bluuebunny/crossref_metadata_2025 huggingface dataset:
Quick Screening Method for the Photocatalytic Activity of Textile Fibers and Fabrics
Authors: Ritter Axel , Reifler Felix A. , Michel Elisabeth
Published: October 2009

A quantitative photometric screening method for the measurement of the degradation of formaldehyde by photocatalytic fibers and fabrics was developed. For quick screening, formaldehyde was chosen as an analyte because of its environmental relevance in indoor air pollution, its easy handling, common use and clear degradation pathway. The degradation of formaldehyde was measured quantitatively by a sensitive photometric method after irradiation in the presence of fibers or fabrics. This method allows a fast screening of produced fibers and fabrics with respect to their odor reduction capability. It is able to reveal the differences in the formaldehyde degradation capabilities of, for example, fibers with different titers as well as fibers or fabrics with various contents of the photocatalyst, titanium dioxide.
The Politics of Spinoza’s Vanishing Dichotomies
Authors: Oksenberg Rorty Amélie
Published: October 2009

Spinoza’s project of showing how the mind can be freed from its passive affects and the State from its divisive factions (E IV.Appendix and V.Preface) ultimately coincides with the aims announced in the subtitle of the Tractatus-Theologico-Politicus (TTP) “to demonstrate that [the] freedom to philosophize does not endanger the piety and obedience required for civic peace.”1 Both projects rest on a set of provisional isomorphic distinctions—between adequate and inadequate ideas, between reason and the imagination, between active and passive affects—that Spinoza proceeds to blur, and indeed to renounce. In using these distinctions while also moving to overcome them, Spinoza is not confused or indecisive. Every philosopher, every wise Sovereign, every free man who attempts to incorporate adequate ideas in inadequately framed, perspectivally limited contexts must use these distinctions and also see how deeply misleading they are. I want to offer a friendly amendment to Hasana Sharpe’s essay “The Force of Ideas in Spinoza” arguing that Spinoza refuses her distinction between the force of an idea and its truth.2
Interspecies Scaling of Therapeutic Monoclonal Antibodies: Initial Look
Authors: Ling Jie , Zhou Honghui , Jiao Qun , Davis Hugh M.
Published: October 2009

The authors evaluated interspecies scaling for the prediction of human clearance of 18 therapeutic monoclonal antibodies (mAbs). Human and monkey/chimpanzee data of 14 mAbs were classified based on the targeted antigens (soluble or membrane bound). Simple allometry and/or a time‐invariant method (elementary Dedrick plot) were performed. Results indicate that human clearance might be accurately predicted from monkey data for mAbs targeting soluble receptors or membrane‐bound receptors with limited tissue distribution using simplified allometry. The optimal exponents were estimated to be 0.85 or 0.90. If nonlinearity is anticipated at the human efficacious dose, pharmacokinetic parameters obtained at high doses in animals might not be sufficient for full pharmacokinetic characterization and prediction. Using prespecified criteria, including predicted human clearance (≤ or > 10 mL/d/kg), simplified allometric scaling might be helpful in predicting the effect of receptor‐mediated clearance for mAbs targeting membrane‐bound antigens. Furthermore, simplified allometry and an elementary Dedrick plot provide similar results in predicted clearance. Given the significant advantages offered by simplified allometry, it should be used when data are available from only 1 species. When reasonable data from ≥3 species are available, traditional allometry should be explored. Overall, clearance prediction is useful for human dose prediction in drug discovery and development.
Clinical Pharmacokinetics and Exposure‐Toxicity Relationship of a Folate‐Vinca Alkaloid Conjugate EC145 in Cancer Patients
Authors: Li Jing , Sausville Edward A. , Klein Patrick J. , Morgenstern David , Leamon Christopher P. , Messmann Richard A. , LoRusso Patricia
Published: October 2009

The clinical pharmacokinetics and exposure‐toxicity relationship were determined for EC145, a conjugate of folic acid and the Vinca alkaloid desacetylvinblastine hydrazide (DAVLBH), in cancer patients. EC145 plasma concentration and toxicity data were obtained from a first‐in‐man phase I study and analyzed by nonlinear mixed effect modeling with NONMEM. EC145 concentration‐time profile after intravenous administration was well described by a 2‐compartment model with a first‐order elimination process from the central compartment. BSA was identified as a significant covariate on EC145 clearance, accounting for 14.6% of interindividual variation on EC145 clearance. Population estimates for the clearance, steady‐state volume of distribution, distribution, and elimination half‐lives were 56.1 L/h, 26.1 L, 6 minutes, and 26 minutes, respectively. Constipation and peripheral neuropathy were the most common and clinically relevant toxicities. The clearance and area under the concentration‐time curve (AUC) were significant predictors for the incidence of EC145‐induced constipation but not peripheral neuropathy. In conclusion, EC145 is rapidly distributed and eliminated in cancer patients. BSA is a statistically significant covariate on EC145 clearance, but its clinical relevance remains to be defined. EC145‐induced constipation occurs at a higher frequency in the patients with lower EC145 clearance, where the drug exposure tends to be higher.
Influence of Development, HIV Infection, and Antiretroviral Therapies on the Gene Expression Profiles of ABC Transporters in Human Lymphocytes
Authors: Giraud Carole , Manceau Sandra , Declèves Xavier , Goffinet François , Morini Jean‐Pierre , Chappuy Hélène , Batteux Frédéric , Chouzenoux Sandrine , Scherrmann Jean‐Michel , Blanche Stéphane , Tréluyer Jean‐Marc
Published: October 2009

The efficacy of drugs acting on lymphocytes like anticancer, immunosuppressive, and antiretroviral drugs depends on their intracellular concentrations, which could be modulated by membrane efflux pumps belonging to the ABC transporter superfamily. The gene expression profiles of 6 main ABC transporters (MDR1, MRP1, MRP3, MRP4, MRP5, and BCRP) were established in lymphocytes from birth to adulthood using blood samples from 57 children and 15 adults (34 and 5 HIV‐infected, respectively). Gene expression levels were quantified by quantitative RT‐PCR. In adults, the MRP1 gene had the highest expression, followed by the MRP5 gene. BCRP and MRP4 genes were significantly higher expressed at birth than after 1 month of life. Neither HIV infection nor antiretroviral therapies modulated the gene expression profiles of ABC transporters. In conclusion, drugs that are substrates of BCRP and MRP4, like zidovudine, may have an altered efficacy in newborns.
Pedagogy and Place: Merging Urban and Environmental History with Active Learning
Authors: Corey Steven H.
Published: October 2009

Exposing undergraduates to history first-hand through the active learning process is an effective and rewarding way to help them learn about the evolution and nature of urban life.This article highlights the experience of an urban studies professor in implementing active learning models and inquiry-based exercises into four separate undergraduate courses; an interdisciplinary introductory course in urban studies, a survey course in American urban history, an upper-level class in environmental history and public policy, and a specialized course on community development and urban renewal. It argues that a wide variety of local sources can be used to illustrate larger urban trends and environmental themes while at the same time exciting students about becoming scholars, public policy professionals, and informed citizens.
The City and Public History
Authors: Wilson Gregory
Published: October 2009

Focusing on a course titled “History, Communities and Memory,” this article examines the course content, undergraduate and graduate student learning outcomes, and the pedagogical approaches employed throughout the semester. Using Akron’s engaging history and the portrayal of the city in public sites as a case study, the class serves as both an introduction to public history and to the interplay between history and memory. Arthur Chickering and Zelda Gamson’s seven principles for best practice inform the teaching methodologies discussed here, combined with a focus on critical thinking and civic engagement. The course content emphasizes how communities and historic sites present their history (or histories) and (following the work of Maurice Halbwachs) how memory operates simultaneously on both the individual level and the social one. The students employ Akron—especially its industrial past—to understand how the concepts and theories presented in the readings can be applied.
The pragmatic use of apomorphine at the end of life
Authors: Dewhurst F. , Lee M. , Wood B.
Published: October 2009

Parkinson’s Disease (PD) is an irreversible degenerative neurological disorder with no known cure. Apomorphine is a potent short-acting D1/D2 dopamine agonist administered sub-cutaneously that is used in the treatment of PD. Optimising PD medication is an important aspect of end of life care. There are no previously reported cases of apomorphine providing symptom relief in terminal care of PD patients. This case highlights its potential benefits for symptom control at the end of life.
Costs associated with resource utilization during the palliative phase of care: a Canadian perspective
Authors: Dumont Serge , Jacobs Philip , Fassbender Konrad , Anderson Donna , Turcotte Véronique , Harel François
Published: October 2009

Objective: This study aimed to evaluate prospectively the resource utilization and related costs during the palliative phase of care in five regions across Canada. Subjects: A cohort of 248 patients registered in a palliative care program and their main informal caregivers were consecutively recruited. Research Design: A prospective research design with repeated measures was adopted. Interviews were conducted at two-week intervals until the patient s passing or up to a maximum of 6 months. Measures: The survey questions prompted participants to provide information on the types and number of goods and services they used, and who paid for these goods and services. Results: The largest cost component for study participants was inpatient hospital care stays, followed by home care and informal caregiving time. In regard to cost sharing, the public health care system (PHCS), the family, and not-for-profit organizations (NFPO) sustained respectively 71.3%, 26.6%, and 1.6% of the mean total cost per patient. Conclusion: Such results provide a comprehensive picture of costs related to palliative care in Canada, by specifying the cost sharing between the PHCS, the family, and NFPO.
What progress has been made towards implementing national guidance on end of life care? A national survey of UK general practices
Authors: Hughes Philippa M , Bath Peter A , Ahmed Nisar , Noble Bill
Published: October 2009

The objectives of this study were to establish the extent to which UK primary care has adopted recommended practices on supportive and palliative care of adults with cancer, and to relate this to participation in national initiatives. We conducted a cross-sectional postal questionnaire survey of a random sample of UK general practices. In total, 60.0% of practices (2096 of 3495) responded to the survey: 61.5% reported involvement with the Gold Standards Framework (GSF); 24.4% with the Liverpool or other End of Life Care Pathway; 12.3%, with the Preferred Place of Care (PPC) initiative; and 8.4% with Advance Care Planning (ACP). Participation in GSF contributed most to the variance in practice organization scores; and practice organization scores contributed most to the variance in clinical care scores. Participation in ACP or PPC, and higher clinical care scores were associated with an increased likelihood of reported high rates of death at home for cancer patients. Our findings appear to support the role of national initiatives in improving the quality of end-of-life care delivery in general practice. A population-based study would be required to assess the effect of end of life care on clinical outcomes and patient or carer experience.
Can Melanie Klein Help Us Understand Morality in IR?
Authors: Gallagher Julia
Published: October 2009

This article explores the question of why states attempt to ‘do good’ or behave morally beyond their own borders. It draws on the conceptual model developed by the psychoanalyst Melanie Klein in her work on moral development. Klein suggested that children develop ways of dealing with moral ambiguity and guilt by projecting idealised forms of good and bad into the wider world beyond the family. There, they are separable from each other in ways that more complex, intense familial relationships do not allow, are safer to deal with because they are less bound up with personal identity and survival, enabling reparation of an internal sense of the good. The article explores how far Klein’s approach might provide a basis for thinking about state behaviour. Situating Klein within a communitarian framework, it argues that her ideas provide insight into the ways in which states might project good beyond the morally more complex community in order to reinforce a stronger sense of a ‘good state’. It explores the question of how far international normative behaviour is derived from a projection of domestic ideas of what is good; and how far the expression of good in the international context supports the development and safety of norms at home. These themes are discussed in relation to British policy in Africa between 1997 and 2007.
Kashmir Road
Authors: Booth W. James
Published: October 2009

In this article, I argue that an attention to the absent past, and its demands, is very much part of what we do when we do justice. I also urge that identity, the sense of a shared something, is dependent on memory as an ingathering of the past. Where the community sees grave injustice in that past, that too can come to be an active force in the present. The ways in which this often benign and familiar part of politics metamorphoses into memory-fueled political violence is at the centre of that analysis. My task here is not to judge that violence, either in general or in the particular (Northern Irish) illustrations I draw on. Rather, my goal is to move beyond a view of memory politics, including its violent dimensions, that sees it from the outset as a kind of profound irrationality or madness.
Child Slaves and Freemen at the Spiritan Mission in Soyo, 1880-1885
Authors: Vos Jelmer
Published: October 2009

Catholic missionaries in late nineteenth- and early twentieth-century Africa more commonly than Protestants purchased slaves to build their mission stations. This article provides a micro-historical analysis of the redemption of child slaves by the Holy Ghost Fathers in Soyo, West Central Africa, in the years immediately preceding the colonial partition of Africa. It argues that the Spiritan missionaries liberated slaves for instrumental rather than humanitarian reasons. As local freemen were difficult to control, the mission depended for its growth on the import of slave children. Furthermore, since the missionaries operated on the same markets and paid the same prices for slaves as regular buyers, their purchasing practices showed a strong resemblance with ordinary slave trading.
Flexural Strengthening of Reinforced Concrete Beams with Steel-reinforced Polymer Composites: Analytical and Computational Investigations
Authors: Kim Yail J. , Fam Amir , Green Mark F.
Published: October 2009

This article presents analytical and computational models for reinforced concrete beams strengthened in flexure using an emerging composite material, steel-reinforced polymer (SRP). The SRP composite consists of unidirectional high-carbon steel fabric embedded in a polymeric resin, providing high strength and stiffness at a reasonable cost. The models developed and examined include finite element analysis, strain compatibility analysis, and closed-form equations reported in the literature and design codes. The study focuses on the load—deflection and load—strain responses, strain variation along the SRP sheets, shear stress distributions and concentrations near the cut-off points of SRP sheets, and cracking behavior. In general, the study shows that flexural strength and deflection at service loads can be well predicted using the models. The shear stress concentration near the cut-off points of SRP sheets may be approximated to 10% of the resin tensile strength just prior to SRP delamination. Confining effects by the adequate end-anchorage effectively redistribute the applied stress in the strengthened beam.
Studying municipal solid waste generation and composition in the urban areas of Bhutan
Authors: Phuntsho Sherub , Dulal Ichharam , Yangden Dechen , Tenzin Ugyen M. , Herat Sunil , Shon Hokyong , Vigneswaran Saravanamuthu
Published: October 2009

Bhutan lacks the solid waste data which are essential parameters for planning and scheduling of municipal solid waste management (MSWM) systems. The first ever large-scale research survey on solid waste generation and characterization in the urban areas of Bhutan was conducted between November 2007 and January 2008 using the method of waste sampling at source. The MSW generation rates in the urban centres were 0.53 kg capita-1 day- 1, which consists predominantly of organic waste materials of up to 58% indicating a great opportunity for composting. Domestic waste from the households contributed the maximum (47%) component of the total MSW generated from the urban centres followed by wastes from the commercial establishments. Attempt to study the correlation between household monthly income and the waste per capita generation rates did not yield any conclusive result.
Effect of cohesion and fill amplification on seismic stability of municipal solid waste landfills using limit equilibrium method
Authors: Savoikar Purnanand , Choudhury Deepankar
Published: October 2009

Municipal solid waste (MSW) landfills in seismic zones are subjected to the seismic forces both in the horizontal and vertical directions. The stability of landfills against these seismic forces was evaluated by computing the factor of safety of landfills with different modes of failure among which failures of landfills due to translation are very common. Conventionally, the seismic stability of landfill is evaluated by using pseudo-static limit equilibrium method. In the present study, seismic stability of landfills is evaluated by both the conventional pseudo-static and modern pseudo-dynamic method. The pseudo-dynamic method is superior as it takes into account the effect of duration and frequency of earthquake motion and corresponding body waves in addition to the variation of earthquake accelerations along depth and time. In the present study, the effects of cohesion and fill amplification on seismic stability of landfill are also taken into account. It was noticed that, neglecting cohesion of fill material as well as liner material, results in a lower factor of safety and, hence, a very conservative/uneconomic design. Also, fill amplification is found to reduce the factor of safety values computed only by using the pseudo-dynamic method, showing its advantage. Generalized expressions are developed for factor of safety and yield acceleration against translational failure, which can be used for evaluating the seismic stability of MSW landfills. Comparisons of results under static condition with existing, similar methodology show a very good agreement. However, the present study seems to provide unique results for the seismic case.
Recycling of wood for particle board production: accounting of greenhouse gases and global warming contributions
Authors: Merrild Hanna , Christensen Thomas H.
Published: October 2009

The greenhouse gas (GHG) emissions related to the recycling of wood waste have been assessed with the purpose to provide useful data that can be used in accounting of greenhouse gas emissions. Here we present data related to the activities in a material recovery facility (MRF) where wood waste is shredded and foreign objects are removed in order to produce wood chips for use in the production of particleboard. The data are presented in accordance with the UOD (upstream, operational, downstream) framework presented in Gentil et al. ( Waste Management & Research, 27, 2009). The GHG accounting shows that the emissions related to upstream activities (5 to 41 kg CO2-equivalents tonne —1 wood waste) and to activities at the MRF (approximately 5 kg CO2-equivalents tonne—1 wood waste) are negligible compared to the downstream processing (—560 to —120 kg CO2equivalents tonne—1 wood waste). The magnitude of the savings in GHG emissions downstream are mainly related to savings in energy consumption for drying of fresh wood for particleboard production. However, the GHG account highly depends on the choices made in the modelling of the downstream system. The inclusion of saved electricity from avoided chipping of virgin wood does not change the results radically (—665 to —125 kg CO2-equivalents tonne— 1 wood waste). However, if in addition it is assumed that the GHG emissions from combustion of wood has no global warming potential (GWP) and that the energy produced from excess wood due to recycling substitutes energy from fossil fuels, here assumed to be coal, potentially large downstream GHG emissions savings can be achieved by recycling of waste wood (—1.9 to —1.3 tonnes CO2-equivalents tonne— 1 wood waste). As the data ranges are broad, it is necessary to carefully evaluate the feasibility of the data in the specific system which the GHG accounting is to be applied to.
Efficiency of energy recovery from municipal solid waste and the resultant effect on the greenhouse gas balance
Authors: Gohlke Oliver
Published: October 2009

Global warming is a focus of political interest and life-cycle assessment of waste management systems reveals that energy recovery from municipal solid waste is a key issue. This paper demonstrates how the greenhouse gas effects of waste treatment processes can be described in a simplified manner by considering energy efficiency indicators. For evaluation to be consistent, it is necessary to use reasonable system boundaries and to take the generation of electricity and the use of heat into account. The new European R1 efficiency criterion will lead to the development and implementation of optimized processes/systems with increased energy efficiency which, in turn, will exert an influence on the greenhouse gas effects of waste management in Europe. Promising technologies are: the increase of steam parameters, reduction of in-plant energy consumption, and the combined use of heat and power. Plants in Brescia and Amsterdam are current examples of good performance with highly efficient electricity generation. Other examples of particularly high heat recovery rates are the energy-from-waste (EfW) plants in Malmö and Gothenburg. To achieve the full potential of greenhouse gas reduction in waste management, it is necessary to avoid landfilling combustible wastes, for example, by means of landfill taxes and by putting incentives in place for increasing the efficiency of EfW systems.
Recycling of stone cutting sludge in formulations of bricks and terrazzo tiles
Authors: Al-Zboon Kamel , Tahat Montasser , Abu-Hamatteh Ziad S.H. , Al-Harahsheh Mohammad S.
Published: October 2009

This study examines the possibility for enhancing the use of stone cutting sludge waste in the production of building bricks and terrazzo tiles, which would reduce both the environmental impact and the production costs. Stone cutting wastes in the form of sludge is currently generated at several factories in Jordan. At the Samara factory, incorporation of the sludge in the batch formulations of bricks and terrazzo tiles was examined. The physicochemical and mineralogical characteristics of the sludge were analyzed to identify the major components. Results indicated that the sludge generated from stone cutting could be used in producing concrete bricks. Mixtures of aggregates with added amounts of sludge were used successfully to produce non-load bearing bricks. Sludge was also used to produce terrazzo tiles and the results indicate that the transverse strength, water absorption and tile measurements, for all the taken samples, comply with Jordanian standards. The transverse strength decreased while water absorption increased as the sludge ratio increased.
Global warming factors modelled for 40 generic municipal waste management scenarios
Authors: Christensen Thomas H. , Simion Federico , Tonini Davide , Møller Jacob
Published: October 2009

Global warming factors (kg CO2-eq.-tonne—1 of waste) have been modelled for 40 different municipal waste management scenarios involving a variety of recycling systems (paper, glass, plastic and organics) and residual waste management by landfilling, incineration or mechanical—biological waste treatment. For average European waste composition most waste management scenarios provided negative global warming factors and hence overall savings in greenhouse gas emissions: Scenarios with landfilling saved 0—400, scenarios with incineration saved 200—700, and scenarios with mechanical-biological treatment saved 200— 750 kg CO2-eq. tonne— 1 municipal waste depending on recycling scheme and energy recovery. Key parameters were the amount of paper recycled (it was assumed that wood made excessive by paper recycling substituted for fossil fuel), the crediting of the waste management system for the amount of energy recovered (hard-coal-based energy was substituted), and binding of biogenic carbon in landfills. Most other processes were of less importance. Rational waste management can provide significant savings in society’s emission of greenhouse gas depending on waste composition and efficient utilization of the energy recovered.
Municipal solid waste management scenarios for Attica and their greenhouse gas emission impact
Authors: Papageorgiou Asterios , Karagiannidis Avraam , Barton John R. , Kalogirou Efstratios
Published: October 2009

Disposal of municipal solid waste in sanitary landfills is still the main waste management method in the Attica region, as in most regions of Greece. Nevertheless, diversion from landfilling is being promoted by regional plans, in which the perspectives of new waste treatment technologies are being evaluated. The present study aimed to assess the greenhouse gas (GHG) emissions impact of different municipal solid waste treatment technologies currently under assessment in the new regional plan for Attica. These technologies are mechanical—biological treatment, mass-burn incineration and mechanical treatment and have been assessed in the context of different scenarios. The present study utilized existing methodologies and emission factors for the quantification of GHG emissions from the waste management process and found that all technologies under assessment could provide GHG emission savings. However, the performance and ranking of these technologies is strongly dependent on the existence of end markets for the waste-derived fuels produced by the mechanical—biological treatment processes. In the absence of these markets the disposal of these fuels would be necessary and thus significant GHG savings would be lost.
Reduction of Structural Acoustic Radiation Via Left and Right Eigenvector Assignment Approach
Authors: Wu T.Y. , Wang K.W.
Published: October 2009

The objective of this research is to investigate the feasibility of utilizing a new left—right eigenvector tailoring method in reducing the acoustical radiations of flexible structures. The structural sound pressure radiation can be expressed in terms of a combination of vibration modes, where its magnitude is also a function of the external disturbance distribution. In other words, the radiated sound pressure level depends on both the right eigenvectors (related to the structural mode shapes) and left eigenvectors (related to the system disturbance rejection ability) of the vibrating structure. The basic idea of the proposed approach is to simultaneously modify the structural modal velocity distribution and the system capability of disturbance rejection through active left—right eigenvector assignment control actions, so that the sound pressure radiated from the vibrating structure can be reduced. Numerical simulations are performed to evaluate the effectiveness of the proposed method on structural noise reduction. Frequency responses of sound pressure at a receiver in the selected frequency range are illustrated. It is shown that with the proposed active control method, one can re-shape the modal velocity distribution and enhance disturbance rejection, and hence can effectively minimize the structural sound pressure radiation.
Hospice Disease Types Which Indicate a Greater Need for Bereavement Counseling
Authors: Jones Brian W.
Published: October 2009

This article attempts to find a correlation between certain disease types and increased needs for bereavement services for survivors. Data were examined from those requesting increased bereavement services from a hospice provider in Kentucky, over a 2-year span. The survivors were then matched with the disease type of their loved one to see whether there was a connection between the two. Although limited in its scope and focus, the study revealed that patients surviving Alzheimer disease, lung cancer, and renal failure consistently (at least 50% of the time) required increased bereavement services after the death of their loved one. Other disease types indicated more erratic patterns for increased grief services.
Family Support Services in Pediatric Palliative Care
Authors: Knapp Caprice A. , Contro Nancy
Published: October 2009

A fundamental premise of pediatric palliative care is that support is provided not only to the ill child but to the family as well. In doing so, a number of services may be offered to family members throughout the child’s illness, at the time of death and into bereavement, such as respite, counseling, expressive therapies, and bereavement support. Support may also be needed for the child’s peers at school, church, or on sporting teams. Evidence on family supportive care in pediatric palliative care research is scarce. The majority of existing studies are undertaken with bereaved parents. Although these studies are insightful, further information is needed to understand families’ needs along the illness trajectory and to determine whether unmet needs exist.
Ballot Question Readability and Roll-Off: The Impact of Language Complexity
Authors: Reilly Shauna , Richey Sean
Published: October 2009

Ballot questions often feature obscure and legalistic language that is difficult to comprehend. Because the language of ballot questions is often unclear, the authors hypothesize that questions with lower readability will have higher roll-off because voters will not answer questions they do not understand. The authors use an objective measure of readability to code readability scores for 1,211 state-level ballot questions from 1997 to 2007. Using hierarchical linear regression models of state-level data, the authors find that increased complexity leads to more roll-off. The authors further analyze some possible influences on readability by examining whether it is affected by the question topic.
Sodium Ferulate Modified Gene Expression Profile of Oxidized Low-Density Lipoprotein-Stimulated Human Umbilical Vein Endothelial Cells
Authors: Zhang Dongxian , Bi Zhuoyue , Li Yang , Zheng Hong , Li Li , Ouyang Jingping , Wang Baohua , Bi Yongyi
Published: October 2009

Oxidized low-density lipoprotein (ox-LDL) is known to trigger vascular injury in atherosclerosis development. Sodium ferulate is an effective component from Chinese medicines with various beneficial cardiovascular pharmacological activities. Here, we investigated the effects of sodium ferulate on the gene expression profile of ox-LDL-stimulated endothelial cells. Cultured human umbilical vein endothelial cells (HUVECs) were treated with ox-LDL (50 μg/mL) in the absence or presence of sodium ferulate (5 μmol/L). Sodium ferulate significantly reduced ox-LDL-induced endothelial cell death as evaluated by cell viability assay. Human oligonucleotide microarray analysis demonstrated that a total of 32 ox-LDL-induced genes were significantly downregulated to control levels by sodium ferulate. These genes included members from families of chemokine, inflammatory factor, growth factor, and nuclear receptor. These data provided an overview of the gene expression profile of endothelial cells in response to ox-LDL and sodium ferulate, and demonstrated that sodium ferulate could regulate the expression of inflammation-related genes in endothelial cells and has the potential to benefit endothelial function in the setting of atherosclerosis.
Identification of early growth response protein 1 (EGR-1) as a novel target for JUN-induced apoptosis in multiple myeloma
Authors: Chen Lijuan , Wang Siqing , Zhou Yiming , Wu Xiaosong , Entin Igor , Epstein Joshua , Yaccoby Shmuel , Xiong Wei , Barlogie Bart , Shaughnessy John D. , Zhan Fenghuang
Published: October 2009

Tumor–bone marrow microenvironment interactions in multiple myeloma (MM) are documented to play crucial roles in plasma-cell growth/survival. In vitro coculture of MM cells with osteoclasts supported cell survival and significantly down-regulated JUN expression. JUN expression in myeloma cells from late-stage and high-risk MM was significantly lower than in plasma cells from healthy donors, monoclonal gammopathy of undetermined significance, smoldering MM, and low-risk MM; patients with low-JUN–expressing MM cells had earlier disease-related deaths. JUN overexpression in MM cells induced cell death and growth inhibition and up-regulated expression of early growth response protein 1 (EGR-1), whose low expression also carried unfavorable clinical implications. EGR-1 knockdown in MM cells abrogated JUN overexpression-induced MM cell death and growth inhibition, indicating that EGR-1 acts directly downstream of JUN. JUN modulates myeloma cell apoptosis through interacting with EGR-1, which down-regulates Survivin and triggers caspase signaling. Importantly, high JUN or EGR-1 expression was associated with improved outcome in Total Therapy 3, in which bortezomib is given throughout therapy, versus Total Therapy 2, in which bortezomib is given only at relapse. Consistently, JUN or EGR-1 knockdown in cultured MM cells enhanced their resistance to bortezomib, demonstrating the crucial role of low JUN/EGR-1 expression in MM resistance to bortezomib.
A gene expression signature of CD34+ cells to predict major cytogenetic response in chronic-phase chronic myeloid leukemia patients treated with imatinib
Authors: McWeeney Shannon K. , Pemberton Lucy C. , Loriaux Marc M. , Vartanian Kristina , Willis Stephanie G. , Yochum Gregory , Wilmot Beth , Turpaz Yaron , Pillai Raji , Druker Brian J. , Snead Jennifer L. , MacPartlin Mary , O'Brien Stephen G. , Melo Junia V. , Lange Thoralf , Harrington Christina A. , Deininger Michael W. N.
Published: October 2009

In chronic-phase chronic myeloid leukemia (CML) patients, the lack of a major cytogenetic response (< 36% Ph+ metaphases) to imatinib within 12 months indicates failure and mandates a change of therapy. To identify biomarkers predictive of imatinib failure, we performed gene expression array profiling of CD34+ cells from 2 independent cohorts of imatinib-naive chronic-phase CML patients. The learning set consisted of retrospectively selected patients with a complete cytogenetic response or more than 65% Ph+ metaphases within 12 months of imatinib therapy. Based on analysis of variance P less than .1 and fold difference 1.5 or more, we identified 885 probe sets with differential expression between responders and nonresponders, from which we extracted a 75-probe set minimal signature (classifier) that separated the 2 groups. On application to a prospectively accrued validation set, the classifier correctly predicted 88% of responders and 83% of nonresponders. Bioinformatics analysis and comparison with published studies revealed overlap of classifier genes with CML progression signatures and implicated β-catenin in their regulation, suggesting that chronic-phase CML patients destined to fail imatinib have more advanced disease than evident by morphologic criteria. Our classifier may allow directing more aggressive therapy upfront to the patients most likely to benefit while sparing good-risk patients from unnecessary toxicity.
EMMPRIN promotes angiogenesis through hypoxia-inducible factor-2α–mediated regulation of soluble VEGF isoforms and their receptor VEGFR-2
Authors: Bougatef Faten , Quemener Cathy , Kellouche Sabrina , Naïmi Benyoussef , Podgorniak Marie-Pierre , Millot Guy , Gabison Eric E. , Calvo Fabien , Dosquet Christine , Lebbé Céleste , Menashi Suzanne , Mourah Samia
Published: October 2009

Extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) is thought to promote tumor angiogenesis mostly through its protease-inducing function and more recently by its ability to increase tumor cell expression of vascular endothelial growth factor (VEGF). In this study, we present evidence that EMMPRIN can promote angiogenesis by a direct effect on endothelial cells through a paracrine regulation of the VEGF/VEGF-receptor (VEGFR) system. Using human microvascular endothelial cell line–1 endothelial cells, we show that EMMPRIN selectively increased the soluble VEGF isoforms (121 and 165), but not the matrix-bound VEGF 189 form. In addition, EMMPRIN up-regulated the expression of VEGFR-2 without an effect on VEGFR-1. This increase in VEGFR-2 was responsible for the observed EMMPRIN stimulation of the migratory and tube formation capacity of endothelial cells. EMMPRIN′s effects, which were matrix metalloproteinase and urokinase-type plasminogen activator independent, were mediated primarily through hypoxia-inducible factor-2α expression, also up-regulated by EMMPRIN. VEGFR-2 increase was also observed in vivo in a mouse model of xenograph tumors overexpressing EMMPRIN. These results suggest that in addition to increasing protease production, EMMPRIN may contribute to the formation of a reactive stroma also through the up-regulation of hypoxia-inducible factor-2α, VEGFR-2, and the soluble forms of VEGF in endothelial cells, thus directly regulating the angiogenic process.
Migrating monocytes recruited to the spleen play an important role in control of blood stage malaria
Authors: Sponaas Anne-Marit , Freitas do Rosario Ana Paula , Voisine Cecile , Mastelic Beatris , Thompson Joanne , Koernig Sandra , Jarra William , Renia Laurent , Mauduit Marjorie , Potocnik Alexandre J. , Langhorne Jean
Published: October 2009

Host responses controlling blood-stage malaria include both innate and acquired immune effector mechanisms. During Plasmodium chabaudi infection in mice, a population of CD11bhighLy6C+ monocytes are generated in bone marrow, most of which depend on the chemokine receptor CCR2 for migration from bone marrow to the spleen. In the absence of this receptor mice harbor higher parasitemias. Most importantly, splenic CD11bhighLy6C+ cells from P chabaudi–infected wild-type mice significantly reduce acute-stage parasitemia in CCR2−/− mice. The CD11bhighLy6C+ cells in this malaria infection display effector functions such as production of inducible nitric oxide synthase and reactive oxygen intermediates, and phagocytose P chabaudi parasites in vitro, and in a proportion of the cells, in vivo in the spleen, suggesting possible mechanisms of parasite killing. In contrast to monocyte-derived dendritic cells, CD11bhighLy6C+ cells isolated from malaria-infected mice express low levels of major histocompatibility complex II and have limited ability to present the P chabaudi antigen, merozoite surface protein-1, to specific T-cell receptor transgenic CD4 T cells and fail to activate these T cells. We propose that these monocytes, which are rapidly produced in the bone marrow as part of the early defense mechanism against invading pathogens, are important for controlling blood-stage malaria parasites.
How I treat age-related morbidities in elderly persons with hemophilia
Authors: Mannucci Pier M. , Schutgens Roger E. G. , Santagostino Elena , Mauser-Bunschoten Evelien P.
Published: October 2009

In persons with hemophilia, life expectancy is now approaching that of the general male population, at least in countries that can afford regular replacement therapy with coagulation factor concentrates. The new challenges for comprehensive treatment centers are thus to provide optimal health care for this aging population of patients, who often present not only with the comorbidities typically associated with hemophilia (arthropathy, chronic pain, blood-borne infections), but also with common age-related illnesses such as cardiovascular disease and cancer. There are no evidence-based guidelines for the management of these conditions, which often require drugs that interfere with hemostasis, enhance the bleeding tendency, and warrant more intensive replacement therapy. At the moment, elderly patients with hemophilia affected by other diseases should be managed like their age-group peers without hemophilia, provided replacement therapy is tailored to the heightened risk of bleeding associated with the need for invasive procedures and drugs that further compromise the deranged hemostasis. More detailed advice is provided on the schedules of replacement therapy needed to tackle cardiovascular diseases, such as acute coronary syndromes and nonvalvular atrial fibrillation, because these conditions will become more and more frequent challenges for the comprehensive treatment centers.
Costs and Benefits of the National Cancer Institute Central Institutional Review Board
Authors: Wagner Todd H. , Murray Christine , Goldberg Jacquelyn , Adler Jeanne M. , Abrams Jeffrey
Published: October 2009

Purpose

In 2001, the National Cancer Institute (NCI) formed the Central Institutional Review Board (CIRB) to conduct a single human subjects review for its multisite phase III oncology trials. The goal of this study was to assess whether NCI's CIRB was associated with lower effort, time, and cost in processing adult phase III oncology trials.

Methods

We conducted an observational study and compared sites affiliated with the NCI CIRB to unaffiliated sites that used their local IRB for review. Oncology research staff and IRB staff were surveyed to understand effort and timing. Response rates were 60% and 42%, respectively. Analysis of these survey data yielded information on effort, timing, and costs. We combined these data with CIRB operational data to determine the net savings of the CIRB using a societal perspective.

Results

CIRB affiliation was associated with faster reviews (33.9 calendar days faster on average), and 6.1 fewer hours of research staff effort. CIRB affiliation was associated with a savings of $717 per initial review. The estimated cost of running the CIRB was $161,000 per month. The CIRB yielded a net cost of approximately $55,000 per month from a societal perspective. Whether the CIRB results in higher or lower quality reviews was not assessed because there is no standard definition of review quality.

Conclusion

The CIRB was associated with decreases in investigator and IRB staff effort and faster protocol reviews, although savings would be higher if institutions used the CIRB as intended.
Ubiquitin Carboxyl-Terminal Hydrolase L3 Promotes Insulin Signaling and Adipogenesis
Authors: Suzuki Mari , Setsuie Rieko , Wada Keiji
Published: October 2009

Insulin is a potent adipogenic hormone that triggers the induction of a series of transcription factors and specific proteins governing the differentiation of preadipocytes into mature adipocytes. Here we report that ubiquitin carboxyl-terminal hydrolase (UCH)-L3, a deubiquitinating enzyme, promotes insulin signaling and adipogenesis. Uchl3−/− mice had less visceral white adipose tissue compared with wild-type mice. In vitro adipogenesis experiments revealed that mouse embryonic fibroblasts (MEFs) and preadipocytes from Uchl3−/− mice had impaired ability to differentiate into mature adipocytes than those from wild-type mice. This difference was diminished by removing insulin from the medium. RT-PCR analysis showed that insulin-regulated expression of srebp1c, fas, glut4, and adiponectin is impaired in Uchl3−/− cells. The phosphorylation of insulin/IGF-I receptor, Akt, glycogen synthase kinase-3β, and FoxO1 was decreased in Uchl3−/− MEFs treated with insulin. Moreover, ectopic expression of wild-type UCH-L3 restored the phosphorylation of insulin/IGF-I receptor and adipocyte differentiation in Uchl3−/− MEFs. In contrast, hydrolase activity-deficient UCH-L3 did not enhance insulin signaling and the expression of glut4, fabp4, and adiponectin, resulting in impaired formation of large lipid droplets. These results suggest that UCH-L3 promotes adipogenesis by enhancing insulin signaling in a hydrolase activity-dependent manner.
Mechanisms Involved in 3′,5′-Cyclic Adenosine Monophosphate-Mediated Inhibition of the Ubiquitin-Proteasome System in Skeletal Muscle
Authors: Gonçalves Dawit A. P. , Lira Eduardo C. , Baviera Amanda M. , Cao Peirang , Zanon Neusa M. , Arany Zoltan , Bedard Nathalie , Tanksale Preeti , Wing Simon S. , Lecker Stewart H. , Kettelhut Isis C. , Navegantes Luiz C. C.
Published: October 2009

Although it is well known that catecholamines inhibit skeletal muscle protein degradation, the molecular underlying mechanism remains unclear. This study was undertaken to investigate the role of β2-adrenoceptors (AR) and cAMP in regulating the ubiquitin-proteasome system (UPS) in skeletal muscle. We report that increased levels of cAMP in isolated muscles, promoted by the cAMP phosphodiesterase inhibitor isobutylmethylxanthine was accompanied by decreased activity of the UPS, levels of ubiquitin-protein conjugates, and expression of atrogin-1, a key ubiquitin-protein ligase involved in muscle atrophy. In cultured myotubes, atrogin-1 induction after dexamethasone treatment was completely prevented by isobutylmethylxanthine. Furthermore, administration of clenbuterol, a selective β2-agonist, to mice increased muscle cAMP levels and suppressed the fasting-induced expression of atrogin-1 and MuRF-1, atrogin-1 mRNA being much more responsive to clenbuterol. Moreover, clenbuterol increased the phosphorylation of muscle Akt and Foxo3a in fasted rats. Similar responses were observed in muscles exposed to dibutyryl-cAMP. The stimulatory effect of clenbuterol on cAMP and Akt was abolished in muscles from β2-AR knockout mice. The suppressive effect of β2-agonist on atrogin-1 was not mediated by PGC-1α (peroxisome proliferator-activated receptor-γ coactivator 1α known to be induced by β2-agonists and previously shown to inhibit atrogin-1 expression), because food-deprived PGC-1α knockout mice were still sensitive to clenbuterol. These findings suggest that the cAMP increase induced by stimulation of β2-AR in skeletal muscles from fasted mice is possibly the mechanism by which catecholamines suppress atrogin-1 and the UPS, this effect being mediated via phosphorylation of Akt and thus inactivation of Foxo3.