of the transcripts were expressed at similar levels and functional classes of abundant genes were equally represented. Among the 242 significantly differentially expressed SAGE tags, several transcripts downregulated in DS code for proteins involved in T-cell and B-cell receptor signaling (e.g., PI3Kδ, RGS2, LY6E, FOS, TAGAP, CD46). The SAGE data and interindividual variability were validated by real-time quantitative PCR. Our results indicate that trisomy 21 induces a modest dysregulation of disomic genes that may be related to the immunological perturbations seen in DS.
Co-amplification of mitochondrial pseudogenes inCalomys musculinus(Rodentia, Cricetidae): a source of error in phylogeographic studies
Authors: González-Ittig Raúl E. , Gardenal Cristina N.
Published: March 2008

In a previous phylogeographic study of the rodent Calomys musculinus , 24 haplotypes of the mitochondrial DNA D-loop region were detected using the restriction fragment length polymorphism technique (PCR-RFLP). Seven percent of the individuals showed patterns in which the sum of the sizes of the restriction fragments exceeded the size of the original PCR product. In the present paper we analyze possible causes of these atypical haplotypes. PCR products were cloned, and two or three different clones from a single individual were detected by their RFLP patterns. Nine clones with different restriction patterns were selected for sequence analyses. A maximum parsimony phylogenetic analysis revealed two well-supported paraphyletic groups. One group comprised sequences showing low nucleotide divergence compared with the most common haplotypes detected in the phylogeographic study. The other group was basal to the three species of Calomys other than C. musculinus included in the study; the mutations in the short portion of the cytochrome b gene amplified corresponded to 12 amino acid substitutions. The results suggest that two independent insertions of mtDNA sequences into the nucleus occurred; these sequences would co-amplify in the PCR procedure. Identification of pseudogenes is crucial to obtain reliable reconstruction of the intraspecific genealogy in phylogeographic studies.
Identification of stably expressed quantitative trait loci for cooked rice elongation in non-Basmati varieties
Authors: Liu L. L. , Yan X. Y. , Jiang L. , Zhang W. W. , Wang M. Q. , Zhou S. R. , Shen Y. , Shen Y. Y. , Liu S. J. , Chen L. M. , Wang J. K. , Wan J. M.
Published: March 2008

The elongation of the cooked grain determines the cooking and eating quality of Basmati rice. The identification of stable quantitative trait loci (QTLs), especially those from non-Basmati types, will extend the genetic basis of the Basmati type and facilitate the breeding of high-quality varieties. A set of recombinant inbred lines derived from an indica × japonica hybrid was used to identify QTLs controlling the elongation ratio (ER), elongation index (EI), and water absorption (WA) of the cooked grain. Three ER QTLs on chromosomes 2, 4, and 12, two EI QTLs on chromosomes 2 and 5, and two WA QTLs on chromosomes 2 and 6 were detected. Four of these QTLs were validated using a set of established chromosome segment substitution lines. The genetic effect of qER-2 was explored in an analysis of segregating generations, using 8 newly developed simple sequence repeat markers. Two tightly linked loci (qER-2a and qER-2b) were identified on chromosome 2.
Integration ofBrassicaA genome genetic linkage map betweenBrassica napusandB. rapa
Authors: Suwabe Keita , Morgan Colin , Bancroft Ian
Published: March 2008

An integrated linkage map between B. napus and B. rapa was constructed based on a total of 44 common markers comprising 41 SSR (33 BRMS, 6 Saskatoon, and 2 BBSRC) and 3 SNP/indel markers. Between 3 and 7 common markers were mapped onto each of the linkage groups A1 to A10. The position and order of most common markers revealed a high level of colinearity between species, although two small regions on A4, A5, and A10 revealed apparent local inversions between them. These results indicate that the A genome of Brassica has retained a high degree of colinearity between species, despite each species having evolved independently after the integration of the A and C genomes in the amphidiploid state. Our results provide a genetic integration of the Brassica A genome between B. napus and B. rapa. As the analysis employed sequence-based molecular markers, the information will accelerate the exploitation of the B. rapa genome sequence for the improvement of oilseed rape.
Genetic structure of wild emmer wheat populations as reflected by transcribed versus anonymous SSR markers
Authors: Peleg Zvi , Fahima Tzion , Abbo Shahal , Krugman Tamar , Saranga Yehoshua
Published: March 2008

Simple sequence repeat (SSR) markers have become a major tool in population genetic analyses. The anonymous genomic SSRs (gSSRs) have been recently supplemented with expressed sequence tag (EST) derived SSRs (eSSRs), which represent the transcribed regions of the genome. In the present study, we used 8 populations of wild emmer wheat ( Triticum turgidum subsp. dicoccoides ) to compare the usefulness of the two types of SSR markers in assessing allelic diversity and population structure. gSSRs revealed significantly higher diversity than eSSRs in terms of average number of alleles (14.92 vs. 7.4, respectively), polymorphic information content (0.87 vs. 0.68, respectively), and gene diversity (He; 0.55 vs. 0.38, respectively). Despite the overall differences in the level of diversity, Mantel tests for correlations between eSSR and gSSR pairwise genetic distances were found to be significant for each population as well as for all accessions jointly (RM= 0.54, p = 0.01). Various genetic structure analyses (AMOVA, PCoA, STRUCTURE, unrooted UPGMA tree) revealed a better capacity of eSSRs to distinguish between populations, while gSSRs showed a higher proportion of intrapopulation (among accessions) diversity. We conclude that eSSR and gSSR markers should be employed in conjunction to obtain a high inter- and intra-specific (or inter- and intra-varietal) distinctness.
COSMOLOGICAL MODEL SELECTION
Authors: MUKHERJEE PIA , PARKINSON DAVID
Published: March 2008

We give an overview of the recent progress in the field of cosmological model selection. Model selection statistics, such as those based on information theory and on Bayesian statistics are introduced and discussed. In the Bayesian framework, the marginalised model likelihood, or evidence, is the primary model selection statistic. We describe different methods of computing the evidence, and focus in particular on Nested Sampling. We describe the results of applying model selection methods to new cosmological data such as the CMB measurements by WMAP.
A PERTURBATIVE APPROACH TO A CLASS OF FOKKER–PLANCK EQUATIONS
Authors: HO CHOON-LIN , DAI YAN-MIN
Published: March 2008

In this paper, we present a direct perturbative method to solving certain Fokker–Planck equations, which have constant diffusion coefficients and some small parameters in the drift coefficients. The method makes use of the connection between the Fokker–Planck and Schrödinger equations. Two examples are used to illustrate the method. In the first example, the drift coefficient depends only on time but not on space. In the second example, we consider the Uhlenbeck–Ornstein process with a small drift coefficient. These examples show that such perturbative approach can be a useful tool to obtain approximate solutions of Fokker–Planck equations with constant diffusion coefficients.
KNOWLEDGE BASED ROBOTIC CONTROL AGAINST SATURATION OF ACTUATORS OWING TO FUZZY RULES
Authors: XIAO JIN-ZHUANG , WANG HONG-RUI , WANG HONG-BIN
Published: March 2008

Considering the decreasing performance of robotic systems under the constraints of actuators, this paper concludes the rules of dynamic control process and extracts the knowledge of optimizing the output of robotic controller based on the analysis of a Lyapunov function. Then fuzzy rules are used to express the knowledge and embedded in the controller to direct the dynamic control process. Under this controller, the systemic requirement of high-level outputs of the actuators is limited to a great extent, at the same time the convergent performance is optimized by a fuzzy-sets method from which the saturated fault tolerant control is realized in robotic manipulators. Simulating results on a 2-DOF robot validate the effectiveness of the given controller.
OPTIMAL IMAGE MULTISCALE MOSAIC METHOD BASED ON FUZZY INTEGRAL
Authors: YANG GUOSHENG , ZHANG HUANLONG
Published: March 2008

In order to give attention to the smooth distortion of two image mosaic evaluation indices concurrently, an image multiscale mosaic method based on fuzzy integral is proposed in this paper. Aiming at problems resulting from evaluating mosaic effect of single-factor evaluation index, the integrative evaluation method of the mosaic image based on synthesizing two independent single-factor indices is put forward by using a fuzzy integral which is largely subject to human feeling. According to the optimal image mosaic rules, an optimal weighted function is obtained. With the help of the optimal weighted function, wavelet coefficients are fused at different resolution levels. As a result, a smooth and seamless mosaic image is reconstructed. Finally, experiments are performed on the method presented in this paper.
CONSTRUCTING THE GROUP PRESERVING A SYSTEM OF FORMS
Authors: BROOKSBANK PETER A. , O'BRIEN E. A.
Published: March 2008

We present a practical algorithm to construct the subgroup of the general linear group that preserves a system of bilinear or sesquilinear forms on a vector space defined over a finite field. Components include efficient algorithms to construct the Jacobson radical and the group of units of a matrix algebra.
IRREDUCIBLE DECOMPOSITIONS OF DEGENERACY LOCI OF MATRICES
Authors: ZHAO XU-AN , GAO HONGZHU
Published: March 2008

In this paper, we study the irreducible decompositions of the degeneracy loci of matrices which are defined by rank conditions on upper left submatrices. By introducing the concepts of standard and essential rank functions, we give an explicit classification of these degeneracy loci. Based on standard rank functions, we design an algorithm to write a degeneracy locus as a union of its irreducible components. This gives an answer to a problem raised by Sturmfels.
FACTORIZATIONS OF THE THOMPSON–HIGMAN GROUPS, AND CIRCUIT COMPLEXITY
Authors: BIRGET JEAN-CAMILLE
Published: March 2008

We consider the subgroup lpGk,1of length preserving elements of the Thompson–Higman group Gk,1and we show that all elements of Gk,1have a unique lpGk,1· Fk,1factorization. This applies to the Thompson–Higman group Tk,1as well. We show that lpGk,1is a "diagonal" direct limit of finite symmetric groups, and that lpTk,1is a k∞Prüfer group. We find an infinite generating set of lpGk,1which is related to reversible boolean circuits.

We further investigate connections between the Thompson–Higman groups, circuits, and complexity. We show that elements of Fk,1cannot be one-way functions. We show that describing an element of Gk,1by a generalized bijective circuit is equivalent to describing the element by a word over a certain infinite generating set of Gk,1; word length over these generators is equivalent to generalized bijective circuit size.

We give some coNP-completeness results for Gk,1(e.g., the word problem when elements are given by circuits), and [Formula: see text]-completeness results (e.g., finding the lpGk,1· Fk,1factorization of an element of Gk,1given by a circuit).
PHASE TRANSFORMATION AND R–T CHARACTERISTICS OF VACUUM ANNEALED VANADIUM OXIDE THIN FILMS
Authors: WANG Y. L. , LI M. C. , ZHAO L. C.
Published: March 2008

Polycrystalline vanadium oxide ( VO x) thin films with mixed phases of V 6 O 13 + VO 2 (M) are deposited onto p-doped Si (100) substrates at 430°C using magnetron sputtering. By vacuum annealing on as-deposited VO x thin films at 450°C, at different annealing times we obtained nanoscale polycrystalline VO x thin films with two or more mixed phases. With the annealing time increasing, the phases of the films underwent the following transformation: V 6 O 13 + VO 2 ( M ) → VO 2 ( M ) + VO 2 ( B ) → VO 2 ( B ) + VO 2 ( M ) + V 5 O 9 → V 4 O 7 + V 5 O 9. The surface of VO x thin films prepared in different conditions is of high quality with mean grain size ranging from 80 to 300 nm and the R a being about 20nm. The lowest temperature coefficient of resistance at ambient temperature (20°C) of -2% K-1 is found in the VO x thin film annealed at 450°C for 8 h with mixed phases of VO 2 ( M ) + VO 2 ( B ), which can meet the needs of microbolometer materials.
PHOTOCHROMIC KINETICS OF ASYMMETRICAL DIARYLETHENES IN DIFFERENT SOLVENTS AND IN PMMA FILMS
Authors: LI MIN , PU SHOUZHI , ZHENG CHUNHONG , LUO MINGBIAO , LE ZHANGGAO
Published: March 2008

Three new asymmetric photochromic diarylethenes bearing fluorine atoms at the ortho-, meta-, or para-position of one terminal phenyl group were synthesized, and their photochromism and kinetics of the photochromic cyclization/cycloreversion both in different solvents and in PMMA films were investigated. The results showed that the cyclization/cycloreversion process of these compounds were determined to be zeroth/first order reaction, and the reaction rates (k) were obtained from the slope of every line. The substituent position effect on the cycloreversion process of the three compounds was remarkable and the solvent polarity enhanced this effect. The values of reaction rates in PMMA films were quite different from those in solvents indicating that the kinetics processes of the three compounds taking place in PMMA films differs from the same processes occurring in common solvent.
ELECTROCHEMICAL PERFORMANCE OF MICROBATTERIES USING CRYSTALLIZED LiCoO2 AND NANO-CRYSTALLINE LiMn2O4 FILM AS CATHODES AND AMORPHOUS LiNiVO4 AS ANODE
Authors: TANG S. B. , LAI M. O. , LU L.
Published: March 2008

Three different electrode films of highly crystallized LiCoO 2, nano-crystalline LiMn 2 O 4 as cathode and amorphous LiNiVO 4 as anode were grown on stainless steel substrates by pulsed laser deposition. Microbatteries were assembled using liquid electrode of LiPF 6. The microbatteries were electrochemically tested by charge/discharge cycling and cyclic voltammetry. Both LiCoO 2/ LiPF 6/ LiNiVO 4 and LiMn 2 O 4/ LiPF 6/ LiNiVO 4 cells showed smooth charge/discharge curves. Although the cells faced a fast capacity loss in the first 10 cycles, about 20 μA/cm2 μm of discharge capacity was attainable after 20 cycles.
The Challenges Facing Traditional Chinese Medicine in the West
Authors: Lee Henry
Published: March 2008

This article Argues about the Safety and Quality of the Traditional Chinese Medicinal Facing in the West.
Claudin-3 tight junction proteins inTetraodon nigroviridis: cloning, tissue-specific expression, and a role in hydromineral balance
Authors: Bagherie-Lachidan Mazdak , Wright Stephen I. , Kelly Scott P.
Published: March 2008

Claudins are a large family of integral transmembrane tight junction (TJ) proteins involved in regulating the permeability of the paracellular pathway. In these studies, we clone and describe the tissue distribution of four claudin-3 genes (designated Tncldn3a, Tncldn3b, Tncldn3c, and Tncldn3d) from the euryhaline spotted green puffer fish Tetraodon nigroviridis and examine the response of Tetraodon and Tncldn3 mRNAs to salinity variation (freshwater, FW; seawater, SW; and hypersaline seawater, HSW). In Tetraodon, genes encoding for claudin-3 TJ proteins are widely expressed, suggesting that claudin-3 proteins participate in regulating paracellular permeability across various epithelia within fishes. Of particular note is the widespread distribution of Tncldn3 genes in tissues that regulate hydromineral balance (gills, skin, kidney, and intestine). Renal and intestinal tissues express all four Tncldn3 genes, while the gills and skin specifically express Tncldn3a and Tncldn3c. In response to salinity variation, Tetraodon exhibits characteristics typical of a euryhaline fish species: moderate changes in blood osmolality and muscle moisture content; alterations in gill, kidney, and intestinal Na+-K+-ATPase activity; and unaltered Na+-K+-ATPase activity in the integument. In conjunction with these changes, Tncldn3 mRNA expression exhibits marked and significant salinity-dependent alterations that are both tissue and gene specific. Overall, our data suggest that a decreased abundance of claudin-3 in Tetraodon occurs in “leakier” epithelia and that claudin-3 TJ proteins will likely play an important role in the maintenance of hydromineral balance across osmoregulatory epithelia of euryhaline fishes.
Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca2+release mechanism
Authors: Colleran Patrick N. , Behnke Bradley J. , Wilkerson M. Keith , Donato Anthony J. , Delp Michael D.
Published: March 2008

Previous work has shown that orthostatic hypotension associated with cardiovascular deconditioning results from inadequate peripheral vasoconstriction. We used the hindlimb-unloaded (HU) rat in this study as a model to induce cardiovascular deconditioning. The purpose of this study was to test the hypothesis that 14 days of HU diminishes vasoconstrictor responsiveness of mesenteric resistance arteries. Mesenteric resistance arteries from control ( n = 43) and HU ( n = 44) rats were isolated, cannulated, and pressurized to 108 cm H2O for in vitro experimentation. Myogenic (intralumenal pressure ranging from 30 to 180 cm H2O), KCl (2–100 mM), norepinephrine (NE, 10−9–10−4M) and caffeine (1–20 mM) induced vasoconstriction, as well as the temporal dynamics of vasoconstriction to NE, were determined. The active myogenic and passive pressure responses were unaltered by HU when pressures remained within physiological range. However, vasoconstrictor responses to KCl, NE, and caffeine were diminished by HU, as well as the rate of constriction to NE (C, 14.8 ± 3.6 μm/s vs. HU 7.6 ± 1.8 μm/s). Expression of sarcoplasmic reticulum Ca2+ATPase 2 and ryanodine 3 receptor mRNA was unaffected by HU, while ryanodine 2 receptor mRNA and protein expression were diminished in mesenteric arteries from HU rats. These data suggest that HU-induced and microgravity-associated orthostatic intolerance may be due, in part, to an attenuated vasoconstrictor responsiveness of mesenteric resistance arteries resulting from a diminished ryanodine 2 receptor Ca2+release mechanism.
Slc39a1 to 3 (subfamily II) Zip genes in mice have unique cell-specific functions during adaptation to zinc deficiency
Authors: Kambe Taiho , Geiser Jim , Lahner Brett , Salt David E. , Andrews Glen K.
Published: March 2008

Subfamily II of the solute carrier (Slc)39a family contains three highly conserved members (ZIPs 1–3) that share a 12-amino acid signature sequence present in the putative fourth transmembrane domain and function as zinc transporters in transfected cells. The physiological significance of this genetic redundancy is unknown. Here we report that the complete elimination of all three of these Zip genes, by targeted mutagenesis and crossbreeding mice, causes no overt phenotypic effect. When mice were fed a zinc-adequate diet, several indicators of zinc status were indistinguishable between wild-type and triple-knockout mice, including embryonic morphogenesis and growth, alkaline phosphatase activity in the embryo, ZIP4 protein in the visceral yolk sac, and initial rates (30 min) of accumulation/retention of 67Zn in liver and pancreas. When mice were fed a zinc-deficient diet, embryonic membrane-bound alkaline phosphatase activity was reduced to a much greater extent, and 80% of the embryos of the triple-knockout mice developed abnormally compared with 12% of the embryos of wild-type mice. During zinc deficiency, the accumulation/retention (3 h) of 67Zn in the liver and pancreas of weanlings was significantly impaired in the triple-knockout mice compared with wild-type mice. Thus none of these three mammalian Zip genes apparently plays a critical role in zinc homeostasis when zinc is replete, but they play important, noncompensatory roles when this metal is deficient.
l-arginine-induced glomerular hyperfiltration response: the roles of insulin and ANG II
Authors: Ruiz Mario , Singh Prabhleen , Thomson Scott C. , Munger Karen , Blantz Roland C. , Gabbai Francis B.
Published: March 2008

Infusion of l-arginine produces an increase in glomerular filtration via kidney vasodilation, correlating with increased kidney excretion of nitric oxide (NO) metabolites, but the specific underlying mechanisms are unknown. We utilized clearance and micropuncture techniques to examine the whole kidney glomerular filtration rate (GFR) and single nephron GFR (SNGFR) responses to 1) l-arginine (ARG), 2) ARG+octreotide (OCT) to block insulin release, 3) ARG+OCT+insulin (INS) infusion to duplicate ARG-induced insulin levels, and 4) losartan (LOS), an angiotensin AT-1 receptor blocker, +ARG+OCT. ARG infusion increased GFR, while increasing insulin levels. OCT coinfusion prevented this increase in GFR, but with insulin infusion to duplicate ARG induced rise in insulin, the GFR response was restored. Identical insulin levels in the absence of ARG had no effect on GFR. In contrast to ARG infusion alone, coinfusion of OCT with ARG reduced proximal tubular fractional and absolute reabsorption potentially activating tubuloglomerular feedback. Losartan infusion, in addition to ARG and OCT (LOS+ARG+OCT), restored the increase in both SNGFR and proximal tubular reabsorption, without increasing insulin levels. In conclusion, 1) hyperfiltration responses to ARG require the concurrent, modest, permissive increase in insulin; 2) inhibition of insulin release after ARG reduces proximal reabsorption and prevents the hyperfiltration response; and 3) inhibition of ANG II activity restores the hyperfiltration response, maintains parallel increases in proximal reabsorption, and overrides the arginine/octreotide actions.
Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction
Authors: Kalinowski Leszek , Dobrucki Lawrence W. , Meoli David F. , Dione Donald P. , Sadeghi Mehran M. , Madri Joseph A. , Sinusas Albert J.
Published: March 2008

The αvβ3-integrin is expressed in angiogenic vessels in response to hypoxia and represents a potential novel target for imaging myocardial angiogenesis. This study evaluated the feasibility of noninvasively tracking hypoxia-induced αvβ3-integrin activation within the myocardium as a marker of angiogenesis early after myocardial infarction. Acute myocardial infarction was produced by coronary artery occlusion in rodent and canine studies. A novel 111In-labeled radiotracer targeted at the αvβ3-integrin (111In-RP748) was used to localize regions of hypoxia-induced angiogenesis early after infarction. In rodent studies, the specificity of 111In-RP748 for αvβ3-integrin was confirmed with a negative control compound (111In-RP790), and regional uptake of these compounds correlated with 201Tl perfusion and a 99mTc-labeled nitroimidazole (BRU59-21), which was used as a quantitative marker of myocardial hypoxia. The ex vivo analysis demonstrated that only 111In-RP748 was selectively retained in infarcted regions with reduced 201Tl perfusion and correlated with uptake of BRU59-21. In canine studies, myocardial uptake of 111In-RP748 was assessed using in vivo single-photon-emission computed tomography (SPECT), ex vivo planar imaging, and gamma well counting of myocardial tissue and correlated with 99mTc-labeled 2-methoxy-2-methyl-propyl-isonitrile (99mTc-sestamibi) perfusion. Dual-radiotracer in vivo SPECT imaging of 111In-RP748 and 99mTc-sestamibi provided visualization of 111In-RP748 uptake within the infarct region, which was confirmed by ex vivo planar imaging of excised myocardial slices. Myocardial 111In-RP748 retention was associated with histological evidence of αvβ3-integrin expression/activation in the infarct region. 111In-RP748 imaging provides a novel noninvasive approach for evaluation of hypoxia-induced αvβ3-integrin activation in myocardium early after infarction and may prove useful for directing and evaluating angiogenic therapies in patients with ischemic heart disease.
Getting Information on|Ue3|2from Neutrinoless Double Beta Decay
Authors: Merle Alexander , Rodejohann Werner
Published: March 2008

We consider the possibility to gain information on the lepton mixing matrix element|Ue3|from an improved experimental limit on the effective neutrino mass governing neutrinoless double beta decay. We show that typically a lower limit on|Ue3|as a function of the smallest neutrino mass can be set. Furthermore, we give the values of the sum of neutrino masses and|Ue3|which are allowed and forbidden by an experimental upper limit on the effective mass. Alternative explanations for neutrinoless double beta decay, Dirac neutrinos or unexplained cosmological features would be required if future measurements showed that the values lie in the respective regions. Moreover, we show that a measurement of|Ue3|from neutrinoless double beta decay is very difficult due to the expected errors on the effective mass and the oscillation parameters.
Decreased Expression of UK114 Is Related to the Differentiation Status of Human Hepatocellular Carcinoma
Authors: Chong Chin-Liew , Huang Shiu-Feng , Hu Cheng-po , Chen Ya-Ling , Chou Hsin-Ying , Chau Gar-Yang , Shew Jin-Yuh , Tsai Yue-Lin , Chen Chiung-Tong , Chang Chungming , Chen Mong-Liang
Published: March 2008

Previous studies have identified that the expression of UK114 is tissue specific and the protein has been found to be most abundant in liver and kidney. However, the expression of UK114 in human hepatocellular carcinoma and its relationship to differentiation and transformation of hepatocellular carcinoma have not been studied. In this study, the expression of UK114 in human hepatocellular carcinoma was examined by Northern and Western blot analyses. We found that UK114 was significantly down-regulated in most of hepatocellular carcinoma tissues compared with adjacent nontumor tissues (72.7%) at both mRNA and protein levels. We looked into the possibility that this decreased expression of UK114 in the hepatocellular carcinoma tissues may play a role in the differentiation or tumorigenicity of hepatocellular carcinoma. Immunohistochemical staining showed that the reduced expression of UK114 in hepatocellular carcinoma tissues was correlated with the tumor differentiation status as graded by the Edmondson-Steiner classification. On the other hand, overexpression of UK114 was not able to suppress the proliferation of human hepatoma cells and tumorigenicity in nude mice. These results suggest that UK114 does not seem to act as a tumor suppressor gene; however, it may useful as a biomarker that will assist in the grading of the differentiation status of hepatocellular carcinoma samples. (Cancer Epidemiol Biomarkers Prev 2008;17(3):535–42)
Is Mammography Adequate for Screening Women with Inherited BRCA Mutations and Low Breast Density?
Authors: Bigenwald Rachel Z. , Warner Ellen , Gunasekara Anoma , Hill Kimberley A. , Causer Petrina A. , Messner Sandra J. , Eisen Andrea , Plewes Donald B. , Narod Steven A. , Zhang Liying , Yaffe Martin J.
Published: March 2008

Background: Several observational studies have shown that magnetic resonance imaging (MRI) is significantly more sensitive than mammography for screening women over age 25 at high risk for hereditary breast cancer; however, MRI is more costly and less specific than mammography. We sought to determine the extent to which the low sensitivity of mammography is due to greater breast density.

Methods: Breast density was evaluated for all patients on a high-risk screening study who were diagnosed with breast cancer between November 1997 and July 2006. Density was measured in two ways: qualitatively using the four categories characterized by the Breast Imaging Reporting and Data System and quantitatively using a computer-aided technique and classified as (a) ≤10%, (b) 11% to 25%, (c) 26% to 50%, and (d) >50% density. Comparison of sensitivity of mammography (and MRI) for each individual density category and after combining the highest two and lowest two density categories was done using Fisher's exact test.

Results: A total of 46 breast cancers [15 ductal carcinoma in situ (DCIS) and 31 invasive] were diagnosed in 45 women (42 with BRCA mutations). Mean age was 48.3 (range, 32-68) years. Overall, sensitivity of mammography versus MRI was 20% versus 87% for DCIS and 26% versus 90% for invasive cancer. There was a trend towards greater mammographic sensitivity for invasive cancer in women with fattier breasts compared with those with greater breast density (37-43% versus 8-12%; P = 0.1), but this trend was not seen for DCIS.

Conclusion: It is necessary to add MRI to mammography for screening women with BRCA mutations even if their breast density is low. (Cancer Epidemiol Biomarkers Prev 2008;17(3):706–11)
Comparative Bioavailability of Sulindac in Capsule and Tablet Formulations
Authors: Reid Joel M. , Mandrekar Sumithra J. , Carlson Elsa C. , Harmsen W. Scott , Green Erin M. , McGovern Renee M. , Szabo Eva , Ames Matthew M. , Boring Daniel , Limburg Paul J. ,   for the Cancer Prevention Network
Published: March 2008

The cyclooxygenase (COX)-2 enzyme appears to be an important target for cancer chemoprevention. Given the recent emergence of potentially serious cardiovascular toxicity associated with selective COX-2 inhibitors, nonsteroidal antiinflammatory drugs (NSAIDs), which inhibit both COX-1 and COX-2, have received renewed attention as candidate chemoprevention agents. Sulindac has shown consistent chemopreventive potential in preclinical studies as well as in a limited number of clinical trials reported to date. For the current pharmacokinetic study, sulindac capsules were prepared to facilitate ample agent supplies for future intervention studies. Encapsulation of the parent compound (sulindac sulfoxide) can be readily accomplished, but the effects of alternate formulations on bioavailability have not been rigorously examined. In the present single-dose, two-period crossover trial, we conducted pharmacokinetic analyses of sulindac in capsule (test) versus tablet (reference) formulations. Overall, bioavailability appeared to be higher for the capsule compared with the tablet formulation based on test-to-reference pharmacokinetic variable ratios for the parent compound alone. However, additional analyses based on the sulfide and sulfone metabolites of sulindac with the same pharmacokinetic variables indicated similar chemopreventive exposures between the capsule and tablet formulations. These data support the use of sulindac capsules, which can be readily prepared with matching placebos, in future blinded chemoprevention trials. (Cancer Epidemiol Biomarkers Prev 2008;17(3):674–9)
Fetal MouseCyp1b1and Transplacental Carcinogenesis from Maternal Exposure to Dibenzo(a,l)pyrene
Authors: Castro David J. , Baird William M. , Pereira Clifford B. , Giovanini Jack , Löhr Christiane V. , Fischer Kay A. , Yu Zhen , Gonzalez Frank J. , Krueger Sharon K. , Williams David E.
Published: March 2008

Dibenzo(a,l)pyrene (DBP) is among the most potent carcinogenic polycyclic aromatic hydrocarbons. Previously, we showed that DBP administration to pregnant mice resulted in high mortality of offspring from an aggressive T-cell lymphoma. All mice that survive to 10 months of age exhibit lung tumors with high multiplicity. Recombinant cytochrome P450 (cyp) 1b1 from mice and the homologue 1B1 in humans exhibit high activity toward the metabolic activation of DBP. Targeted disruption of the cyp1b1 gene protects against most DBP-dependent cancers. Mice heterozygous for the disrupted cyp1b1 allele were used to examine the effect of cyp1b1 gene dosage on DBP transplacental carcinogenesis. Dams were treated with 1 or 15 mg/kg of DBP or 50 mg/kg of benzo(a)pyrene. Cyp1b1-null offspring did not develop lymphoma, whereas wild-type and heterozygous siblings, born to dams given the high dose of DBP, exhibited significant mortalities between 10 and 30 weeks of age. At 10 months, all groups had lung adenomas or carcinomas [9.5%, 40.3%, 25.6%, and 100% incidences for controls, benzo(a)pyrene, 1 and 15 mg/kg DBP, respectively]. Cyp1b1 status did not alter benzo(a)pyrene-dependent carcinogenesis. At 1 mg/kg DBP, cyp1b1 status altered the incidence of lung tumors (19.0, 27.8, and 28.6% for nulls, heterozygous, and wild-type, respectively). At 15 mg/kg, tumor multiplicities in cyp1b1 wild-type (9.3) and heterozygous (9.5) offspring were nearly twice that of cyp1b1-null siblings (5.0). These data confirm that cyp1b1 bioactivation of DBP occurs in fetal target tissues, following transplacental exposure, with the thymus and lung as primary and secondary targets, respectively.
Regulation of Prostaglandin Transporters in Colorectal Neoplasia
Authors: Holla Vijaykumar R. , Backlund Michael G. , Yang Peying , Newman Robert A. , DuBois Raymond N.
Published: March 2008

Prostaglandin E2 (PGE2) promotes cancer progression by affecting cell proliferation, apoptosis, angiogenesis, and the immune response. It has been reported that PGE2 is transported or passes through the cell membrane via prostaglandin-specific transporters including the prostaglandin transporter (PGT, an influx transporter) and the multidrug resistance-associated protein 4 (an efflux transporter). PGT can facilitate the removal of PGE2 from the extracellular milieu by transporting it into the cell, where 15-hydroxyprostaglandin dehydrogenase (15-PGDH) then oxidizes PGE2 into 15-keto PGE2. We previously reported that 15-PGDH expression is reduced in most colorectal cancers, indicating the tumor suppressor role of this gene. In the present study, we show that PGT expression is also decreased (whereas multidrug resistance-associated protein 4 expression is elevated) in human colorectal cancer specimens (compared with expression in normal mucosa) and in colorectal cancer cell lines. Furthermore, we found that PGT expression decreased in premalignant adenomas in APCmin mice and was partially restored (in human colorectal cancer cell lines) by treatment with a DNA demethylating agent or histone deacetylase inhibitor. Forced PGT overexpression in vitro dose dependently reduced extracellular PGE2 levels and increased intracellular levels of its catabolic product 15-keto PGE2. Our collective data suggest that the existing model to explain increased PGE2 in colorectal neoplasia should be modified to include the novel mechanism of coordinated up- and down-regulation of genes involved in PGE2 transport.
High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO)
Authors: Torup Lars , Bochsen Louise , Kjalke Marianne , Abel Kristin , Theilgaard-Monch Kim , Johansson Pär , Bjørn Søren , Kirkeby Agnete , Gerwien Jens , Leist Marcel
Published: March 2008

The haematopoietic hormone erythropoietin (EPO) has neuroprotective properties and is currently being explored for treatment of stroke and other neurological disorders. Short-term, high-dose treatment with EPO seems to improve neurological function of stroke patients but may be associated with increased thrombotic risk, whereas alternative non-erythropoietic neuroprotective derivatives of EPO, such as carbamylated EPO (CEPO), may be devoid of such side-effects. We investigated the effects of short-term, high-dose treatment with EPO and CEPO on platelet function and haemostasis in healthy mice and rats. Animals received three daily doses of EPO or CEPO (50 μg/kg), and blood was compared with respect to alterations in haematology and platelet reactivity. In rats, treatment with EPO increased the haematocrit to >50% and the mean platelet volume by 37%,while CEPO had no effect on these parameters. Platelets from EPO-treated rats showed an increased sensitivity to thrombin receptor agonist peptides and elevated plasma levels of soluble P-selectin (sP-selectin) were found in treated mice. Further indicators of platelet hyperreactivity in EPO, but not CEPO-treated animals, were significantly increased aggregatory responses to collagen in whole blood and platelet-rich plasma (PRP).The increased platelet reactivity was paralleled by a decreased bleeding time after tail transection in rats. Samples from EPO-treated rats showed an attenuated response to ADP in whole blood aggregometry and thrombelastography (TEG) platelet mapping but not in apyrase-treated PRP, suggesting involvement of ADP receptor desensitization. These findings suggest that while EPO affects various aspects of platelet function, CEPO is devoid of such effects.
Time course of prothrombotic and proinflammatory substance release after intracoronary stent implantation
Authors: Jordanova Nelli , Strehblow Christoph , Syeda Bonni , Meyer Brigitte , Charvat Silvia , Zorn Gerlinde , Scheinig Daniela , Wojta Johann , Huber Kurt , Glogar Dietmar , Gyöngyösi Mariann , Wexberg Paul
Published: March 2008

We hypothesized that restenosis after coronary stenting is predicted by elevated levels of markers of thrombus formation and inflammation. Plasma levels of representative markers of inflammation, the thrombin and plasmin activation systems and adhesion molecules were measured in 59 patients with stable angina pectoris before, immediately after and 6 hours (h), 12 h, 24 h, one month and six months after elective stent implantation (radioactive phosphorus-32 stents /RSs/ n=16,bare-metal stents /BMSs/ n=43). All patients underwent clinical and angiographic follow-up (FUP) six months after stenting. RSs had significantly higher angiographic severity of restenosis than BMSs (47.1 ± 20.1% vs. 27.6 ± 22.0%, p=0.003). Repeated measures ANOVA revealed significant differences between the BMS and RS groups as regards the increases in plasma levels of vascular cell adhesion molecule-1 (VCAM-1, p=0.022), plasminogen activator inhibitor-1 (PAI-1, p=0.047), tissue-type plasminogen activator (tPA, p=0.047) and CD40 ligand (CD40L, p=0.038). tPA levels tended to increase immediately after stenting in both groups, whereas the PAI-1 level one month after stenting was elevated significantly only in the RS group. In the RS group, the plasma levels of CD40L were increased at 24 h and six months after stenting, and the VCAM-1 level rose immediately after stenting and remained high during the FUP. Multivariate analysis on pooled laboratory data of both groups revealed elevated levels of VCAM-1 at 12 h and at six months as significant predictors of the severity of stent restenosis. In conclusion, the process of inflammation and thrombosis occurring after coronary interventions seems to be prolonged and enhanced in patients with highgrade restenosis at the follow up.
Differential Behaviors of Atrial Versus Ventricular Fibroblasts
Authors: Burstein Brett , Libby Eric , Calderone Angelino , Nattel Stanley
Published: March 2008

Background—

In various heart disease paradigms, atria show stronger fibrotic responses than ventricles. The possibility that atrial and ventricular fibroblasts respond differentially to pathological stimuli has not been examined.

Methods and Results—

We compared various morphological, secretory, and proliferative response indexes of canine atrial versus ventricular fibroblasts. Cultured atrial fibroblasts showed faster cell surface area increases, distinct morphology at confluence, and greater α-smooth muscle actin expression than ventricular fibroblasts. Atrial fibroblast proliferation ([
3
H]thymidine incorporation) responses were consistently greater for a range of growth factors, including fetal bovine serum, platelet-derived growth factor (PDGF), basic fibroblast growth factor, angiotensin II, endothelin-1, and transforming growth factor-β
1
. Normal atrial tissue showed larger myofibroblast density compared with ventricular tissue, and the difference was exaggerated by congestive heart failure. Congestive heart failure atria showed larger fractions of fibroblasts in mitotic phases compared with ventricles and displayed enhanced gene expression of fibroblast-selective markers (collagen-1, collagen-3, fibronectin-1). Gene microarrays revealed 225 differentially expressed transcript probe sets between paired atrial and ventricular fibroblast samples, including extracellular matrix (eg, fibronectin, laminin, fibulin), cell signaling (PDGF, PDGF receptor, angiopoietin, vascular endothelial growth factor), structure (keratin), and metabolism (xanthine dehydrogenase) genes, identifying PDGF as a candidate contributor to atrial-ventricular fibroblast differences. PDGF receptor gene expression was greater in normal atrium compared with ventricle, and congestive heart failure differentially enhanced atrial versus ventricular PDGF and PDGF receptor gene expression. PDGF receptor protein expression and α-smooth muscle actin protein expression were enhanced in isolated congestive heart failure fibroblasts. The PDGF receptor tyrosine kinase inhibitor AG1295 eliminated fetal bovine serum– and transforming growth factor-β
1
–stimulated atrial-ventricular fibroblast proliferative response differences.

Conclusions—

Atrial fibroblasts behave differently than ventricular fibroblasts over a range of in vitro and in vivo paradigms, with atrial fibroblasts showing enhanced reactivity that may explain greater atrial fibrotic responses. PDGF signaling is particularly important for atrium-selective fibroblast responses and may represent a novel target for arrhythmogenic atrial structural remodeling prevention.
Screening, Treatment, and Control of Hypertension in US Private Physician Offices, 2003–2004
Authors: Ma Jun , Stafford Randall S.
Published: March 2008

Essential hypertension is the most common diagnosis in US primary care settings for middle-aged persons and seniors. Yet, data on hypertension screening, treatment, and control in such settings are limited. We analyzed National Ambulatory Medical Care Survey data to examine the rates of and factors associated with hypertension screening, treatment, and control during US office visits in 2003 and 2004. Blood pressure was measured in 56% (95% confidence limits: 52% to 59%) of all visits by patients ≥18 years of age and in 93% (95% confidence limits: 89% to 96%) of hypertensive patient visits. Among the latter, 62% (95% confidence limits: 55% to 69%) were treated. Diuretics were the most commonly prescribed antihypertensive agents (46%; 95% confidence limits: 41% to 50%), and combination therapy was reported in 58% (95% confidence limits: 54% to 63%) of treated visits. Only 39% (95% confidence limits: 34% to 43%) of treated visits were at recommended blood pressure goals. The odds of not being screened for hypertension were notably greater for visits with a provider other than a primary care physician or cardiologist (10.0; 95% confidence limits: 5.5 to 16.7) and for nonwell care visits (5.6; 95% confidence limits: 3.6 to 8.3). Greater odds of not being treated for hypertension were noted by geographic region (South versus Northeast: 2.6; 95% confidence limits: 1.2 to 5.6) and visit type (first time versus return visits; 1.6; 95% confidence limits: 1.1 to 2.4). The odds of not having blood pressure controlled were greater for patients with comorbidities (1.6; 95% confidence limits: 1.1 to 2.4). In conclusion, more intervention efforts are needed to further reduce the gaps and variations in routine practice in relation to evidence-based practice guidelines for hypertension screening, treatment, and control.
Democratization and the Varieties of International Organizations
Authors: Mansfield Edward D. , Pevehouse Jon C.
Published: March 2008

Scholars of international relations have devoted remarkably little attention to the issue of why and when states enter international organizations (IOs). We argue that states have particular reason to enter IOs during the process of democratization. In the midst of a democratic transition, state leaders have difficulty making a credible commitment to sustain reforms, since they can benefit from rolling back liberalization. Gaining membership in an IO can enhance the credibility of leaders' commitments to democratic reforms. However, not all IOs are equally useful in this regard. We distinguish between IOs that cover standards in areas such as human rights and environmental protection, those that regulate economic activity, and those that are forums for addressing broad political problems. We argue that democratizing states have greater reason to join standards-based and economic IOs than political organizations. The results of a set of statistical tests support this argument.