bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Endogenous B-Type Natriuretic Peptide at Very Low Concentrations in Patients With Heart Failure
Authors: Niederkofler Eric E. , Kiernan Urban A. , O'Rear Jessica , Menon Santosh , Saghir Syed , Protter Andrew A. , Nelson Randall W. , Schellenberger Ute
Published: October 2008

Background—

The myocardium secretes B-type natriuretic peptide (BNP) in response to stimuli associated with heart failure (HF). However, high immunoreactive-BNP levels in patients with HF are associated with a paradoxical lack of natriuretic response. We hypothesized that commercially available assays for immunoreactive BNP do not reflect the bioactivity of the natriuretic peptide system, because they measure both unprocessed inactive pro-BNP and mature BNP 1-32. We describe an assay for the detection of bioactive BNP 1-32 and confirm very low concentrations in plasma from HF patients.

Methods and Results—

We developed a quantitative mass spectrometry immunoassay to capture endogenous BNP peptides using high affinity antibodies. Bound BNP and its truncated fragments were detected by matrix assisted laser desorption ionization–time of flight mass spectrometry based on their predicted masses. Mass spectrometry immunoassay revealed rapid in vitro degradation of BNP 1-32 in plasma, which requires plasma collection in the presence of high protease inhibitor concentrations. In 11 of 12 HF patients BNP 1-32 was detectable, ranging from 25 to 43 pg/mL. Several degraded forms of BNP were also detected at similarly low levels. In contrast, parallel measurements of immunoreactive BNP using the Biosite assay ranged from 900 to 5000 pg/mL.

Conclusions—

Detection of endogenous BNP 1-32 requires special preservation of plasma samples. Mass spectrometry immunoassay technology demonstrates that HF patients have low levels of BNP 1-32. Commercially available immunoreactive-BNP assays overrepresent biological activity of the natriuretic peptide system because they cannot distinguish between active and inactive forms. This observation may, in part, explain the “natriuretic paradox.”
The Syntax and Semantics of Prepositions in the Task of Automatic Interpretation of Nominal Phrases and Compounds: A Cross-Linguistic Study
Authors: Girju Roxana
Published: October 2008

In this article we explore the syntactic and semantic properties of prepositions in the context of the semantic interpretation of nominal phrases and compounds. We investigate the problem based on cross-linguistic evidence from a set of six languages: English, Spanish, Italian, French, Portuguese, and Romanian. The focus on English and Romance languages is well motivated. Most of the time, English nominal phrases and compounds translate into constructions of the form N P N in Romance languages, where the P (preposition) may vary in ways that correlate with the semantics. Thus, we present empirical observations on the distribution of nominal phrases and compounds and the distribution of their meanings on two different corpora, based on two state-of-the-art classification tag sets: Lauer's set of eight prepositions and our list of 22 semantic relations. A mapping between the two tag sets is also provided. Furthermore, given a training set of English nominal phrases and compounds along with their translations in the five Romance languages, our algorithm automatically learns classification rules and applies them to unseen test instances for semantic interpretation. Experimental results are compared against two state-of-the-art models reported in the literature.
Muslim Families Comprising Pakistani Fathers and Japanese Mothers: Focusing on the Educational Problems of their Children
Authors: Takeshita Shuko
Published: October 2008

Recently, the educational problems of children with non-Japanese Muslim fathers and Japanese mothers have come to light in Japan. There has been an increase in the number of transnational families in which the Japanese mother and children have moved to an Islamic country for the Islamic education of the children while the non-Japanese father remains in Japan to work. In this paper, I conduct a case study analysis of families comprising Pakistani husbands and Japanese wives, who selected Sharjah in the United Arab Emirates (UAE) as the new place of residence for the wife and children, in view of the difficulties in transmitting Islamic values to the children while living in Japan. In this paper, I focus on the educational problems among Muslim children, and attempt to clarify the types of educational strategy that have been developed using social capital arising from social networks. They have selected an educational strategy with a view toward a transnational social space.
Using a Low-Order Model to Detect and Characterize Tornadoes in Multiple-Doppler Radar Data
Authors: Potvin Corey K. , Shapiro Alan , Yu Tian-You , Gao Jidong , Xue Ming
Published: October 2008

A new multiple-Doppler radar analysis technique is presented for the objective detection and characterization of tornado-like vortices. The technique consists of fitting radial wind data from two or more radars to a simple analytical model of a vortex and its near-environment. The model combines a uniform flow, linear shear flow, linear divergence flow (all of which compose a broadscale flow), and a modified combined Rankine vortex (representing the tornado). The vortex and its environment are allowed to translate. The parameters in the low-order model are determined by minimizing a cost function that accounts for the discrepancy between the model and observed radial winds. Since vortex translation is taken into account, the cost function can be evaluated over time as well as space, and thus the observations can be used at the actual times and locations where they were acquired. The technique is first tested using analytically simulated observations whose wind field and error characteristics are systematically varied. An Advanced Regional Prediction System (ARPS) high-resolution numerical simulation of a supercell and associated tornado is then used to emulate an observation dataset. The method is tested with two virtual radars for several radar-sampling strategies. Finally, the technique is applied to a dataset of real dual-Doppler observations of a tornado that struck central Oklahoma on 8 May 2003. The method shows skill in retrieving the tornado path and radar-grid-scale features of the horizontal wind field in the vicinity of the tornado. The best results are obtained using a two-step procedure in which the broadscale flow is retrieved first.
Advances and Challenges at the National Hurricane Center
Authors: Rappaport Edward N. , Franklin James L. , Avila Lixion A. , Baig Stephen R. , Beven John L. , Blake Eric S. , Burr Christopher A. , Jiing Jiann-Gwo , Juckins Christopher A. , Knabb Richard D. , Landsea Christopher W. , Mainelli Michelle , Mayfield Max , McAdie Colin J. , Pasch Richard J. , Sisko Christopher , Stewart Stacy R. , Tribble Ahsha N.
Published: October 2008

The National Hurricane Center issues analyses, forecasts, and warnings over large parts of the North Atlantic and Pacific Oceans, and in support of many nearby countries. Advances in observational capabilities, operational numerical weather prediction, and forecaster tools and support systems over the past 15–20 yr have enabled the center to make more accurate forecasts, extend forecast lead times, and provide new products and services. Important limitations, however, persist. This paper discusses the current workings and state of the nation’s hurricane warning program, and highlights recent improvements and the enabling science and technology. It concludes with a look ahead at opportunities to address challenges.
No Margin for Error: Educational and Occupational Achievement among Disadvantaged Children of Immigrants
Authors: Portes Alejandro , Fernández-Kelly Patricia
Published: October 2008

The authors review the literature on segmented assimilation and alternative theoretical models on the adaptation of the second generation, summarize the theoretical framework developed in the course of the Children of Immigrants Longitudinal Study, and present evidence from its third survey in South Florida bearing on alternative hypotheses. The majority of second-generation youth are progressing educationally and occupationally, but a significant minority is left behind. The latter group is not distributed randomly across nationalities but corresponds closely to predictions based on immigrant parents' human capital, family type, and modes of incorporation. Members of the second generation, whether successful or unsuccessful, learn English and American culture, but it makes a big difference whether they assimilate by joining the middle class or the marginalized, and largely racialized, population at the bottom of the society. Ethnographic narratives put into perspective quantitative results and highlight the realities of segmented assimilation in current U.S. society.
Ethnic Communities and School Performance among the New Second Generation in the United States: Testing the Theory of Segmented Assimilation
Authors: Kroneberg Clemens
Published: October 2008

This article examines the theory of segmented assimilation, which traces the divergent adaptation of immigrant children in the post-1969 wave to the nature of reception by U.S. society, access to social capital through ethnic communities, and exposure to oppositional cultures of marginalized domestic minorities. The article provides a test of those arguments in the area of school performance. Based on data from the Children of Immigrants Longitudinal Study, indicators of community-based social capital are shown to account for considerable interethnic differences in school performance. The results challenge notions that ethnic communities are generally supportive of the second generation's school performance, while contact with oppositional cultures of domestic minorities is the main cause of lower than average achievement. They support a conditional view of ethnic communities: the extent to which immigrant families' insertion into ethnic communities can support the school performance of their children depends on the communities' socioeconomic profile and level of aspirations.
Deaf and hearing students' referential strategies in writing: What referential cohesion tells us about deaf students' literacy development
Authors: Arfé Barbara , Perondi Irene
Published: October 2008

The ability to organize the referential content of narrative has usually been investigated as a mark of the development of discourse skills. In this study, the pragmatic use of pronominal and nominal forms of reference in written stories was considered instead as a mark of literacy development in deaf and hearing students. Participants in the study were 17 deaf high-school students, 17 school-age matched hearing controls, and 16 hearing second-graders (novice writers) who were asked to write a picture-story, Frog, Where are you?, for a hearing reader who was unacquainted with it. Results revealed that deaf students appear to use the same variety of referential devices as hearing students when writing and, in most cases, these devices are used appropriately. However, the referential strategies of the deaf students were more nominal and less anaphoric than those of their hearing peers. It is concluded that the referential strategies of deaf writers are only superficially similar to those of hearing novice writers, suggesting that deaf students' referential strategies in writing are not merely the product of a delay in development of discourse skills.
Application of magnetic separation technology for the recovery of colemanite from plant tailings
Authors: Alp Ibrahim
Published: October 2008

In this study, colemanite was recovered from tailings produced by the Kestelek (Turkey) Processing Plant by magnetic separation. Magnetic susceptibility measurements revealed that colemanite is diamagnetic in character whereas gangue minerals are weakly paramagnetic, apparently due to the presence of the iron-bearing silicates such as smectite and, to a less extent, illite. Three-stage magnetic separation tests were performed on the size fractions coarser than 75 µm produced from the tailings (31.52% B2O3) using a high-intensity permanent magnetic separator. Under the test conditions a colemanite concentrate with a B2O3 content of 43.74% at 95.06% recovery was shown to be produced from the tailings. The mineralogical composition of the tailings appears to allow the removal of gangue minerals by magnetic separation and hence the production of a concentrate of commercial grade.
Report: New guidelines for characterization of municipal solid waste: the Portuguese case
Authors: da Graça Madeira Martinho Maria , Silveira Ana Isabel , Fernandes Duarte Branco Elsa Maria
Published: October 2008

This report proposes a new set of guidelines for the characterization of municipal solid waste. It is based on an analysis of reference methodologies, used internationally, and a case study of Valorsul (a company that handles recovery and treatment of solid waste in the North Lisbon Metropolitan Area). In particular, the suggested guidelines present a new definition of the waste to be analysed, change the sampling unit and establish statistical standards for the results obtained. In these new guidelines, the sampling level is the waste collection vehicle and contamination and moisture are taken into consideration. Finally, focus is on the quality of the resulting data, which is essential for comparability of data between countries. These new guidelines may also be applicable outside Portugal because the methodology includes, besides municipal mixed waste, separately collected fractions of municipal waste. They are a response to the need for information concerning Portugal (e.g. Eurostat or OECD inquiries) and follow European Union municipal solid waste management policies (e.g. packaging waste recovery and recycling targets and the reduction of biodegradable waste going to landfill).
Progressive Encephalopathy in a Child with Cerebral Folate Deficiency Syndrome
Authors: Bonkowsky Joshua L. , Ramaekers Vincent T. , Quadros Edward V. , Lloyd Michael
Published: October 2008

Cerebral folate deficiency syndrome, a recently recognized cause of developmental delay, regression, and seizures, is associated with autoantibodies against folate receptors. A female child with developmental delay and a history of seizures who presented with seizures and unexplained coma is reported. Extensive testing to evaluate the patient's coma and subsequent developmental regression were unrevealing until the results of her cerebrospinal fluid neurotransmitter analysis returned. These showed low levels of methyltetrahydrofolate, the active metabolite of folate in the cerebrospinal fluid; subsequently, elevated titers of autoantibodies against folate receptors were found. Despite treatment with folinic acid, she developed intractable epilepsy and severe developmental delay.
Clusters and Economic Development Outcomes
Authors: Feser Edward , Renski Henry , Goldstein Harvey
Published: October 2008

Much of the existing empirical research on industry clusters focuses on the detection of clusters for economic development purposes. There are comparatively few studies that relate identified clusters to business and industry growth or that trace changes in designated clusters over time. This article seeks to better understand the link between industry clustering and regional economic outcomes. In a comprehensive study sponsored by the Appalachian Regional Commission and released in 2002, the authors identified technology-based clusters within and on the border of the Appalachian region. The Appalachian technology clusters constituted subregional concentrations of related industrial, research and development, and university-based strengths as of the middle to late 1990s. In this article, the authors investigate how the industries in the identified clusters fared over the subsequent several years in terms of employment and new business formation. They find evidence that clustering is associated with new business formation for selected technology industries but not with employment growth.
Customizing Clusters
Authors: Manning Stephan
Published: October 2008

Western multinational corporations (MNCs) increasingly locate advanced functions, including product development and engineering, in emerging economies to gain access to lower-cost science and engineering (S&E) talent and specialized service providers. Over time, new S&E clusters have developed in emerging economies that are strongly oriented toward global MNC demands. This study investigates the role of foreign MNCs in the formation of these S&E clusters. It is proposed that pioneer MNCs promote the initial development of S&E clusters by customizing local institutions and business practices in accordance with their sourcing needs and based on their experience in other local business contexts, including their home country. As a result, these clusters may develop specialized resources and service capabilities that particularly attract follower MNCs of the same national origin that have similar sourcing needs. This study may inform both cluster formation research and policy making in emerging economies.
Does Music Instruction Help Children Learn to Read? Evidence of a Meta-Analysis
Authors: Standley Jayne M.
Published: October 2008

This meta-analysis of 30 studies using a variety of music interventions to affect reading skills resulted in a moderately strong, significant, overall effect size of d = .32. When music activities incorporate specific reading skills matched to the needs of identified children ( d = .44) or contingent music is used to reinforce reading behavior ( d = .66), benefits are large. The music activities that pair alphabet recognition with phonetic patterns, incorporate word segmentation and sound blending skills, and promote rapid decoding skills are effective in enhancing reading instruction and require little transfer to the assessment methodology. Benefits are greater when the special music reading activities are added to an existing music education curriculum than when replacing it. All schedules of intervention are equally effective regardless of whether daily, intense, short-term, or weekly periodic intervention spread across the school year.
An Exploratory Study of Time Use in the Practice of Music Majors
Authors: Byo James L. , Cassidy Jane W.
Published: October 2008

The purpose of this study is to obtain survey and observation data concerning music education majors' practice room behavior. A survey provided opportunity for participants ( n = 38) to articulate techniques they used in practice. An observation component ( n = 9) provided a view of the use of these techniques in actual practice. All participants articulated common practice techniques but a minority of those in observation analysis consistently used these techniques in optimal ways, thus demonstrating a gap between “knowing” and “intelligent doing.” Overwhelmingly, participants identified better self-discipline as the one thing that would improve practice efficiency. Suggestions for resolving this problem are provided.
Do Music Education Majors Intend to Teach Music? An Exploratory Survey
Authors: Hellman Daniel
Published: October 2008

Preservice music teachers ( N = 152) at six institutions were surveyed on their intent to enter and remain in K–12 music teaching. Respondents provided favorable speculations for entering and remaining in K–12 music teaching. Prevalent responses for desiring a music teaching position were categorized as follows: love for music, sharing music, inspiring and making a difference in students' lives, and having an enjoyable job. Categories for not wanting to obtain a school music teaching position included preferring to work in another area of music, insecurity about teaching skills, and anticipated low pay and job instability. Results are discussed in terms of diversity, teacher attrition, teacher socialization, and teacher identity.
A conifer genomics resource of 200,000 spruce (Picea spp.) ESTs and 6,464 high-quality, sequence-finished full-length cDNAs for Sitka spruce (Picea sitchensis)
Authors: Ralph Steven G , Chun Hye Jung E , Kolosova Natalia , Cooper Dawn , Oddy Claire , Ritland Carol E , Kirkpatrick Robert , Moore Richard , Barber Sarah , Holt Robert A , Jones Steven JM , Marra Marco A , Douglas Carl J , Ritland Kermit , Bohlmann Jörg
Published: October 2008

Background

Members of the pine family (Pinaceae), especially species of spruce (Picea spp.) and pine (Pinus spp.), dominate many of the world's temperate and boreal forests. These conifer forests are of critical importance for global ecosystem stability and biodiversity. They also provide the majority of the world's wood and fiber supply and serve as a renewable resource for other industrial biomaterials. In contrast to angiosperms, functional and comparative genomics research on conifers, or other gymnosperms, is limited by the lack of a relevant reference genome sequence. Sequence-finished full-length (FL)cDNAs and large collections of expressed sequence tags (ESTs) are essential for gene discovery, functional genomics, and for future efforts of conifer genome annotation.

Results

As part of a conifer genomics program to characterize defense against insects and adaptation to local environments, and to discover genes for the production of biomaterials, we developed 20 standard, normalized or full-length enriched cDNA libraries from Sitka spruce (P. sitchensis), white spruce (P. glauca), and interior spruce (P. glauca-engelmannii complex). We sequenced and analyzed 206,875 3'- or 5'-end ESTs from these libraries, and developed a resource of 6,464 high-quality sequence-finished FLcDNAs from Sitka spruce. Clustering and assembly of 147,146 3'-end ESTs resulted in 19,941 contigs and 26,804 singletons, representing 46,745 putative unique transcripts (PUTs). The 6,464 FLcDNAs were all obtained from a single Sitka spruce genotype and represent 5,718 PUTs.

Conclusion

This paper provides detailed annotation and quality assessment of a large EST and FLcDNA resource for spruce. The 6,464 Sitka spruce FLcDNAs represent the third largest sequence-verified FLcDNA resource for any plant species, behind only rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana), and the only substantial FLcDNA resource for a gymnosperm. Our emphasis on capturing FLcDNAs and ESTs from cDNA libraries representing herbivore-, wound- or elicitor-treated induced spruce tissues, along with incorporating normalization to capture rare transcripts, resulted in a rich resource for functional genomics and proteomics studies. Sequence comparisons against five plant genomes and the non-redundant GenBank protein database revealed that a substantial number of spruce transcripts have no obvious similarity to known angiosperm gene sequences. Opportunities for future applications of the sequence and clone resources for comparative and functional genomics are discussed.
Identification of drought-responsive genes in roots of upland rice (Oryza sativa L)
Authors: Rabello Aline R , Guimarães Cléber M , Rangel Paulo HN , da Silva Felipe R , Seixas Daniela , de Souza Emanuel , Brasileiro Ana CM , Spehar Carlos R , Ferreira Márcio E , Mehta Ângela
Published: October 2008

Background

Rice (Oryza sativa L.) germplasm represents an extraordinary source of genes that control traits of agronomic importance such as drought tolerance. This diversity is the basis for the development of new cultivars better adapted to water restriction conditions, in particular for upland rice, which is grown under rainfall. The analyses of subtractive cDNA libraries and differential protein expression of drought tolerant and susceptible genotypes can contribute to the understanding of the genetic control of water use efficiency in rice.

Results

Two subtractive libraries were constructed using cDNA of drought susceptible and tolerant genotypes submitted to stress against cDNA of well-watered plants. In silico analysis revealed 463 reads, which were grouped into 282 clusters. Several genes expressed exclusively in the tolerant or susceptible genotypes were identified. Additionally, proteome analysis of roots from stressed plants was performed and 22 proteins putatively associated to drought tolerance were identified by mass spectrometry.

Conclusion

Several genes and proteins involved in drought-response, as well as genes with no described homologs were identified. Genes exclusively expressed in the tolerant genotype were, in general, related to maintenance of turgor and cell integrity. In contrast, in the susceptible genotype, expression of genes involved in protection against cell damage was not detected. Several protein families identified in the proteomic analysis were not detected in the cDNA analysis. There is an indication that the mechanisms of susceptibility to drought in upland rice are similar to those of lowland varieties.
Acid stress damage of DNA is prevented by Dps binding in Escherichia coliO157:H7
Authors: Jeong Kwang Cheol , Hung Kai Foong , Baumler David J , Byrd Jeffrey J , Kaspar Charles W
Published: October 2008

Background

Acid tolerance in Escherichia coli O157:H7 contributes to persistence in its bovine host and is thought to promote passage through the gastric barrier of humans. Dps (DNA-binding protein in starved cells) mutants of E. coli have reduced acid tolerance when compared to the parent strain although the role of Dps in acid tolerance is unclear. This study investigated the mechanism by which Dps contributes to acid tolerance in E. coli O157:H7.

Results

The results from this study showed that acid stress lead to damage of chromosomal DNA, which was accentuated in dps and recA mutants. The use of Bal31, which cleaves DNA at nicks and single-stranded regions, to analyze chromosomal DNA extracted from cells challenged at pH 2.0 provided in vivo evidence of acid damage to DNA. The DNA damage in a recA mutant further corroborated the hypothesis that acid stress leads to DNA strand breaks. Under in vitro assay conditions, Dps was shown to bind plasmid DNA directly and protect it from acid-induced strand breaks. Furthermore, the extraction of DNA from Dps-DNA complexes required a denaturing agent at low pH (2.2 and 3.6) but not at higher pH (>pH4.6). Low pH also restored the DNA-binding activity of heat-denatured Dps. Circular dichroism spectra revealed that at pH 3.6 and pH 2.2 Dps maintains or forms α-helices that are important for Dps-DNA complex formation.

Conclusion

Results from the present work showed that acid stress results in DNA damage that is more pronounced in dps and recA mutants. The contribution of RecA to acid tolerance indicated that DNA repair was important even when Dps was present. Dps protected DNA from acid damage by binding to DNA. Low pH appeared to strengthen the Dps-DNA association and the secondary structure of Dps retained or formed α-helices at low pH. Further investigation into the precise interplay between DNA protection and damage repair pathways during acid stress are underway to gain additional insight.
Identification of biomarkers in ductal carcinoma in situ of the breast with microinvasion
Authors: Okumura Yasuhiro , Yamamoto Yutaka , Zhang Zhenhuan , Toyama Tatsuya , Kawasoe Teru , Ibusuki Mutsuko , Honda Yumi , Iyama Ken-ichi , Yamashita Hiroko , Iwase Hirotaka
Published: October 2008

Background

Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma in situ (DCIS). DCIS of the breast with an area of focal invasion 1 mm or less in diameter is defined as DCIS with microinvasion, DCIS-Mi. Identification of biological differences between DCIS and DCIS-Mi may aid in understanding of the nature and causes of the progression of DCIS to invasiveness.

Methods

In this study, using resected breast cancer tissues, we compared pure DCIS (52 cases) and DCIS-Mi (28 cases) with regard to pathological findings of intraductal lesions, biological factors, apoptosis-related protein expression, and proliferative capacity through the use of immunohistochemistry and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method.

Results

There were no differences in biological factors between DCIS and DCIS-Mi, with respect to levels of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The frequency of necrosis and positive expression ratio of survivin and Bax were significantly higher in DCIS-Mi than in DCIS. In addition, apoptotic index, Ki-67 index, and positive Bcl-2 immunolabeling tended to be higher in DCIS-Mi than in DCIS. Multivariate analysis revealed that the presence of necrosis and positive survivin expression were independent factors associated with invasion.

Conclusion

Compared with DCIS, DCIS-Mi is characterized by a slightly elevated cell proliferation capacity and enhanced apoptosis within the intraductal lesion, both of which are thought to promote the formation of cell necrotic foci. Furthermore, the differential expression of survivin may serve in deciding the response to therapy and may have some prognostic significance.
Relative persistence of AAV serotype 1 vector genomes in dystrophic muscle
Authors: Pacak Christina A , Conlon Thomas , Mah Cathryn S , Byrne Barry J
Published: October 2008

The purpose of this study was to assess the behavior of pseudotyped recombinant adeno-associated virus type 1 (rAAV2/1) vector genomes in dystrophic skeletal muscle. A comparison was made between a therapeutic vector and a reporter vector by injecting the hindlimb in a mouse model of Limb Girdle Muscular Dystrophy Type 2D (LGMD-2D) prior to disease onset. We hypothesized that the therapeutic vector would establish long-term persistence through prevention of myofiber turnover. In contrast, the reporter vector genome copy number would diminish over time due to disease-associated muscle degradation.

One day old alpha sarcoglycan knockout mice (sgca
-/-) were injected with 1 × 1011 vector genomes of rAAV2/1-tMCK-sgca in one hindlimb and the same dose of rAAV2/1-tMCK-LacZ in the contra lateral hindlimb. Newborn mice are tolerant of the foreign transgene allowing for long-term expression of both the marker and the therapeutic gene in the null background. At 2 time-points following vector administration, hindlimb muscles were harvested and analyzed for LacZ or sarcoglycan expression. Our data demonstrate prolonged vector genome persistence in skeletal muscle from the hindlimbs injected with the therapeutic transgene as compared to hindlimbs injected with the reporter gene. We observed loss of vector genomes in skeletal muscles that were there were not protected by the benefits of therapeutic gene transfer. In comparison, the therapeutic vector expressing sarcoglycan led to reduction or elimination of myofiber loss. Mitigating the membrane instability inherent in dystrophic muscle was able to prolong the life of individual myofibers.
Physical and in silico approaches identify DNA-PK in a Tax DNA-damage response interactome
Authors: Ramadan Emad , Ward Michael , Guo Xin , Durkin Sarah S , Sawyer Adam , Vilela Marcelo , Osgood Christopher , Pothen Alex , Semmes Oliver J
Published: October 2008

Background

We have initiated an effort to exhaustively map interactions between HTLV-1 Tax and host cellular proteins. The resulting Tax interactome will have significant utility toward defining new and understanding known activities of this important viral protein. In addition, the completion of a full Tax interactome will also help shed light upon the functional consequences of these myriad Tax activities. The physical mapping process involved the affinity isolation of Tax complexes followed by sequence identification using tandem mass spectrometry. To date we have mapped 250 cellular components within this interactome. Here we present our approach to prioritizing these interactions via an in silico culling process.

Results

We first constructed an in silico Tax interactome comprised of 46 literature-confirmed protein-protein interactions. This number was then reduced to four Tax-interactions suspected to play a role in DNA damage response (Rad51, TOP1, Chk2, 53BP1). The first-neighbor and second-neighbor interactions of these four proteins were assembled from available human protein interaction databases. Through an analysis of betweenness and closeness centrality measures, and numbers of interactions, we ranked proteins in the first neighborhood. When this rank list was compared to the list of physical Tax-binding proteins, DNA-PK was the highest ranked protein common to both lists. An overlapping clustering of the Tax-specific second-neighborhood protein network showed DNA-PK to be one of three bridge proteins that link multiple clusters in the DNA damage response network.

Conclusion

The interaction of Tax with DNA-PK represents an important biological paradigm as suggested via consensus findings in vivo and in silico. We present this methodology as an approach to discovery and as a means of validating components of a consensus Tax interactome.
Vectors for multi-color bimolecular fluorescence complementation to investigate protein-protein interactions in living plant cells
Authors: Lee Lan-Ying , Fang Mei-Jane , Kuang Lin-Yun , Gelvin Stanton B
Published: October 2008

Background

The investigation of protein-protein interactions is important for characterizing protein function. Bimolecular fluorescence complementation (BiFC) has recently gained interest as a relatively easy and inexpensive method to visualize protein-protein interactions in living cells. BiFC uses "split YFP" tags on proteins to detect interactions: If the tagged proteins interact, they may bring the two split fluorophore components together such that they can fold and reconstitute fluorescence. The sites of interaction can be monitored using epifluorescence or confocal microscopy. However, "conventional" BiFC can investigate interactions only between two proteins at a time. There are instances when one may wish to offer a particular "bait" protein to several "prey" proteins simultaneously. Preferential interaction of the bait protein with one of the prey proteins, or different sites of interaction between the bait protein and multiple prey proteins, may thus be observed.

Results

We have constructed a series of gene expression vectors, based upon the pSAT series of vectors, to facilitate the practice of multi-color BiFC. The bait protein is tagged with the C-terminal portion of CFP (cCFP), and prey proteins are tagged with the N-terminal portions of either Venus (nVenus) or Cerulean (nCerulean). Interaction of cCFP-tagged proteins with nVenus-tagged proteins generates yellow fluorescence, whereas interaction of cCFP-tagged proteins with nCerulean-tagged proteins generates blue fluorescence. Additional expression of mCherry indicates transfected cells and sub-cellular structures. Using this system, we have determined in both tobacco BY-2 protoplasts and in onion epidermal cells that Agrobacterium VirE2 protein interacts with the Arabidopsis nuclear transport adapter protein importin α-1 in the cytoplasm, whereas interaction of VirE2 with a different importin α isoform, importin α-4, occurs predominantly in the nucleus.

Conclusion

Multi-color BiFC is a useful technique to determine interactions simultaneously between a given" bait" protein and multiple "prey" proteins in living plant cells. The vectors we have constructed and tested will facilitate the study of protein-protein interactions in many different plant systems.
Prognostic implication of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma: a tissue microarray study
Authors: Liu Zheng , Fu Qiang , Lv Jiaju , Wang Facheng , Ding Kejia
Published: October 2008

Background

p27Kip1 plays a major role as a negative regulator of the cell cycle. The regulation of p27Kip1 degradation is mediated by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. However, little is known regarding the prognostic utility of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma.

Methods

Immunohistochemistry was performed for p27Kip1, Skp2 and Cks1 in tissue microarrays of 482 renal cell carcinomas with follow-up. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance.

Results

Immunoreactivity of p27Kip1, Skp2 and Cks1 was noted in 357, 71 and 82 patients, respectively. Skp2 and Cks1 expression were not noted in chromophobe cancers. A strong correlation was found between Skp2 and Cks1 expression (P < 0.001), both of which were inversely related to p27Kip1 levels (P = 0.006 and P < 0.001), especially in primary and clear-cell cancers. Low p27Kip1 expression and Skp2 expression were correlated with larger tumor size and higher stage, as well as tumor necrosis. Cks1 expression was only correlated with tumor size. In univariate analysis, low p27Kip1 expression, Skp2 and Cks1 expression were all associated with a poor prognosis, while in multivariate analysis, only low p27Kip1 expression were independent prognostic factors for both cancer specific survival and recurrence-free survival in patients with RCC.

Conclusion

Our results suggest that immunohistochemical expression levels of p27Kip1, Skp2 and Cks1 may serve as markers with prognostic value in renal cell carcinoma.
Breast cancer proteomics reveals correlation between estrogen receptor status and differential phosphorylation of PGRMC1
Authors: Neubauer Hans , Clare Susan E , Wozny Wojciech , Schwall Gerhard P , Poznanović Slobodan , Stegmann Werner , Vogel Ulrich , Sotlar Karl , Wallwiener Diethelm , Kurek Raffael , Fehm Tanja , Cahill Michael A
Published: October 2008

Introduction

Breast tumors lacking the estrogen receptor-α (ER-α) have increased incidence of resistance to therapy and poorer clinical prognosis.

Methods

Whole tissue sections from 16 cryopreserved breast cancer tumors that were either positive or negative for the ER (eight ER positive and eight ER negative) were differentially analyzed by multiplex imaging of two-dimensional PAGE gels using 54 cm isoelectric focusing. Differentially detected spots of Progesterone Receptor Membrane Component 1 (PGRMC1) were shown to differ in phosphorylation status by differential two dimensional polyacrylamide gel electrophoresis of phosphatase-treated tumor proteins. Site directed mutagenesis was used to create putative phosphorylation site point mutants in PGRMC1. Stable transfectants of these mutants in MCF7 cells were assayed for their survival after oxidative stress, and for AKT kinase phosphorylation. Immune fluorescence using anti-PGRMC1 monoclonal antibody 5G7 was performed on breast cancer tissue microarrays.

Results

Proteins significantly differentially abundant between estrogen receptor negative and estrogen receptor positive tumors at the 0.1% level were consistent with published profiles, suggesting an altered keratin pool, and increased inflammation and wound responses in estrogen receptor negative tumors. Two of three spots of PGRMC1 were more abundant in estrogen receptor negative tumors. Phosphatase treatment of breast tumor proteins indicated that the PGRMC1 isoforms differed in their phosphorylation status. Simultaneous mutation of PGRMC1 serine-56 and serine-181 fully abrogated the sensitivity of stably transfected MCF7 breast cancer cells to peroxide-induced cell death. Immune fluorescence revealed that PGRMC1 was primarily expressed in ER-negative basal epithelial cells of mammary ductules. Even in advanced tumors, high levels of ER or PGRMC1 were almost mutually exclusive in individual cells. In five out of five examined ductal in situ breast cancers of comedo type, PGRMC1 was expressed in glucose transporter 1 negative or positive poorly oxygenated cells surrounding the necrotic core, surrounded by a more distal halo of ER-positive cells.

Conclusions

PGRMC1 phosphorylation may be involved in the clinical differences that underpin breast tumors of differing ER status.
Integrated 2D 4-C OBC velocity analysis of near-seafloor sediments, Green Canyon, Gulf of Mexico
Authors: DeAngelo Michael V. , Murray Paul E. , Hardage Bob A. , Remington Randy L.
Published: October 2008

Using 2D four-component ocean-bottom-cable (2D 4-C OBC) seismic data processed in common-receiver gathers, we developed robust [Formula: see text] and [Formula: see text] interval velocities for the near-seafloor strata. A vital element of the study was to implement iterative interpretation techniques to correlate near-seafloor P-P and P-SV images. Initially, depth-equivalent P-P and P-SV layers were interpreted by visually matching similar events in both seismic modes. Complementary 1D ray-tracing analyses then determined interval values of subsea-floor [Formula: see text] and [Formula: see text] velocities across a series of earth layers extending from the seafloor to below the base of the hydrate stability zone (BHSZ) to further constrain these interpretations. Iterating interpretation of depth-equivalent horizons with velocity analyses allowed us to converge on physically reasonable velocity models. Simultaneous [Formula: see text] and [Formula: see text] velocity analysis provided additional model constraints in areas where data quality of one reflection mode (usually [Formula: see text] in the near-seafloor environments) would not provide adequate information to derive reliable velocity information.
Optimal seismic-data acquisition in very shallow waters: Surveys in the Venice lagoon
Authors: Baradello Luca , Carcione José M.
Published: October 2008

Acquiring large amounts of data in very shallow waters of the immediate subtidal zone using a multichannel technique is unaffordable because moveout correction and a standard stacking procedure are required. The conventional inline longitudinal deployment of source and streamer leads to a phase difference along the hydrophone array for nonvertical arrivals. The array in this system is hard wired, so these phase differences cannot be accounted for and the summed output is attenuated as a result. We propose a transverse configuration, whereby the variation in phase along the array is smaller. The summed output improves because pairs of hydrophones with equivalent absolute offset are stacked in phase as a result of the symmetric configuration; however, all of the hydrophones are out of phase in the conventional geometry. Even at depths of [Formula: see text], a better image is obtained. The technique has been used during surveys in the Venice lagoon, where the water depth ranges from [Formula: see text].
Inverse-vector approach for smoothing dips and azimuths
Authors: Wang Yuchun Eugene , Luo Yi , Alfaraj Mohammed
Published: October 2008

We have explored a new approach for smoothing volumetric seismic dips and azimuths. This method iterates through a loop of three steps: (1) set a guide direction, (2) invert opposite vectors, and (3) average vectors and update the guide. This inverse-vector method can overcome instabilities where the gradient structure tensor approach fails — namely, when a dominant eigenvalue does not exist and the wrong eigenvector is selected to determine orientation. Inverse-vector smoothing is simple to implement and computationally efficient. The resultant dips and azimuths are consistent spatially and thus are more interpretable and suitable for calculating curvature and other dip-based attributes.
Near-surface attenuation estimation using wave-propagation modeling
Authors: El Yadari Nizare , Ernst Fabian , Mulder Wim
Published: October 2008

The effect of the near surface on seismic land data can be so severe that static corrections are insufficient. Full-waveform inversion followed by redatuming may be an alternative, but inversion will work only if the starting model is sufficiently close to the true model. As a first step toward determining a viscoelastic near-surface model, we assume that existing methods can provide a horizontally layered velocity and density model. Because near-surface attenuation is strongest, we propose a method to estimate the P-wave attenuation based on viscoacoustic finite-difference modeling. We compare energy decay along traveltime curves of reflection and refraction events in the modeled and observed seismic data for a range of attenuation parameters. The best match provides an estimate of the attenuation. First, we estimate only the attenuation of the top layer and study the sensitivity to depth and velocity perturbations. Then, we consider multiple layers. We apply the method to synthetic and real data and investigate the effect of source wavelet and topography. The method is robust against depth and velocity perturbations smaller than 10%. The results are sensitive to the source wavelet. Incorporating the surface topography in the computed traveltimes reduces the uncertainty of the attenuation estimates, especially for deeper layers.
The Classification and Treatment of Dysthymia
Authors: Murphy D. G. M.
Published: October 2008

The diagnostic concept and classification of chronic depressions has long been a matter of controversy. Kraepelin (1921) considered chronic depression to be a ‘rudiment’ of fully developed manic-depressive insanity, and this view was shared by Slater & Roth (1969), who cited occasional dramatic improvement in patients with neurasthenic disorder when they received convulsive therapy.
The Nithsdale Schizophrenia Surveys. VIII: Do Relatives Want Family Intervention – And Does It Help?
Authors: McCreadie R. G. , Phillips K. , Harvey J. A. , Waldron G. , Stewart M. , Baird D.
Published: October 2008

Sixty-three relatives of 52 schizophrenics living at home were offered a package of treatments by professionals working in an everyday NHS setting: educational seminars, relatives' groups, and family meetings. Thirty-two relatives refused intervention. Of the 31 relatives who agreed, 14 attended neither the educational seminars nor the relatives' groups. Seventeen relatives had a mean of ten treatment sessions, but there was little change in their level of expressed emotion after intervention. The number of patients who relapsed was the same in the 18 months before and after intervention, although the total number of relapses fell after intervention.

British Journal of Psychiatry (1991), 158, 110–113
Replacing the Mental Hospital
Authors: Kingdon David , Turkington Douglas , Malcolm Katy , Szulecka Krystyna , Larkin Emmett
Published: October 2008

Eighteen long-stay patients from an old county asylum moved into hospital hostels. After 12–24 months, there were significant reductions in overall symptoms, as rated by the CPRS and the Krawiecka scale, as well as in deviant but not general behaviour, rated by the REHAB scale. Six later moved to live in supported accommodation. All relatives and patients who expressed an opinion to an independent assessor were satisfied with their present accommodation or wished to move to more independent living.
Adversity in Groups with an Increased Risk of Minor Affective Disorder
Authors: Bebbington P. E. , Tennant C. , Hurry J.
Published: October 2008

The hypothesis that the sociodemographic distribution of minor affective disorder can be explained by high-risk groups experiencing more psychosocial stress, defined in terms of life events and chronic difficulties, was tested. Linear logistic analysis of data from 275 subjects identified in a community psychiatric survey provided little support for this. Although high-risk groups uniformly experienced more psychosocial adversity, and adversity was strongly associated with disorder, this did not provide an adequate explanation for the increased risk of disorder. This must therefore be explained in other ways.