bluuebunny/crossref_metadata_2025_split huggingface dataset:
HuR's role in gemcitabine efficacy: an exception or opportunity?
Authors: Brody Jonathan R. , Gonye Gregory E. 
Published: November 2010

AbstractOver the next few years, research teams will focus on, and millions of dollars will be spent on, sorting through cancer genomes. Undoubtedly, ‘druggable’ targets and events will be discovered that will improve our understanding and, hopefully, treatment of cancer. Highlighting an alternative to this ‘genome‐centric’ approach, this review will further explore an underappreciated mechanism of gene expression regulation, posttranscription mRNA:protein interactions. A key molecule involved in this mode of gene regulation is HuR and we have shown that HuR levels and HuR cellular distribution can predict how pancreatic cancer patients responded to the standard of care chemotherapy (i.e., gemcitabine). HuR regulates post‐transcriptional processes through: (1) association with specific mRNA cargos with ARE‐rich sequences and (2) stress‐induced increased cytoplasmic protein levels. Over multiple laboratories and diverse tumor types, it has been shown that HuR supports tumor survival through its regulation of tumor‐promoting transcripts such as VEGF. In this article, we will highlight a recent discovery that this potent post‐transcriptional gene regulatory mechanism has an impact on a common chemotherapeutic, gemcitabine. Specifically, we have identified the mechanism by which HuR can regulate a key gemcitabine metabolic enzyme, deoxycytidine kinase. We will use this example to explore and hypothesize the functional roles that HuR may have on anticancer drug therapies. We will survey novel high throughput global gene expression analysis tools to discover novel HuR targets. Future multidisciplinary approaches focused on HuR biology will provide critical events and ‘druggable’ targets in cancer that large‐scale genomic sequencing efforts will miss. WIREs RNA 2011 2 435–444 DOI: 10.1002/wrna.62This article is categorized under:

RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition
RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
RNA in Disease and Development > RNA in Disease
RNA Methods > RNA Analyses In Vitro and In Silico
Of Tubs and Toil: Kohler Workers in an Empire of Hygiene, 1920–2000
Authors: Oberdeck Kathryn J. 
Published: December 2010

SummaryThis paper examines contests over the intimate and global geographies of domestic hygiene advanced by the Kohler Company, a plumbing-ware manufacturer that promoted “American” standards living in its welfare-capitalist industrial village of Kohler, Wisconsin. Drawing from the approaches of labor history, cultural history, and critical geography, it demonstrates the value of combining these methodologies. The perspectives of Kohler workers on “American” living standards, it reveals, complicate cultural histories that cast such workers as uncritical audiences for imperializing claims about the superiority of American sanitation. The paper argues that workers who struggled to unionize the Kohler plant challenged company definitions of “American” standards and generated alternative, laborite maps of domestic hygiene and the labor associated with it among local immigrant workers and laborers elsewhere in the world. It considers the legacy of those maps in the context of the company’s changing global networks of production and consumption.
The Mid-Atlantic Islands: A Theatre of Early Modern Ecocide?
Authors: Halikowski Smith Stefan 
Published: December 2010

SummaryThe Iberian rediscovery of the mid-Atlantic islands in the late Middle Ages was accompanied by all kinds of utopian projections. However, within a hundred years, both human and animal populations were made extinct, and the rich forest cover was rapidly depleted for cash-cropping industries, primarily sugar. Historians view the migration of the international sugar industry from the mid-Atlantic islands to Brazil as an example of expanding economies of scale, but contemporary accounts indicate what now might be called widespread ecocide as a major contributing factor. This essay looks at the environmental ramifications of the sugar industry as well as other cultures, and assesses whether it is indeed appropriate to speak of ecocide in the context of the mid-Atlantic islands in the early modern period.
The Colonial Famine Plot: Slavery, Free Trade, and Empire in the French Atlantic, 1763–1791
Authors: Horan Joseph 
Published: December 2010

SummaryThis essay examines the use of famine-plot rhetoric in the course of disputes over free trade in the French Atlantic during the late eighteenth century. Seeking to discredit officially sanctioned trade monopolies, French plantation owners frequently suggested that the control exercised by metropolitan merchants over transatlantic commerce was responsible for food shortages among the enslaved population of the colonies. In reality, the planters themselves bore primary responsibility for malnutrition in the French Caribbean, thanks to their reliance on the slave trade and support for the expansion of plantation agriculture. While proponents of the colonial famine plot accepted that plantation slavery had made it impossible for the resources available in the colonies to sustain the growing enslaved population, they remained committed to the plantation system. In advocating expanded free trade as the best means to ensure the continued growth of the colonies, French planters anticipated a response to the environmental problems caused by colonial expansion that became increasingly prevalent among proponents of European imperialism during the nineteenth century.
CONTRACT, COVENANT, CONSTITUTION
Authors: Lomasky Loren E. 
Published: November 2010

AbstractContract is the dominant model for political philosophy's understanding of government grounded on the consent of the governed. However, there are at least five disabilities attached to classical social contract theory: (1) the grounding contract never actually occurred; (2) its provisions are vague and contestable; (3) the stringency of the obligation thereby established is dubious; (4) trans-generational consent is questionable; (5) interpretive methods for giving effect to the contract are ill-specified. By contrast, the biblical story of the covenant Israel embraces at Sinai is shown to be more adequately attentive to each of these five desiderata. The essay then focuses on the U.S. Constitution, arguing that in many ways it is more reflective of covenantal legitimating themes than those of social contract. The result is a promisingly different mode of understanding government by the consent of the governed.
CONSTITUTIONALISM IN THE AGE OF TERROR
Authors: Zuckert Michael , Valenzuela Felix 
Published: November 2010

AbstractThe threat of terrorism once again raises some of the classic questions about constitutionalism: is it possible for constitutions to do what they aim to do—channel and control political power in such a way as to make it safe and beneficent for those under its rule but also competent to govern? Does not terrorism reraise the Schmittian problem of “the exception”, i.e., the situation of emergency that necessarily escapes all constitutional limitations? Although they did not face the problem of terrorism as we know it, the American founders developed three different models of constitutionalism, embodying three different ways of responding to emergent circumstances and yet remaining bound to the constitutionalist aspiration. We develop the main outlines of the three models both conceptually and historically and show how they continue to be relevant to current discussions of constitutionalism in the age of terror. Finally, we make a tentative effort to judge which of the three models is most able to do what constitutions should do in difficult times.
DELIBERATIVE DEMOCRACY AND CONSTITUTIONS
Authors: Fishkin James S. 
Published: November 2010

AbstractThis paper examines the potential role of deliberative democracy in constitutional processes of higher law-making, either for the founding of constitutions or for constitutional change. It defines deliberative democracy as the combination of political equality and deliberation and situates this form of democracy in contrast to a range of alternatives. It then considers two contrasting processes—elite deliberation and plebiscitary mass democracy (embodied in referenda) as approaches to higher law-making that employ deliberation without political equality or political equality without deliberation. It finally turns to some institutional designs that might achieve both fundamental values at the same time, or in the process of realizing a sequence of choices.
THE CONSTITUTION OF NONDOMINATION
Authors: Pincione Guido 
Published: November 2010

AbstractPincione argues that procedural constitutional guarantees of market freedoms best protect individuals from domination. If he is right, Philip Pettit's claim that various forms of state interference with private markets are needed to forestall domination will prove to be unwarranted. Pincione further contends that market freedoms are best protected by procedural rules for political decision-making, as opposed to constitutional guarantees of private property and other substantive rules.Central to his position are claims that the dispersion of economic power precludes domination, and that free entry into markets furthers such dispersion. As against the idea that the state is in a better position to disperse economic power, Pincione argues that the constitutional provisions needed to implement that idea are contestable, and to that extent require interpretive powers that themselves involve domination. Only a constitution that, as a side effect of its procedures for political decision making, generates full private property rights holds out hope of shielding citizens from domination. This is so, because a plurality of suppliers of goods and services is a structural feature of the free market, in a sense of “structural” that matters for measurements of domination based on fairly uncontroversial claims about persons and resources.
Germination characteristics of Syngonanthusseeds (Eriocaulaceae) incampos rupestresvegetation in south-eastern Brazil
Authors: Oliveira Patrícia G. , Garcia Queila S. 
Published: November 2010

AbstractThe present study evaluated the size and germination characteristics of seeds of seven species ofSyngonanthus(distributed among four sections) that occur in different microhabitats incampos rupestresvegetation in Minas Gerais State, to determine if (1) the germination responses of the various species characterize a single germination pattern for the genus; and (2) there is a correlation between the germination characteristics and the geographic distribution as well as the microhabitat of the different species. The experiments were undertaken with recently collected seeds exposed to a 12-h photoperiod and continuous darkness, at constant temperatures of 10–40°C (at intervals of 5°C) in germination chambers. The results indicated the existence of a pattern of reduced seed size and light requirements for germination within the genus. The geographic distribution of different species of the genus cannot be explained by the responses of seed germination to different temperatures, but suggests some relationship to their edaphic microhabitats. Therefore, germination characteristics of the populations studied may have been selected to colonize specific environments at different soil water conditions.
Extra-cranial Stereotactic Radiation Therapy (ESRT) in the treatment of inoperable stage 1 & 2 non-small-cell lung cancer patients with highly mobile tumours: a literature review
Authors: Tooke Emily W. , Roe Benjamin 
Published: November 2010

AbstractObjective: Extra-cranial Stereotactic Radiation Therapy (ESRT) techniques and equipment utilised in the treatment of Stage 1 or 2 inoperable non-small-cell lung cancer (NSCLC); accounting for Respiratory Induced Tumour Motion (RITM).Methods: A narrative review of current world literature.Results: Four main strategies are employed to address RITM: (1) tumour movement minimisation/immobilisation; (2) integration of respiratory movements into planning; (3) respiratory-gating techniques; and (iv) tumour-tracking techniques.Discussion: Analysis of data gathered suggests that due to inherent difficulties with respiratory function, combined with co-morbidities and the level of dose escalation facilitated by ESRT: techniques that do not require patient ability to comply are more likely to be effective with a wider range of patients. Similarly, treatment planning must incorporate accurate four-dimensional (4D) data to ensure target coverage, although setup and verification should be controlled to smaller margins for error.Conclusion: The disparate nature of reporting methods restricts statistical comparison. However, this paper suggests that the ESRT technique using abdominal compression (AC), free-breathing respiratory-gating (FBRG), 4D computed tomography (4DCT) planning, combined with daily on board kV cone beam computed tomography (CBCT) imaging for setup and target verification, is a possible candidate for further treatment regime assessments in large multi-centre trials.
Immune responses to heat shock protein in Porphyromonas gingivalis‐infected periodontitis and atherosclerosis patients
Authors: Chung Sung‐Woon , Kang Ho‐Sung , Park Hae‐Ryoun , Kim Sung‐Jo , Kim Soo‐Jin , Choi Jeom‐Il 
Published: November 2010

Background:  It has been widely thought that heat shock protein might be involved in autoimmune disease mechanisms in humans.Objectives:  The present study was performed to evaluate the recognition of Porphyromonas gingivalis heat shock protein 60 (hsp60) and human hsp60 by immune sera in P. gingivalis‐infected periodontitis and atherosclerosis patients.Materials and methods:  Mononuclear cells from atheroma lesions were stimulated with P. gingivalis hsp and sera from periodontitis or atherosclerosis patients were subjected to Western immunoblotting to P. gingivalis hsp or human hsp, respectively.Results:  Western immunoblot analysis demonstrated the dual reactivity of anti‐P. gingivalis antisera with P. gingivalis hsp and human hsp. We could also establish P. gingivalis hsp‐specific T cell lines from the atheroma lesions, a mixture of CD4+ and CD8+ cells producing the cytokines characteristic of both Th1 and Th2 subsets.Conclusion:  These observations suggest the modulating effect of P. gingivalis hsp60 in the immunopathogenesis of periodontitis and atherosclerosis.
Expression of endothelin‐1 in gingival epithelial cells
Authors: Yamamoto Eri , Awano Shuji , Koseki Takeyoshi , Ansai Toshihiro , Takehara Tadamichi 
Published: November 2010

Objectives and background:  Endothelin‐1 (ET‐1) is a 21‐amino acid peptide with multifunctional regulation. ET‐1 expresses in various cells during inflammation. The present study aimed to examine the ET‐1 expression in oral epithelial cells after infection with the periodontal pathogen and to investigate the presence of ET‐1 in human inflamed and uninflamed gingival tissues.Materials and methods:  The KB cells were infected with Porphyromonas gingivalis and the expression level of ET‐1 was examined using reverse transcription‐polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA). The immunohistochemical analysis of ET‐1 was performed in gingival tissues obtained from patients. In addition, the ET‐1 mRNA expression in each tissue was also investigated by RT‐PCR.Results:  The expression of ET‐1 in KB cells was strongly induced by the P. gingivalis infection. On the other hand, the strong immunoreactivity for ET‐1 was observed in the epithelium and vascular endothelial cells of the inflamed gingival tissue. Furthermore, the level of ET‐1 mRNA was greater in the inflamed tissues.Conclusion:  These results suggested that the expression level of ET‐1 in gingival epithelial cells might be enhanced during the periodontal inflammation.
Molecular analysis of promoter region of the SMN2 gene in the patients of spinal musculatr atrophy.
Authors: Baig Atif , Shamsudin Watihayati , Marzuki Marini , Hayati Fatemeh , Suriano Teguh , Yean Chan , Manicam Ravichandran , Alwi Zilfalil 
Published: November 2010

AbstractSpinal muscular atrophy (SMA) is a neurodegenerative disorder caused by the absence of the full length SMN protein (FL-SMN) as a result of mutation or deletion of SMN1 gene. The isoform to this gene, SMN2 gene, with mutation in 1 base pair, encodes for 10% of FL-SMN protein and is reported to decrease the severity of the disease when there is an increase gene dosage. There are 3 clinical types of SMA; type I, type II and type III. Type I SMA is the most severe type and only a small amount of FL-SMN protein is present in these individuals. We postulated that the difference in the promoter region of SMN2 gene produces the different level of FL-SMN protein. To verify this hypothesis, the DNA samples of 69 SMA patients who were referred to the Human Genome Center, USM were extracted from their blood. The SMN1 deletion analysis was performed, followed by the SMN2 copy no. analysis and NAIP deletion analysis to remove any clinical bias as NAIP gene deletion and SMN2 copy number have been reported to be associated with SMA disease severity. Only 10 SMA patients from different clinical types (type I=2, type II=3, type III=5) with homozygous deletion of the SMN1 and 2 copies of the SMN2 and deletion in NAIP were finally recruited. Primers were designed for the amplification of the SMN2 promoter region. Bioinformatics analysis was performed to identify the crucial transcription factor binding sites within the reported ~4.6 kb promoter region. As the core promoter region is still unknown (unreported), we analyzed 15 ORFs and 24 nested ORFs with 15 TATA boxes reflecting the diverse functional integrity of this region. The promoter prediction and core promoter prediction was also performed. Based on the bioinformatics analysis and the designed primers, PCR amplification was done for different regions in the promoter and the PCR products were subjected to direct DNA sequencing. The results were analyzed by Vector NTI suite 9, ClustalX and Gene Doc softwares. The molecular analysis confirmed the absence of any mutation in the promoter region of the SMN2 gene between normal healthy individuals (total 2) and SMA patients. In 4 patients and 1 normal healthy individual the CA repeats were found to be increased which we think cause no effect in disease progression and severity. In conclusion, there was no mutation found in the promoter region of the SMN2 gene among the SMA patients of different clinical types and normal controls. Further analysis involving the cloning of the promoter regions with highest probability of involvement in expression of the SMN2 gene using luciferase assay is ongoing. The results will be useful for the subsequent phase of the study involving the transcription initiation of the SMN2 gene.
New Lewis Structures through the application of the Hypertorus Electron Model
Authors: Yepez Omar 
Published: November 2010

AbstractThe hypertorus electron model is applied to the chemical bond. As a consequence, the bond topology can be determined. A linear correlation is found between the normalized bond area and the bond energy. The normalization number is a whole number. This number is interpreted as the Lewis's electron pair. A new electron distribution in the molecule follows. This discovery prompts to review the chemical bond, as it is understood in chemistry and physics.
The Effect of Urbanization on Bumble Bee Communities in Greater Philadelphia
Authors: Malfi Rosemary , Williams Neal 
Published: November 2010

AbstractBumble bees (Bombus spp.) are among the most important wild pollinators in temperate ecosystems in North America and Europe, and are believed to be vital to the functioning of the pollination networks in which they occur. Accordingly, evidence of their overall decline in Europe and more selective decline in the U.S. has raised concern about the long term persistence of many species. Human-induced changes in land use, including the loss of natural and semi-natural habitat and associated floral resources, are purported causes in several cases. Declines prompted an investigation of this potential trend in the urbanized landscape in and surrounding Philadelphia, PA. We surveyed the species richness and abundance of bumble bee communities in ten half-ha plots located in restored, managed meadows along a gradient of urban and suburban development in the Philadelphia metropolitan area from June 1 to August 15, 2006. In conjunction with collections, we measured floral density within each plot. We calculated the proportion of developed land at differing spatial scales ranging from 500 to 4000 m from survey sites. General linear models were used to test the effect of developed land, local meadow size, and floral resource density on overall bumble bee species richness and abundance.Development did not have any detectable effect on species richness at any tested spatial scale. Bee abundance was best explained by a model that included the proportion of developed land at the 2500 m scale. In contrast to our expectations, total bumble bee abundance was significantly higher in plots with a higher proportion of developed land surrounding the site (F1,5 = 8.13, P = 0.04). Local floral density did not significantly affect richness or abundance (F 1,5 = 0.93, P = 0.34), nor was local resource quality associated with development (r = 0.52, P = 0.12) . We hypothesize that gardens maintained in urban and suburban landscapes may provide an important and consistent food supply to bumble bees throughout the duration of their colony cycle. Forested habitats, which were the other dominate habitat type, may actually be relatively poor in bumble bee resources following closure of the canopy in late spring. This research indicates that restored meadows are excellent habitat for bumble bees and may promote pollination services in urbanized settings.
In silico Genetic Network Models for *Pre-clinical Drug Prioritization
Authors: Xiong Jianghui , Liu Juan , Rayner Simon , Tian Ze , Li Yinghui , Chen Shanguang 
Published: November 2010

AbstractThe high rates of failure in oncology drug clinical trials highlight the problems of using pre-clinical data to predict the clinical effects of drugs. Patient population heterogeneity and unpredictable physiology complicate pre-clinical cancer modeling efforts. We hypothesize that gene networks associated with cancer outcome in heterogeneous patient populations could serve as a reference for identifying drug effects. Here we propose a novel in vivo genetic interaction which we call ‘synergistic outcome determination’ (SOD), a concept similar to ‘Synthetic Lethality’. SOD is defined as the synergy of a gene pair with respect to cancer patients' outcome, whose correlation with outcome is due to cooperative, rather than independent, contributions of genes. The method combines microarray gene expression data with cancer prognostic information to identify synergistic gene-gene interactions that are then used to construct interaction networks based on gene modules (a group of genes which share similar function). In this way, we identified a cluster of important epigenetically regulated gene modules. By projecting drug sensitivity-associated genes on to the cancer-specific inter-module network, we defined a perturbation index for each drug based upon its characteristic perturbation pattern on the inter-module network. Finally, by calculating this index for compounds in the NCI Standard Agent Database, we significantly discriminated successful drugs from a broad set of test compounds, and further revealed the mechanisms of drug combinations. Thus, prognosis-guided synergistic gene-gene interaction networks could serve as an efficient in silico tool for pre-clinical drug prioritization and rational design of combinatorial therapies.