bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetically Abnormal Circulating Cells in Lung Cancer Patients: An Antigen-Independent Fluorescence In situ Hybridization–Based Case-Control Study
Authors: Katz Ruth L. , He Weigong , Khanna Abha , Fernandez Ricardo L. , Zaidi Tanweer M. , Krebs Matthew , Caraway Nancy P. , Zhang Hua-Zhong , Jiang Feng , Spitz Margaret R. , Blowers David P. , Jimenez Carlos A. , Mehran Reza J. , Swisher Stephen G. , Roth Jack A. , Morris Jeffrey S. , Etzel Carol J. , El-Zein Randa
Published: July 2010

Purpose: We performed a study to determine if a fluorescence in situ hybridization (FISH)–based assay using isolated peripheral blood mononuclear cells (PBMCs) with DNA probes targeting specific sites on chromosomes known to have abnormalities in non–small cell lung cancer (NSCLC) cases could detect circulating genetically abnormal cells (CACs).

Experimental Design: We evaluated 59 NSCLC cases with stage I through IV disease and 24 controls. PBMCs and matched tumors were hybridized with 2 two-color [3p22.1/CEP3 and 10q22.3 (SP-A)/CEP10) and 2 four-color [CEP3, CEP7, CEP17, and 9p21.3 (URO); and EGFR, c-MYC, 6p11-q11, and 5p15.2 (LAV)] FISH probes. Percentages of cytogenetically abnormal cells (CACs) in peripheral blood and in matched tumor specimens were quantified by using an automated fluorescent scanner. Numbers of CACs were calculated based on the percentage of CACs (defined as PBMCs with genetic abnormalities) per milliliter of blood and expressed per microliter of blood.

Results: Patients with NSCLC had significantly higher numbers of CACs than controls. Mean number of CACs ranged from 7.23 ± 1.32/μL for deletions of 10q22.3/CEP10 to 45.52 ± 7.49/μL for deletions of 3p22.1/CEP3. Numbers of CACs with deletions of 3p22.1, 10q22.3, and 9p21.3, and gains of URO, increased significantly from early to advanced stage of disease.

Conclusions: We have developed a sensitive and quantitative antigen-independent FISH-based test for detecting CACs in peripheral blood of patients with NSCLC, which showed a significant correlation with the presence of cancer. If this pilot study can be validated in a larger study, CACs may have a role in the management of patients with NSCLC. Clin Cancer Res; 16(15); 3976–87. ©2010 AACR.
A Mutated Soluble Neuropilin-2 B Domain Antagonizes Vascular Endothelial Growth Factor Bioactivity and Inhibits Tumor Progression
Authors: Geretti Elena , van Meeteren Laurens A. , Shimizu Akio , Dudley Andrew C. , Claesson-Welsh Lena , Klagsbrun Michael
Published: July 2010

Neuropilins (NRP1 and NRP2) are coreceptors for vascular endothelial growth factor (VEGF) and mediate angiogenesis and tumor progression. VEGF binds to the NRP1 and NRP2 B domains. Previously, it was shown that mutagenesis of the soluble NRP2 B domain (MutB-NRP2) increased affinity to VEGF by 8-fold. Here, we show that MutB-NRP2 inhibited 125I-VEGF binding to NRP1, NRP2, and VEGFR-2. It antagonized VEGF-induced VEGFR-2/NRP2 complex formation and inhibited VEGF-induced activation of AKT, a mediator of cell survival, without affecting activation of VEGFR-2. In three-dimensional embryoid bodies, a model of VEGF-induced angiogenesis, MutB-NRP2 inhibited VEGF-induced sprouting. When overexpressed in human melanoma cells, MutB-NRP2 inhibited tumor growth compared with control tumors. Avastin (bevacizumab), a monoclonal antibody to VEGF, inhibited VEGF interactions with VEGFR-2, but not with NRPs. The combination of MutB-NRP2 and Avastin resulted in an enhanced inhibition of human melanoma tumor growth compared with MutB-NRP2 treatment only or Avastin treatment only. In conclusion, these results indicate that MutB-NRP2 is a novel antagonist of VEGF bioactivity and tumor progression. Mol Cancer Res; 8(8); 1063–73. ©2010 AACR.
Novel Function of Tenascin-C, a Matrix Protein Relevant to Atherosclerosis, in Platelet Recruitment and Activation Under Flow
Authors: Schaff Mathieu , Receveur Nicolas , Bourdon Catherine , Wurtz Virginie , Denis Cécile V. , Orend Gertraud , Gachet Christian , Lanza François , Mangin Pierre H.
Published: July 2010

Objective—

The identification of platelet-reactive proteins exclusively present in atherosclerotic plaques could provide interesting targets for effective and safe antithrombotic strategies. In this context, we explored platelet adhesion and activation to tenascin-C (TN-C), a matrix protein preferentially found within atheroma.

Methods and Results—

We show that platelets efficiently adhere to TN-C under both static and flow conditions. Videomicroscopy revealed a unique behavior under flow, with platelets exhibiting stationary adhesion to TN-C; in contrast, platelets rolled over von Willebrand factor and detached from fibrinogen. Platelet interaction with TN-C was predominantly supported by integrin α
2
β
1
under static conditions, whereas under high shear, it was dependent on both the α
2
β
1
integrin and the glycoprotein Ib-IX complex. Integrin α
IIb
β
3
appeared to play a secondary role but only at low shear rates. The glycoprotein Ib-IX–dependent interaction was indirect, relying on von Willebrand factor, and increased as a function of wall shear rate. Von Willebrand factor bound directly to TN-C, as shown by ELISA and coimmunoprecipitation, suggesting that it acts as a bridge between TN-C and platelets. The adhesion of platelets to TN-C triggered their activation, as demonstrated by a shape change and increases in intracellular calcium level.

Conclusion—

This study provides evidence that TN-C serves as a novel adhesive matrix for platelets in a context that is relevant to atherothrombosis.
TRAF5 Deficiency Accelerates Atherogenesis in Mice by Increasing Inflammatory Cell Recruitment and Foam Cell Formation
Authors: Missiou Anna , Rudolf Philipp , Stachon Peter , Wolf Dennis , Varo Nerea , Aichele Peter , Colberg Christian , Hoppe Natalie , Ernst Sandra , Münkel Christian , Walter Carina , Sommer Benjamin , Hilgendorf Ingo , Nakano Hiroyasu , Bode Christoph , Zirlik Andreas
Published: July 2010

Rationale:

Tumor necrosis factor receptor–associated factors (TRAFs) are cytoplasmic adaptor proteins for the TNF/interleukin-1/Toll-like receptor superfamily. Ligands of this family comprise multiple important cytokines such as TNFα, CD40L, and interleukin-1β that promote chronic inflammatory diseases such as atherosclerosis. We recently reported overexpression of TRAF5 in murine and human atheromata and that TRAF5 promotes inflammatory functions of cultured endothelial cells and macrophages.

Objective:

This study tested the hypothesis that TRAF5 modulates atherogenesis in vivo.

Methods and Results:

Surprisingly, TRAF5
−/−
/LDLR
−/−
mice consuming a high-cholesterol diet for 18 weeks developed significantly larger atherosclerotic lesions than did TRAF5
+/+
/LDLR
−/−
controls. Plaques of TRAF5-deficient animals contained more lipids and macrophages, whereas smooth muscle cells and collagen remained unchanged. Deficiency of TRAF5 in endothelial cells or in leukocytes enhanced adhesion of inflammatory cells to the endothelium in dynamic adhesion assays in vitro and in murine vessels imaged by intravital microscopy in vivo. TRAF5 deficiency also increased expression of adhesion molecules and chemokines and potentiated macrophage lipid uptake and foam cell formation. These findings coincided with increased activation of JNK and appeared to be independent of TRAF2. Finally, patients with stable or acute coronary heart disease had significantly lower amounts of TRAF5 mRNA in blood compared with healthy controls.

Conclusions:

Unexpectedly, TRAF5 deficiency accelerates atherogenesis in mice, an effect likely mediated by increased inflammatory cell recruitment to the vessel wall and enhanced foam cell formation.
Microbleeds and the Risk of Recurrent Stroke
Authors: Thijs Vincent , Lemmens Robin , Schoofs Christophe , Görner Astrid , Van Damme Philip , Schrooten Maarten , Demaerel Philippe
Published: July 2010

Background and Purpose—

We studied the risk of recurrent cerebrovascular events in patients who had a transient ischemic attack or ischemic stroke and who had evidence of microbleeds on MRI.

Methods—

A prospective follow-up study was performed on hospitalized patients who were at least 50 years old with a transient ischemic attack or an ischemic stroke. The presence and number of microbleeds were assessed on gradient echo MRI and the presence of white matter disease on fluid-attenuated inversion recovery imaging using a semiquantitative scale. Patients were followed up by phone every 6 months. End points were intracerebral hemorrhage, ischemic stroke, and unclassified stroke. Cerebral events were adjudicated by 2 independent neurologists blinded to the presence of microbleeds. Cox regression analysis was performed.

Results—

A total of 487 patients with a mean age of 72 years were followed up for a median of 2.2 years (25th to 75th percentile 1.9 to 2.7 years). Microbleeds were identified in 129 patients (25.6%). Two patients developed intracerebral hemorrhage during follow-up, 32 patients developed recurrent ischemic stroke, and 3 patients had unclassified strokes. Microbleeds were not independent predictors of recurrent stroke (
P
=0.2) or intracerebral hemorrhage (
P
=0.43). Lobar microbleeds or combined lobar and deep microbleeds were independently associated with recurrent stroke (
P
=0.018).

Conclusion—

In this European cohort, patients with microbleeds who have had cerebral ischemia have a higher risk of developing new ischemic strokes than of intracerebral hemorrhage. Lobar microbleeds or combined lobar and deep microbleeds might be independent predictors of recurrent stroke.
Blood Pressure Variability and Risk of New-Onset Atrial Fibrillation
Authors: Webb Alastair J.S. , Rothwell Peter M.
Published: July 2010

Background and Purpose—

Increased visit-to-visit variability in blood pressure (BP) is a powerful risk factor for stroke, but the mechanism is uncertain. We hypothesized that BP variability might affect the risk of new atrial fibrillation (AF).

Methods—

We did a systematic review of large randomized controlled trials reporting new-onset AF by treatment allocation, excluding studies in heart failure and acute myocardial infarction. Estimates of the risk of new AF by treatment allocation were related to effects of treatment on group variability in BP.

Results—

Of 94 eligible randomized controlled trials, 14 reported rates of new AF. Although there was considerable heterogeneity between trials in effects of treatment on variance ratio (
P
<0.0001), lower variance ratio was unrelated to new-onset AF either on meta-analysis (OR=1.02; 95% CI 0.90 to 1.15; 125 878 patients; 13 comparisons) or on metaregression (log OR versus log variance ratio of systolic blood pressure
r
2
=0.109,
P
=0.270). Angiotensin receptor blockers tended to reduce new-onset AF (OR 0.85; 95% CI 0.71 to 1.01;
P
=0.067; 4 trials; 47 482 patients) with significant reductions in 2 individual trials but had no consistent reduction on variability in BP.

Conclusions—

Effects of randomized treatment on variability in BP are unrelated to risk of new-onset AF, suggesting that other mechanisms account for the link between variability and stroke risk. However, a lower incidence of AF in patients randomized to angiotensin receptor blockers may explain reductions in stroke risk in some trials.
Introduction
Authors: Gregg Benjamin
Published: July 2010

I introduce the five articles in this special issue of Comparative Sociology as each applies the theory of enlightened localism. First I outline the theory in question and then highlight those aspects that each of the authors deploys, the criticisms each levels at it, and the suggestions each offers toward its improvement. Lea Ypi applies the theory to human rights in a way that might reconcile universal norms with the need for individual motivation that can only be local. Jonathan White uses the theory to develop a conception of the European Union that would preserve rather than, as now, repress the partisan politicking at the core of democracy. Junmin Wang finds the theory helpful in analyzing the unintended decentralization of political power in China as a consequence of recent economic reforms. Ko Hasegawa seeks an enlightened localist solution to the problematic integration of a minority population into mainstream Japanese society. Manuel Ahedo enlists the theory in combating ghettoized schooling all too typical for immigrant children in Europe with ideas for integrating the children of immigrants with those of long-established residents. I conclude by listing some of the questions raised by the articles and to be addressed by future research ‐ concerns that might move an enlightened localist approach forward.
Gender Justice in a Prayer: American Muslim Women’sExegesis, Authority, and Leadership
Authors: Hammer Juliane
Published: July 2010

The 2005 woman-led Friday prayer in New York City generated broad media attention and significant levels of intra-Muslim debates about women’s inclusion in mosques, gender roles, and textual interpretation. This essay examines the prayer event within the larger context of American Muslim women’s contributions to reinterpretations of the Qur’an and their negotiations of religious authority, leadership roles, and mosque spaces in a North American context. The essay is based on the writings of American Muslim women on gender discourses and on media coverage, documentaries, and Internet sources produced by and about them. I argue that some of the initiatives toward gender inclusiveness in American mosques and communities should be read as an embodiment of gender-just interpretations of the Qur’an, and as products of particularly American and transnational constellations of Muslim discourses on gender. Another women’s ‘sit-in’ at the Islamic Center in Washington, D.C., in February of 2010 serves as an epilogue to the essay.
Circumventing Uncertainty in the Moral Economy: West African Shrines in Europe, Witchcraft and Secret Gambling
Authors: Parish Jane
Published: July 2010

This paper examines the moral economy of the African Diaspora through the illicit activities of secret Ghanaian gamblers in Europe. It follows a Ghanaian, Mr. Baba, a gambler, from North West England, who looks to the most unlikely of sources of information and certainty in a fast networked society, the Akan anti-witchcraft shrine located not in Ghana but in the eastern suburbs of Paris, as global bookmaker extraordinaire. In this environment, the anti-witchcraft shrine rather than being a traditional, obsolete relic of a superstitious past is in its supersonic element. It is able to transmit ‘hidden’ data, a valuable exchange commodity in an uncertain and insecure age, about betting odds on an infinite range of topics. At the same time, simultaneously, it protects this commodity from the grasp of witches ‐ immoral, female figures who link fraudulent facts to the relations that people have with one another.
Effect of electron irradiation on structure of carbon nanotubes
Authors: Xu Z W , Min C Y , Chen L , Wang Y K , Guo Q W , Wu N
Published: July 2010

The present paper reviews the basic effects of electron beam irradiation on the structure of carbon nanotubes (CNTs). The production of irradiation induced defects and their migration in CNTs are introduced, and the influence of irradiation on the structural transformation and dimension of CNTs is discussed. It is shown that the change in incident electron energy, ambient temperature and tube wall number will lead to the different irradiation results. It is expected that electron irradiation studies will continue to play an important role in the research on CNTs.
Semisolid processing of short and long freezing range Cu alloys by electric current
Authors: Prodhan A
Published: July 2010

The present study reports the effect of ac (50 Hz) electric current treatment (ECT) on short freezing range (Cu–Ni) and long freezing range (Cu–Sn) alloys. This treatment was conducted during the semisolid state of the alloys, i.e. during casting in sand moulds. In isomorphous Cu–Ni alloy, with gradual increase in the electric current, first, the dendrites are refined; then, the refined dendrites are fragmented; and finally, the fragmented dendrites are refined. The ECT also reduces homogenisation treatment time. It is observed that a small amount of electric energy spent during sand casting saves considerable amount of energy for homogenisation treatment. The sand castings of Cu–Sn (peritectic) alloys are very much prone to interdendritic shrinkage. Thus, the density of castings is reduced. However, the ECT during casting increases the density of castings by reducing interdendritic shrinkage, modifies phase diagram of Cu–Sn alloy, increases volume fraction of the primary α phase (Cu) and reduces volume fraction of the peritectic phase. The ECT also refines the peritectic phase that transforms to δ phase on cooling to room temperature.
A germline gain-of-function mutation in Ptpn11 (Shp-2) phosphatase induces myeloproliferative disease by aberrant activation of hematopoietic stem cells
Authors: Xu Dan , Wang Siying , Yu Wen-Mei , Chan Gordon , Araki Toshiyuki , Bunting Kevin D. , Neel Benjamin G. , Qu Cheng-Kui
Published: July 2010

Germline and somatic gain-of-function mutations in tyrosine phosphatase PTPN11 (SHP-2) are associated with juvenile myelomonocytic leukemia (JMML), a myeloproliferative disease (MPD) of early childhood. The mechanism by which PTPN11 mutations induce this disease is not fully understood. Signaling partners that mediate the pathogenic effects of PTPN11 mutations have not been explored. Here we report that germ line mutation Ptpn11D61G in mice aberrantly accelerates hematopoietic stem cell (HSC) cycling, increases the stem cell pool, and elevates short-term and long-term repopulating capabilities, leading to the development of MPD. MPD is reproduced in primary and secondary recipient mice transplanted with Ptpn11D61G/+ whole bone marrow cells or purified Lineage−Sca-1+c-Kit+ cells, but not lineage committed progenitors. The deleterious effects of Ptpn11D61G mutation on HSCs are attributable to enhancing cytokine/growth factor signaling. The aberrant HSC activities caused by Ptpn11D61G mutation are largely corrected by deletion of Gab2, a prominent interacting protein and target of Shp-2 in cell signaling. As a result, MPD phenotypes are markedly ameliorated in Ptpn11D61G/+/Gab2−/− double mutant mice. Collectively, our data suggest that oncogenic Ptpn11 induces MPD by aberrant activation of HSCs. This study also identifies Gab2 as an important mediator for the pathogenic effects of Ptpn11 mutations.
How I treat Diamond-Blackfan anemia
Authors: Vlachos Adrianna , Muir Ellen
Published: July 2010

Diamond-Blackfan anemia (DBA) is characterized by red cell failure, the presence of congenital anomalies, and cancer predisposition. In addition to being an inherited bone marrow failure syndrome, DBA is also categorized as a ribosomopathy as, in more than 50% of cases, the syndrome appears to result from haploinsufficiency of either a small or large subunit-associated ribosomal protein. Nonetheless, the exact mechanism by which haploinsufficiency results in erythroid failure, as well as the other clinical manifestations, remains uncertain. New knowledge regarding genetic and molecular mechanisms combined with robust clinical data from several international patient registries has provided important insights into the diagnosis of DBA and may, in the future, provide new treatments as well. Diagnostic criteria have been expanded to include patients with little or no clinical findings. Patient management is therefore centered on accurate diagnosis, appropriate use of transfusions and iron chelation, corticosteroids, hematopoietic stem cell transplantation, and a coordinated multidisciplinary approach to these complex patients.
Simultaneous prediction of transcription factor binding sites in a group of prokaryotic genomes
Authors: Zhang Shaoqiang , Li Shan , Pham Phuc T , Su Zhengchang
Published: July 2010

Background

Our current understanding of transcription factor binding sites (TFBSs) in sequenced prokaryotic genomes is very limited due to the lack of an accurate and efficient computational method for the prediction of TFBSs at a genome scale. In an attempt to change this situation, we have recently developed a comparative genomics based algorithm called GLECLUBS for de novo genome-wide prediction of TFBSs in a target genome. Although GLECLUBS has achieved rather high prediction accuracy of TFBSs in a target genome, it is still not efficient enough to be applied to all the sequenced prokaryotic genomes.

Results

Here, we designed a new algorithm based on GLECLUBS called extended GLECLUBS (eGLECLUBS) for simultaneous prediction of TFBSs in a group of related prokaryotic genomes. When tested on a group of γ-proteobacterial genomes including E. coli K12, a group of firmicutes genomes including B. subtilis and a group of cyanobacterial genomes using the same parameter settings, eGLECLUBS predicts more than 82% of known TFBSs in extracted inter-operonic sequences in both E. coli K12 and B. subtilis. Because each genome in a group is equally treated, it is highly likely that similar prediction accuracy has been achieved for each genome in the group.

Conclusions

We have developed a new algorithm for genome-wide de novo prediction of TFBSs in a group of related prokaryotic genomes. The algorithm has achieved the same level of accuracy and robustness as its predecessor GLECLUBS, but can work on dozens of genomes at the same time.
Troglitazone suppresses telomerase activity independently of PPARγ in estrogen-receptor negative breast cancer cells
Authors: Rashid-Kolvear Fariborz , Taboski Michael AS , Nguyen Johnny , Wang Dong-Yu , Harrington Lea A , Done Susan J
Published: July 2010

Background

Breast cancer is one the highest causes of female cancer death worldwide. Many standard chemotherapeutic agents currently used to treat breast cancer are relatively non-specific and act on all rapidly dividing cells. In recent years, more specific targeted therapies have been introduced. It is known that telomerase is active in over 90% of breast cancer tumors but inactive in adjacent normal tissues. The prevalence of active telomerase in breast cancer patients makes telomerase an attractive therapeutic target. Recent evidence suggests that telomerase activity can be suppressed by peroxisome proliferator activated receptor gamma (PPARγ). However, its effect on telomerase regulation in breast cancer has not been investigated.

Methods

In this study, we investigated the effect of the PPARγ ligand, troglitazone, on telomerase activity in the MDA-MB-231 breast cancer cell line. Real time RT-PCR and telomerase activity assays were used to evaluate the effect of troglitazone. MDA-MB-231 cells had PPARγ expression silenced using shRNA interference.

Results

We demonstrated that troglitazone reduced the mRNA expression of hTERT and telomerase activity in the MDA-MB-231 breast cancer cell line. Troglitazone reduced telomerase activity even in the absence of PPARγ. In agreement with this result, we found no correlation between PPARγ and hTERT mRNA transcript levels in breast cancer patients. Statistical significance was determined using Pearson correlation and the paired Student's t test.

Conclusions

To our knowledge, this is the first time that the effect of troglitazone on telomerase activity in breast cancer cells has been investigated. Our data suggest that troglitazone may be used as an anti-telomerase agent; however, the mechanism underlying this inhibitory effect remains to be determined.
A yeast-based genomic strategy highlights the cell protein networks altered by FTase inhibitor peptidomimetics
Authors: Porcu Giampiero , Wilson Cathal , Di Giandomenico Daniele , Ragnini-Wilson Antonella
Published: July 2010

Background

Farnesyltransferase inhibitors (FTIs) are anticancer agents developed to inhibit Ras oncoprotein activities. FTIs of different chemical structure act via a conserved mechanism in eukaryotic cells. They have low toxicity and are active on a wide range of tumors in cellular and animal models, independently of the Ras activation state. Their ultimate mechanism of action, however, remains undetermined. FTase has hundred of substrates in human cells, many of which play a pivotal role in either tumorigenesis or in pro-survival pathways. This lack of knowledge probably accounts for the failure of FTIs at clinical stage III for most of the malignancies treated, with the notable exception of haematological malignancies. Understanding which cellular pathways are the ultimate targets of FTIs in different tumor types and the basis of FTI resistance is required to improve the efficacy of FTIs in cancer treatment.

Results

Here we used a yeast-based cellular assay to define the transcriptional changes consequent to FTI peptidomimetic administration in conditions that do not substantially change Ras membrane/cytosol distribution. Yeast and cancer cell lines were used to validate the results of the network analysis. The transcriptome of yeast cells treated with FTase inhibitor I was compared with that of untreated cells and with an isogenic strain genetically inhibited for FTase activity (Δram1). Cells treated with GGTI-298 were analyzed in a parallel study to validate the specificity of the FTI response. Network analysis, based on gene ontology criteria, identified a cell cycle gene cluster up-regulated by FTI treatment that has the Aurora A kinase IPL1 and the checkpoint protein MAD2 as hubs. Moreover, TORC1-S6K-downstream effectors were found to be down-regulated in yeast and mammalian FTI-treated cells. Notably only FTIs, but not genetic inhibition of FTase, elicited up-regulation of ABC/transporters.

Conclusions

This work provides a view of how FTIs globally affect cell activity. It suggests that the chromosome segregation machinery and Aurora A association with the kinetochore as well as TORC1-S6K downstream effectors are among the ultimate targets affected by the transcriptional deregulation caused by FTI peptidomimetics. Moreover, it stresses the importance of monitoring the MDR response in patients treated with FTIs.
Characterization of the TnsD-attTn7 complex that promotes site-specific insertion of Tn7
Authors: Mitra Rupak , McKenzie Gregory J , Yi Liang , Lee Cherline A , Craig Nancy L
Published: July 2010

The bacterial transposon Tn7 is distinguished by its ability to recognize a specific site called attTn7, and insert just downstream of the highly conserved chromosomal glmS gene. TnsD is one of four transposon-encoded polypeptides (TnsABC+D) required for site-specific insertion of Tn7 into attTn7, and is the target site-selector that binds to a highly conserved sequence in the end of the glmS protein coding region. In this study, we identified important nucleotides within this region that are crucial for TnsD-attTn7 interaction. We also probed the regions of TnsD that interact with attTn7 and found that there are important DNA-binding determinants throughout the entire length of the protein, including an amino-terminal CCCH zinc-finger motif. A key role of TnsD is to recruit the non-sequence specific DNA-binding protein TnsC to attTn7; TnsC also interacts with and controls both the TnsA and TnsB subunits of the Tn7 transposase. TnsC stimulates the binding of TnsD to attTn7 in vivo, and TnsCD and TnsD can also interact in the absence of DNA and localize their interaction domains to the N-terminal region of each protein.
Adenoid cystic carcinoma of the breast in the United States (1977 to 2006): a population-based cohort study
Authors: Ghabach Bassam , Anderson William F , Curtis Rochelle E , Huycke Mark M , Lavigne Jackie A , Dores Graça M
Published: July 2010

Introduction

Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and special type of basal-like tumor for which scant population-based descriptive data exist. We sought to provide new population-based information on breast-ACC incidence, relative survival, and associated cancer risk in the United States.

Methods

Using data from the Surveillance, Epidemiology and End Results Program, we calculated age-adjusted incidence rates (IRs), IR ratios (IRRs), and relative survival for breast-ACC, and standardized incidence ratios (SIRs) for other cancers.

Results

Overall 338 women (IR = 0.92/1 million person-years) were diagnosed with breast-ACC during 1977 to 2006. Blacks had 39% lower IRs than Whites (IRR = 0.61, 95% confidence interval = 0.37 to 0.96), and IRs remained constant over the 30-year period. Ninety-five percent of cases presented with localized stage (n = 320; IR = 0.87), and the highest IRs were observed for estrogen receptor (ER)-negative/progesterone receptor (PR)-negative tumors (IR = 0.56). Like other typically ER-negative tumors, age-specific IRs increased until midlife and then plateaued. Five-year, 10-year, and 15-year relative survival was 98.1%, 94.9%, and 91.4%, respectively. The risk of female breast cancer was not increased following (SIR = 0.89, 95% confidence interval = 0.43 to 1.64) or preceding (SIR = 0.71, 95% confidence interval = 0.28 to 1.46) breast-ACC. Similarly, no association was observed for breast-ACC and risk of all other cancers combined, solid tumors, or lymphohematopoietic malignancies.

Conclusions

Breast-ACC among women is characterized by ER-negative/PR-negative expression, rare regional lymph node involvement, a favorable prognosis with excellent survival, and absence of associated cancers. These findings reinforce the importance of tailored treatments for breast-ACC and lend credence to the apparent heterogeneity of basal-like breast cancers.
Turning limited experimental information into 3D models of RNA
Authors: Flores Samuel Coulbourn , Altman Russ B.
Published: July 2010

Our understanding of RNA functions in the cell is evolving rapidly. As for proteins, the detailed three-dimensional (3D) structure of RNA is often key to understanding its function. Although crystallography and nuclear magnetic resonance (NMR) can determine the atomic coordinates of some RNA structures, many 3D structures present technical challenges that make these methods difficult to apply. The great flexibility of RNA, its charged backbone, dearth of specific surface features, and propensity for kinetic traps all conspire with its long folding time, to challenge in silico methods for physics-based folding. On the other hand, base-pairing interactions (either in runs to form helices or isolated tertiary contacts) and motifs are often available from relatively low-cost experiments or informatics analyses. We present RNABuilder, a novel code that uses internal coordinate mechanics to satisfy user-specified base pairing and steric forces under chemical constraints. The code recapitulates the topology and characteristic L-shape of tRNA and obtains an accurate noncrystallographic structure of theTetrahymenaribozyme P4/P6 domain. The algorithm scales nearly linearly with molecule size, opening the door to the modeling of significantly larger structures.
Effects of Lipid‐Lowering Therapy on Reduction of Cardiovascular Events in Patients with End‐Stage Renal Disease Requiring Hemodialysis
Authors: Marrs Joel C. , Saseen Joseph J.
Published: July 2010

In the general population, dyslipidemia is an established independent risk factor for cardiovascular disease. In patients with end‐stage renal disease (ESRD), comorbid cardiovascular disease is present at alarming rates, and those who require hemodialysis and have cardiovascular disease continue to have a high mortality rate. Lipid abnormalities associated with chronic kidney disease (CKD) vary depending on the stage of disease (stages 1–5), but low‐density lipoprotein cholesterol (LDL) has been established as the primary lipid treatment target. Guidelines support an LDL level of less than 100 mg/dl in patients with all stages of CKD, except when the triglyceride level is above 500 mg/dl. As patients progress to stage 5 CKD (ESRD with hemodialysis), the high triglyceride, low high‐density lipoprotein cholesterol, and increased lipoprotein(a) levels of the early stages become more pronounced, with increases in small dense LDL particles; however, total cholesterol and LDL values remain normal or decrease. In patients undergoing hemodialysis, lipid abnormalities are driven by an increase in hepatic secretion and delayed catabolism of very low‐density lipoproteins, as well as a reduction in lipoprotein lipase and hepatic lipase. Epidemiologic data support the role of cholesterol lowering as a means to lower cardiovascular events in the hemodialysis population. We conducted a literature search of various databases (1966–September 2009) to identify relevant clinical trials that evaluated the efficacy and safety of multiple lipid‐lowering agents for the treatment of dyslipidemia in patients with ESRD requiring hemodialysis. Only those trials that used clinical primary end points of coronary heart disease (e.g., cardiovascular death, myocardial infarction, stroke) were included in this review. Evidence demonstrates that 3–hydroxy‐3–methylglutaryl coenzyme A reductase inhibitor (statin) therapy (i.e., atorvastatin and rosuvastatin) significantly reduces surrogate cardiovascular markers, particularly LDL, in patients with ESRD requiring hemodialysis; however, no statin has proved to reduce cardiovascular morbidity or mortality in this population. Trials evaluating omega‐3 fatty acids did not show significant reductions in LDL or cardiovascular events in this population. Clinicians should appreciate these limitations when deciding whether to continue lipid‐lowering pharmacotherapy in these patients, depending on their overall cardiovascular risk assessment.
Pharmacologic Options for Reducing the Shivering Response to Therapeutic Hypothermia
Authors: Weant Kyle A. , Martin Julia E. , Humphries Roger L. , Cook Aaron M.
Published: July 2010

Recent literature has demonstrated significant improvements in neurologic outcomes in patients who have received induced hypothermia in the setting of out‐of‐hospital cardiac arrest. Through multiple metabolic mechanisms, the induction of hypothermia slows the progression and devastation of transient cerebral hypoxia. Despite these benefits, the desired reduction in core temperature is often a challenging venture as the body attempts to maintain homeostasis through the induction of thermoregulatory processes aimed at elevating body temperature. Shivering is an involuntary muscular activity that enhances heat production in an attempt to restore homeostasis. For successful induction and maintenance of induced hypothermia, shivering, as well as other thermoregulatory responses, must be overcome. Several pharmacologic options are available, either used alone or in combination, that safely and effectively prevent or treat shivering after the induction of hypothermia. We conducted a PubMed search (1966–March 2009) to identify all human investigations published in English that discussed pharmacologic mechanisms for the control of shivering. Among these options, clonidine, dexmedetomidine, and meperidine have demonstrated the greatest and most clinically relevant impact on depression of the shivering threshold. More research in this area is needed, however, and the role of the clinical pharmacist in the development and implementation of this therapy needs to be defined.
Intrapleural Tissue Plasminogen Activator for the Treatment of Parapneumonic Effusion
Authors: Hamblin Susan E. , Furmanek Douglas L.
Published: July 2010

Intrapleural tissue plasminogen activator (t‐PA) has emerged over the past several years as a treatment option for patients with complicated parapneumonic effusion that does not respond to medical management and drainage. Fibrinolytics are thought to dissolve fibrin deposits and loculations within the pleural space, facilitating drainage of the trapped pleural fluid surrounding the lungs. Whereas older fibrinolytics (streptokinase and urokinase) have been studied for intrapleural use with conflicting results, t‐PA is currently the agent most commonly used in adults for this indication. However, the literature describing t‐PA therapy for complicated parapneumonic effusion and empyema is sparse, and studies have been highly variable in their methods. Several articles report use of this drug at doses ranging from 2–100 mg at daily intervals or more frequently. Surgical treatment options associated with good outcomes are also available to these patients. As a result, the indications for intrapleural t‐PA (especially compared with surgical management) in patients with effusions resistant to conventional drainage are not fully clear. The usefulness of t‐PA in all patients with resistant parapneumonic effusions or empyema before surgical intervention remains undetermined, but several studies have taken this approach. Sufficient evidence is available to indicate that this therapy does have potential in patients for whom surgery is not a safe or desired option. Further study is needed to better understand the role of t‐PA and its optimal dosage in patients with complicated parapneumonic effusion.
Platinum Group Metals Research from a Global Perspective
Authors: Gavin Helen
Published: July 2010

Analysis of the non-patent scientific literature can be used to reveal trends in platinum group metals (pgms) research. In this article, a study was carried out using the Chemical Abstracts database on key terms related to the pgms for the years 1998 and 2008, revealing an increase in research during this time period across most of the pgms both globally and especially in China. Platinum and ruthenium showed the most growth with areas such as nanotechnology and magnetic memory becoming particularly significant for ruthenium. In China, the fields of electrochemistry, and energy conversion technologies including fuel cells, were among those showing growth.
Nurse Dose: Validation and Refinement of a Concept
Authors: Sidani Souraya , Manojlovich Milisa , Covell Christine
Published: July 2010

In this article, we report the results of two studies aimed at validating the concept of nurse dose. The first study examined the relevance of the critical attributes and empirical indicators in accurately reflecting the concept of nurse dose. Ten experts in staffing research rated the relevance of the attributes and indicators. The second study explored the factorial structure of the nurse dose concept. Data on the nurse dose indicators were obtained from 26 inpatient units. The operationalization of nurse dose was refined based on the two studies’ results. Nurse dose is posited as a structural variable capturing nurses’ capacity to deliver high quality care in acute care hospitals. It is defined as the level (i.e., number and type) of nursing staff required to provide care that produces intended patient outcomes. Nurse dose is reflected in two attributes: (1) active ingredients representing the essential elements that distinguish nurses from other health care professionals and operationalized in nurses’ theoretical and practical knowledge, and skill mix; and (2) intensity representing the potential for nurse–patient interactions and operationalized in terms of amount (indicated by full-time equivalent) and frequency (indicated by nurse–patient ratio and hours per patient day). The concept of nurse dose has the potential for guiding future staffing research.
Theory of Planned Behavior, Self-Care Motivation, and Blood Pressure Self-Care
Authors: Peters Rosalind M. , Templin Thomas N.
Published: July 2010

The theory of planned behavior (TPB) was integrated within the theory of self-care (SCT) to explore the predictive value of extending TPB to measure attitudes and beliefs regarding a behavioral goal, and determine the ability of goal beliefs to predict engagement in the combined, multiple behaviors necessary to control BP. The hypothesized model was evaluated in a sample of 306 community-dwelling African Americans between 21 and 65 years of age. Scales developed for the study achieved acceptable reliability (α = .68–.95). Structural equation modeling analysis resulted in a second-order factor structure with attitude, subjective norm, perceived behavioral control, and intention modeled as indicators of a construct representing goal beliefs related to keeping BP within normal limits. This latent construct was conceptualized within the theory of self-care as “self-care motivation,” and predicted 18% of the variance in self-care behaviors necessary for BP control. The model achieved acceptable fit (CMIN/ df = 2.32; CFI = .95; RMSEA = .066). Final assessment of fit was done using multi-group SEM and bootstrapping techniques. In this extension of the TPB attitudes and beliefs regarding the goal of keeping BP within normal limits were found to determine one’s motivation to engage in the multiple behaviors necessary for BP control.
Predictors of Condom Use Among Mexican Adolescents
Authors: Alvarez Carmen , Villarruel Antonia M. , Zhou Yan , Gallegos Esther
Published: July 2010

Mexican adolescents continue to be at increased risk for HIV infection due to inconsistent condom use. The purpose of this study was to identify predictors of condom use intentions and condom use among Mexican adolescents who participated in a randomized control trial designed to test a sexual-risk reduction intervention. Data from sexually active adolescents 17 to 21 years (n = 157) of age who were assigned to the control group were analyzed 48 months post intervention. Regression analysis showed that positive attitudes toward condoms, subjective norms, and control beliefs significantly explained intention to use condoms (R2 = .75, p < .001). Attitudes toward condoms (β = .67, p < .001), technical skills (β = .13, p = .01), and condom use self-efficacy (β = .24, p < .001) were significant predictors of condom use intention. Compared to those who inconsistently used condoms, adolescents who used condoms consistently had greater intention to use condoms and greater impulse control. Findings suggest that attitudes and control beliefs should be further explored with Mexican adolescents in order to support consistent condom use.
Providing Care for Underserved Patients: Periodontists' and Periodontal Residents' Educational Experiences, Attitudes, and Behaviors
Authors: Garfinkle Adam J. , Richards Philip S. , Inglehart Marita R.
Published: July 2010

Background: Patients with special health care needs (SHCNs) and patients from underrepresented minority and/or low socioeconomic backgrounds are more likely to have problems accessing oral health care services. The objectives of this study are: 1) to explore how well the dental education of periodontists prepared them to treat these underserved patients, 2) to assess related professional attitudes and confidence when treating these patients as well as professional behaviors, and 3) whether educational experiences are related with attitudes, confidence, and behaviors in this context.

Methods: Survey data were collected from a randomly selected sample of 291 members of the American Academy of Periodontology (AAP) and 64 periodontal residents.

Results: Overall, large percentages of residents agreed that their predoctoral and graduate dental educations had prepared them well to treat patients with special needs (predoctoral education: 58%; clinical graduate education: 45%; and classroom‐based graduate education: 37%), from different ethnic/racial backgrounds (predoctoral education: 74%; clinical graduate education: 74%; and classroom‐based graduate education: 60%), and on Medicaid (predoctoral education: 60%; clinical graduate education: 61%; and classroom‐based graduate education: 42%). Practicing clinicians were least positive about their educations. Students were more positive about treating patients on Medicaid and pro bono cases than practicing clinicians. However, the two groups did not differ in their confidence when treating underserved patients. The quality of predoctoral and graduate educations regarding underserved patients correlates with the attitudes, confidence, and behaviors of providers concerning providing care for these patients.

Conclusions: The findings of this study stress the importance of preparing future periodontists in their predoctoral and graduate programs for providing care for underserved patients such as patients with SHCNs. The better that dental education prepares future periodontists to provide care for underserved patients, the more confident periodontists will be when encountering these patients in their own practices and the more likely they will be to contribute to reducing disparities in oral health care access in the United States by treating these patients.
6. Multivariable Hilbert-Type Integral Inequalities
Authors: Yang Bicheng
Published: July 2010

In this chapter, we consider a class of multivariable Hilbert-type integral inequalities and the
reverses, which are the best extensions of the corresponding results in Chapter 2. We also consider some
equivalent integral inequalities with the non-homogeneous kernels and the Hardy-type integral inequalities.
Index
Authors: Yang Bicheng
Published: July 2010

Full text available
Macroeconomic Effects of HIV/AIDS Prevalence and Policy in Nigeria: A Simulation Analysis
Authors: Abdulsalam Sikiru
Published: July 2010

This study develops a macroeconometric model of the Nigerian economy to examine the potential impact of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) on key macroeconomic outcomes in Nigeria. The baseline model of the Nigerian economy is estimated using data from 1980 to 2000. The simulated values of key endogenous macroeconomic outcomes are shown to closely follow actual historical data and also future macroeconomic outcomes from 2001 to 2006. Simulations are conducted to examine (1) the potential effects of an increase in HIV/AIDS prevalence and (2) the potential effects of increased government expenditure for treatment and prevention of HIV. The simulations show increased HIV/AIDS prevalence will reduce output in the agriculture and manufacturing sectors and will have little or even a positive effect on output in the oil and gas sector. The simulations also show that increased government spending on HIV treatment and prevention will increase output across all industries; however, it will reduce gross fixed capital formation and capital expenditures.
Fundamental groups and Diophantine geometry
Authors: Kim Minhyong
Published: July 2010

This is a brief exposition on the uses of non-commutative fundamental groups in the study of Diophantine problems.