bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design
Authors: Gil L. Alejandro , Valiente Pedro A. , Pascutti Pedro G. , Pons Tirso
Published: July 2011

The development of efficient and selective antimalariais remains a challenge for the pharmaceutical industry. The aspartic proteases plasmepsins, whose inhibition leads to parasite death, are classified as targets for the design of potent drugs. Combinatorial synthesis is currently being used to generate inhibitor libraries for these enzymes, and together with computational methodologies have been demonstrated capable for the selection of lead compounds. The high structural flexibility of plasmepsins, revealed by their X-ray structures and molecular dynamics simulations, made even more complicated the prediction of putative binding modes, and therefore, the use of common computational tools, like docking and free-energy calculations. In this review, we revised the computational strategies utilized so far, for the structure-function relationship studies concerning the plasmepsin family, with special focus on the recent advances in the improvement of the linear interaction estimation (LIE) method, which is one of the most successful methodologies in the evaluation of plasmepsin-inhibitor binding affinity.
A Numerical Method for Two‐Stage Stochastic Programs under Uncertainty
Authors: Bosch Paul
Published: July 2011

Motivated by problems coming from planning and operational management in
power generation companies, this work extends the traditional two‐stage linear stochastic program by adding probabilistic constraints in the second stage. In this work we describe, under special assumptions, how the two‐stage stochastic programs with mixed probabilities can be treated computationally. We obtain a convex conservative approximations of the chance constraints defined in second stage of our model and use Monte Carlo simulation techniques for approximating the expectation function in the first stage by the average. This approach raises with another question: how to solve the linear program with the convex conservative approximation (nonlinear constrains) for each scenario?
The Western Amazonian Boundary for Avifauna Determined by Species Distribution Patterns and Geographical and Ecological Features
Authors: Nores Manuel
Published: July 2011

In northern South America, an extensive tropical lowland runs 5,000 km from the Atlantic coast to the foot of the Andes. The slope is gentle until about 500 m where the eastern Andes rise abruptly. The lowland supports Amazonia, which is the most extensive tract of tropical rainforest on the planet. Most of its boundaries are well defined, but the boundary between Amazonia and the forest of the eastern slopes of the Andes has not been clearly defined. To determine for avifauna whether Amazonia is restricted to the lowland of northern South America or whether it also extends up into the eastern slopes of the Andes, different types of data were used. The results indicate that Amazonia may be restricted to the lowland that extends from the Atlantic coast to the foot of the Andes, up to about 500 m. Consequently, the number of bird species strictly endemic to Amazonia would be 290. Comparison with the distribution of vegetation on the eastern slopes of the Andes also suggests that Amazonia as a biome may be restricted to the lowland that extends from the Atlantic coast to the foot of the Andes, up to about 500 m.
Myeloid Suppressor Cells Regulate the Lung Environment—Letter
Authors: Bosiljcic Momir , Hamilton Melisa J. , Banath Judit P. , LePard Nancy E. , McDougal Denise C. , Jia Jessica X. , Krystal Gerald , Bennewith Kevin L.
Published: July 2011

4T1 murine mammary carcinoma cells implanted in syngeneic Balb/c mice are increasingly being used in metastasis research, with some groups using this model to study tumor-induced accumulation of bone marrow–derived cells in metastatic target organs. Bone marrow–derived cells (including CD11b+Gr-1+ myelomonocytic cells) are thought to modify the local lung microenvironment to facilitate subsequent colonization by metastatic tumor cells. While quantification of metastatic 4T1 tumor cells in various tissues can be done using ex vivo colony-forming assays, detection of metastatic 4T1 cells is often facilitated by expressing fluorescent proteins in the tumor cells prior to implantation. We found that Balb/c mice mount a potent immune response against 4T1 cells expressing green fluorescent protein (GFP) that includes the generation of anti-GFP antibodies in the circulation. Importantly, the number of bone marrow–derived CD11b+Gr-1+ cells and metastatic tumor cells that accumulate in the lungs is significantly decreased in mice implanted with 4T1 cells expressing GFP compared with mice bearing wild-type 4T1 tumors. Taken together, our data caution against the use of GFP-expressing tumor cells in the Balb/c mouse strain, particularly for studying the influence of immunomodulatory cells on tumor cell metastasis. Cancer Res; 71(14); 5050–1. ©2011 AACR.
IL-18 Induces PD-1–Dependent Immunosuppression in Cancer
Authors: Terme Magali , Ullrich Evelyn , Aymeric Laetitia , Meinhardt Kathrin , Desbois Mélanie , Delahaye Nicolas , Viaud Sophie , Ryffel Bernard , Yagita Hideo , Kaplanski Gilles , Prévost-Blondel Armelle , Kato Masashi , Schultze Joachim L. , Tartour Eric , Kroemer Guido , Chaput Nathalie , Zitvogel Laurence
Published: July 2011

Immunosuppressive cytokines subvert innate and adaptive immune responses during cancer progression. The inflammatory cytokine interleukin-18 (IL-18) is known to accumulate in cancer patients, but its pathophysiological role remains unclear. In this study, we show that low levels of circulating IL-18, either exogenous or tumor derived, act to suppress the NK cell arm of tumor immunosurveillance. IL-18 produced by tumor cells promotes the development of NK-controlled metastases in a PD-1–dependent manner. Accordingly, PD-1 is expressed by activated mature NK cells in lymphoid organs of tumor bearers and is upregulated by IL-18. RNAi-mediated knockdown of IL-18 in tumors, or its systemic depletion by IL-18–binding protein, are sufficient to stimulate NK cell-dependent immunosurveillance in various tumor models. Together, these results define IL-18 as an immunosuppressive cytokine in cancer. Our findings suggest novel clinical implementations of anti-PD-1 antibodies in human malignancies that produce IL-18. Cancer Res; 71(16); 5393–9. ©2011 AACR.
Epitaph of Smikros
Authors: Azarnert Leonid V.
Published: July 2011

This note contributes to the analysis of the epitaph of Smikros (CIRB 118) that originates from Kertch or its nearest vicinity. It suggests a new reconstruction for the last fourth verse of the epitaph.
>“Virtue Makes the Goal Right”: Virtue and Phronesis in Aristotle’s Ethics
Authors: Moss Jessica
Published: July 2011

Aristotle repeatedly claims that character-virtue “makes the goal right”, while Phronesis is responsible for working out how to achieve the goal. Many argue that these claims are misleading: it must be intellect that tells us what ends to pursue. I argue that Aristotle means just what he seems to say: despite putative textual evidence to the contrary, virtue is (a) a wholly non-intellectual state, and (b) responsible for literally supplying the contents of our goals. Furthermore, there are no good textual or philosophical reasons to reject this straightforward interpretation. Contrary to widespread opinion, Aristotle does not characterize Phronesis as supplying ends. Instead, its ethical import lies wholly in its ability to “determine the mean”. Moreover, because character involves non-rational cognition of the end as good, Aristotle can restrict practical intellect to deliberation without abandoning his anti-Humean view that we desire our ends because we find them good.
Saviour-Sibling and the Psychological, Ethical and Judicial Issues that It Creates: Should English and French Legislators Close the Pandora’s Box?
Authors: Madanamoothoo Allane
Published: July 2011

Since the advent of test-tube babies, advances in the biomedical field have risen steadily. In parallel, the scientific body has never since ceased to debate the ethical issues that they arise. This is particularly the case regarding saviour-sibling. Saviour-sibling refers to a child who is conceived to cure an older brother or sister suffering from a serious family genetic disease. Therefore, it is meant to give birth to a child who will provide stem-cells taken from the umbilical cord or bone marrow afterwards, to treat an elder sick sibling. In England, this practice has been explicitly allowed by the new Human Fertilisation and Embryology Act 2008 under some strict conditions. In France, this practice, authorized by the Bioethics Law of August 2004 and confirmed by its decree of implementation published in the Official Journal on 23 December 2006, is also strictly regulated. This technique opens up new perspectives and enormous hope. Its legalisation is certainly justified by the suffering of the parents and to avoid that they travel to other States where it is permitted. However, it raises serious psychological ethical and judicial issues. Following an analysis of the English and French laws on saviour siblings, its controversial side will be highlighted, before concluding whether or not this new Pandora’s box which is saviour-sibling, should be closed and other alternative methods encouraged.
Printing the Samgang haengsil-to (Illustrated Guide to the Three Relationships), a Premodern Korean Moral Primer*
Authors: Kyun Oh Young
Published: July 2011

The Samgang haengsil-to is a collection of Chinese and Korean stories of exemplary conduct performed by filial sons, loyal subjects and devoted women, which epitomize Confucian virtue entailed in the three fundamental human relations. These stories were first written in classical Chinese, accompanied by illustrations, and later appeared with vernacular Korean texts added. Ever since it was published by the court in 1434, the Samgang haengsil-to underwent numerous editorial changes during the first half of Chosn dynasty (1392-1910) with respect to the selection of stories, the content, the language, and even the appearance of the book. These changes were not made at random, nor are they addressing mere practical reasons such as facilitating reading or enhancing the book’s aesthetic appeal. Rather, there was a certain political and cultural context at work behind these changes, which reflected the shifting value system and the process of Confucianization of Chosn Korea. By tracing the major changes made to different editions of the Samgang haengsil-to, this paper discusses the influences that social and political environments exert on a text.
UK student alcohol consumption: A cluster analysis of drinking behaviour typologies
Authors: Craigs Cheryl L , Bewick Bridgette M , Gill Jan , O’May Fiona , Radley Duncan
Published: July 2011

Objective: To assess the extent to which university students are following UK Government advice regarding appropriate consumption of alcohol, and to investigate if students can be placed into distinct clusters based on their drinking behaviour.

Design: A descriptive questionnaire study.

Setting: One hundred and nineteen undergraduate students from Leeds Metropolitan University, UK.

Method: An online survey, which included a diary to record daily alcohol consumption over the previous week, was completed during the winter of 2007/08. Cluster analysis was used to classify students into subgroups based on comparable alcohol-drinking characteristics. National recommended sensible drinking behaviour guidelines in terms of total weekly alcohol intake, maximum daily alcohol intake, number of alcohol-free days and estimated blood alcohol levels were used to compare drinking behaviour the previous week by age, sex and cluster group.

Results: Consuming weekly alcohol levels considered hazardous was common (58%) with nearly 70% of responders binge drinking at least once over that period; most students (80%) were, however, following the government’s recommendation for two consecutive alcohol-free days per week. No significant differences in drinking behaviour by sex were found, but binge drinkers tended to be younger. Four distinct alcohol-drinking behaviour clusters were identified based on alcohol consumption frequency and quantity. Only students in the non or light drinkers group all remained within national recommended guidelines for weekly intake and alcohol-free days.

Conclusion: Students who consume alcohol are commonly drinking daily and weekly alcohol levels in excess of national sensible drinking guidelines; most students, however, abstain from alcohol on at least two consecutive days. The four distinct drinking clusters suggest that students would benefit from targeted interventions. In particular, personalization of interventions to reflect the distinct patterns of drinking behaviour could increase intervention effectiveness.
Factors associated with frequent psychiatric admissions in a general hospital in Spain
Authors: Martínez-Ortega José M. , Gutiérrez-Rojas Luis , Jurado Dolores , Higueras Antonio , Diaz Francisco J. , Gurpegui Manuel
Published: July 2011

Objectives:

To identify demographic or clinical factors associated with frequent admissions in a sample of patients admitted to an acute psychiatric hospitalization unit, controlling for potentially confounding factors.

Methods:

Socio-demographic variables, diagnosis, and the legal status, date and length of admission were collected for 1,722 consecutively admitted psychiatric patients during a period of up to eight years (1998–2005). Frequently admitted patients were defined as undergoing one or more admissions per year on average.

Results:

After controlling for potential confounding factors, logistic regression showed that being a frequently admitted patient was significantly associated with diagnoses of schizoaffective disorder, personality disorder or schizophrenia; an involuntary commitment at first admission; and younger age.

Conclusions:

Factors associated with frequently admitted patients should be identified in order to establish more effective strategies for preventing relapse.
The Political Economy of Maize Production and Poverty Reduction in Zambia: Analysis of the Last 50 Years
Authors: Hanjra Munir A , Culas Richard J
Published: July 2011

Poverty and food security are endemic issues in much of sub-Saharan Africa. To eradicate extreme poverty and hunger in the region remains a key Millennium Development Goal. Many African governments have pursued economic reforms and agricultural policy interventions in order to accelerate economic growth that reduces poverty faster. Agricultural policy regimes in Zambia in the last 50 years (1964–2008) are examined here to better understand their likely impact on food security and poverty, with an emphasis on the political economy of maize subsidy policies. The empirical work draws on secondary sources and an evaluation of farm household data from three villages in the Kasama District of Zambia from 1986/87 and 1992/93 to estimate a two-period econometric model to examine the impact on household welfare in a pre- and post-reform period. The analysis shows that past interventions had mixed effects on enhancing the production of food crops such as maize. While such reforms were politically popular, it did not necessarily translate into household-level productivity or welfare gains in the short term. The political economy of reforms needs to respond to the inherent diversity among the poor rural and urban households. The potential of agriculture to generate a more pro-poor growth process depends on the creation of new market opportunities that most benefit the rural poor. The state should encourage private sector investments for addressing infrastructure constraints to improve market access and accelerate more pro-poor growth through renewed investments in agriculture, rural infrastructure, gender inclusion, smarter subsidies and regional food trade. However, the financing of such investments poses significant challenges. There is a need to address impediments to the effective participation of public private investors to generate more effective poverty reduction and hunger eradication programmes. This article also explores the opportunities for new public–private investments through South–South cooperation and Asia-driven growth for reducing poverty in Zambia.
Analysis of premalignant pancreatic cancer mass spectrometry data for biomarker selection using a group search optimizer
Authors: He S , Cooper H J , Ward D G , Yao X , Heath J K
Published: July 2011

This paper presents a novel group search optimizer (GSO)-based biomarker discovery method for pancreatic cancer diagnosis using mass spectrometry (MS) data. The GSO was inspired by animal social searching behaviour. It has been shown that the global search performance of the GSO is competitive to other biologically inspired optimization algorithms. In this study, we applied a GSO as a feature selection method to MS data analysis for premalignant pancreatic cancer biomarker discovery. We first applied a smooth non-linear energy operator to detect peaks. Then a GSO with linear discriminant analysis was used to select a parsimonious set of peak windows (biomarkers) that can distinguish cancer. After selecting a set of biomarkers, a support vector machine was then applied to build a classifier to diagnosis premalignant cancer cases. We compared the GSO algorithm with a genetic algorithm, evolution strategies, evolutionary programming and a particle swarm optimizer. The results showed that the GSO-based feature selection algorithm is capable of selecting a parsimonious set of biomarkers to achieve better classification performance than other algorithms. The source code of the proposed GSO-based feature selection algorithm is available at www.cs.bham.ac.uk/~szh .
Using analytic network process and turbo particle swarm optimization algorithm for non-balanced supply chain planning considering supplier relationship management
Authors: Che ZH , Chiang Tzu-An , Che Zhen-Guo
Published: July 2011

Supply chain planning has been regarded as a key strategic decision-making activity for the enterprises under the current business circumstances. From the point of supply chain planning, the important issues are to find suitable and quality partners and to decide upon an appropriate production–distribution plan. In this study, hence, we address to develop a decision methodology for supply chain planning in multi-echelon non-balanced supply chain system, taking into account such four criteria as cost, quality, delivery and supplier relationship management and considering quantity discount and capacity constraints. The proposed methodology is based on the analytic network process and turbo particle swarm optimization (TPSO), to evaluate partners and to determine an optimal supply chain network pattern and production–distribution mode. Finally, to demonstrate the performance of the proposed TPSO algorithm, comparative numerical experiments are performed by TPSO, particle swarm optimization (PSO) and genetic algorithm (GA). Empirical analysis results demonstrate that TPSO can outperform PSO and GA in non-balanced supply chain planning problems.
Knowing Your Own Mate Value
Authors: Back Mitja D. , Penke Lars , Schmukle Stefan C. , Asendorpf Jens B.
Published: July 2011

Knowing one’s mate value (mate-value accuracy) is an important element in reproductive success. We investigated within- and between-sex differences in this ability in a real-life speed-dating event. A total of 190 men and 192 women filled out a personality questionnaire and participated in speed-dating sessions. Immediately after each date, participants recorded who they would choose as mates and who they expected would choose them. In line with evolutionarily informed hypotheses, results indicated that sociosexually unrestricted men and more agreeable women showed greater mate-value accuracy than sociosexually restricted men and less agreeable women, respectively. These results have important implications for understanding mating behavior and perhaps the origin of sex differences in personality.
Social Workers’ Role in the Canadian Mental Health Care System
Authors: Towns Ashley M. , Schwartz Karen
Published: July 2011

Objective: Using Canadian survey data this research provides social workers in Canada with a better understanding of their role in the Canadian mental health care system. Methods: By analyzing data from the Canadian Community Health Survey, Cycle 1.2 Mental Health and Well-being, the role of social workers in the Canadian mental health system was determined. Results: Findings indicated that social workers were accessed third most frequently for mental health care. While a variety of individuals accessed care from social workers, those of different sexes, ages, education, and income levels did so at significantly different rates. Conclusion: Social workers should adjust services to include those less likely to access care who may benefit from it, while maintaining services for current clients.
Adenosine and Opioid Receptors Do Not Trigger the Cardioprotective Effect of Mild Hypothermia
Authors: Darbera Lys , Chenoune Mourad , Lidouren Fanny , Ghaleh Bijan , Cohen Michael V. , Downey James M. , Berdeaux Alain , Tissier Renaud
Published: July 2011

Mild hypothermia (32°C-34°C) exerts a potent cardioprotection in animal models of myocardial infarction. Recently, it has been proposed that this beneficial effect is related to survival signaling. We, therefore, hypothesized that the well-known cardioprotective pathways dependent on adenosine and/or opioid receptors could be the trigger of hypothermia-induced salvage. Open-chest rabbits were accordingly exposed to 30 minutes of coronary artery occlusion (CAO) under normothermic (NT) or hypothermic ([HT] 32°C) conditions. In the latter, hypothermia was induced by total liquid ventilation with temperature-controlled perfluorocarbons in order to effect ultrafast cooling and to accurately control cardiac temperature. After 4 hours of reperfusion, infarct and no-reflow zone sizes were assessed and quantified as a percentage of the risk zone. In animals experiencing HT ischemia, the infarct size was dramatically reduced as compared to NT animals (9% ± 3% vs 55% ± 2% of the risk zone, respectively). Importantly, administration of opioid and adenosine receptor antagonists (naloxone [6 mg/kg iv] and 8-( p-sulfophenyl) theophylline [20 mg/kg iv], respectively) did not alter the infarct size or affect the cardioprotective effect of hypothermia. Doses of these 2 antagonists were appropriately chosen since they blunted infarct size reduction induced by selective opioid or adenosine receptor stimulation with morphine (0.3 mg/kg iv) or N6-cyclopentyladenosine ([CPA] 100 μg/kg iv), respectively. Therefore, the cardioprotective effect of mild hypothermia is not triggered by either opioid or adenosine receptor activation, suggesting the involvement of other cardioprotective pathways.
A stable self-tuning proportional-integral-derivative controller for a class of multi-input multi-output nonlinear systems
Authors: Boubakir Ahsene , Labiod Salim , Boudjema Fares
Published: July 2011

This paper proposes a self-tuned proportional-integral-derivative (PID) controller for a class of uncertain continuous-time multi-input multi-output nonlinear dynamic systems. Within this scheme, the PID controller is employed to approximate an unknown ideal controller that can achieve control objectives. The three PID control gains are adjustable parameters and they are updated online with a stable adaptation mechanism designed to minimize the error between the unknown ideal controller and the used PID controller. The proposed approach can be regarded as a simple and effective model-free control because the mathematical model of the system is assumed unknown. The stability analysis of the closed-loop system is performed using a Lyapunov approach. It is proved that all signals in the closed-loop system are uniformly ultimately bounded and that the tracking error can be made to converge to zero in the absence of approximation errors. The effectiveness of the proposed adaptive PID control is demonstrated in simulation.
Modeling and optimization of floating raft systems in submarines under different objectives by using hybrid genetic algorithm
Authors: Xiuchang Huang , Shiyin Xu , Aihua Jiang , Hongxing Hua
Published: July 2011

A systematic modeling and optimization method for analyzing typical floating raft systems in submarines is presented and optimization under different vibro-acoustic objectives is investigated. The Frequency Response Function-based (FRF-based) substructuring method and the coupled Finite Element/Boundary Element (FE/BE) method are employed to study vibration transmission from the vibrating machinery to the base structure as well as the vibro-acoustic behavior of the fluid- loaded cylindrical structure. The hybrid genetic algorithm (HGA) involving the FRF-based substructuring sensitivity analysis (SA) and the genetic algorithm (GA) is developed and applied to obtain the optimal values of stiffness of isolators under five objective functions at low frequencies. Optimization is carried out for two cases where the fluid–structure interaction is considered and neglected respectively. The modeling results demonstrate that the effect of fluid-loading reduces the driving point mobility of the connecting points on the base structure but has little influence on the isolation frequencies of the whole floating raft system. The optimized results are compared with those obtained by SA and GA. The results of SA show a regular trend of variation while those of GA show an irregular trend. Since GA is a stochastic optimization technique, the trend of variation in the results of HGA combines those of GA and SA. The optimized results demonstrate that HGA possesses the merits of SA and GA, and never gets trapped at a local optimum or goes into premature convergence. Compared with SA and GA, however, it requires more evaluation of objective functions in each iteration step and as a result is not computationally efficient.
A two-stage method for damage detection using frequency responses and statistical theory
Authors: Guo Hui Yong , Li Zheng Liang
Published: July 2011

In order to precisely identify the location and extent of structural damage, a two-stage damage detection method using frequency responses and statistical theory is presented in this paper. First, a damage index, which comes from the product of the stiffness changes and measured responses, is proposed. We can utilize degree-of-freedom (d.f.) damage index to localize the damage locations. Then, in order to calculate the extent of damage, a damage quantification formula is deduced from a reduced degree-of-freedom system. Finally, the effect of measurement noise is taken into account in the identification process and the measurement noise sensitivity formula based on statistical theory is presented. The numerical example and analysis demonstrate the excellent performance of the proposed two-stage method to identify damage locations and extent compared with other methods, such as the directness generalized inverse method.
Dynamic strain measurements of a cantilever using the improved bonding fiber Bragg grating
Authors: Hwang Gwo-Shyang , Ma Chien-Ching , Huang Ding-Wei
Published: July 2011

For a surface mounted fiber Bragg grating (FBG) strain sensor, this study used an improved bonding method that distributes cement only on the two ends of the grating and leaves the grating free from cement. According to a recent numerical study, for a conventional surface mounted FBG strain sensor its relationship between average strains (within its glued grating) and voltage signals is nonlinear and changeable depending on the variation patterns of strain gradients (within its glued grating) in a strain history. By contrast, the relationship for the improved bonding one is linear because of the constant zero strain gradient within the glue-free grating. To experimentally verify the linear relationship for the improved bonding fiber Bragg grating (IBFBG), this study set up a cantilever with both the IBFBG and a resistance strain gauge surface mounted in close proximity, and the vibration responses were induced by impactions of a free-falling steel ball on the cantilever's surface. Experimental results indicate that dynamic calibrations of an IBFBG by using a commonly used resistance strain gauge are possible because both sensors in close proximity have their changes of voltage signals almost proportional to each other.
Optimization of the current flowing technique aimed at semi-passive multi-modal vibration reduction
Authors: Cigada A , Manzoni S , Redaelli M , Vanali M
Published: July 2011

The paper deals with the analysis and optimization of a semi-passive multi-modal vibration attenuation technique exploiting piezo-benders actuators. Although there are different methods available in the literature, attention has been focused on the current flowing technique as it has a number of advantages with respect to the other approaches. In this context the control bender is linked to an electrical impedance, designed to maximize the mechanical energy dissipation. Though the method has already been presented in the literature, many points have still to be investigated. The paper gives a deeper analysis of this control technique and then presents an algorithm aimed at optimizing the electrical network linked to the bender.
The ‘Long Winding Road’ to Adulthood
Authors: Peterson Abby
Published: July 2011

This article follows up the life stories of 15 young people from a previous study, all who grew up in a neighbourhood we called Clover Valley. Researchers have emphasized the risks encountered by young people growing up in depressed neighbourhoods such as Clover Valley. Most of the young people in our study have managed to more or less successfully negotiate different paths towards adulthood and for others (particularly among the boys) the paths have been more arduous. By analyzing more closely the life stories of three of the interviewees, I investigate how young adults actively construct and reconstruct their life stories in a way that has helped them make sense of the to and fro of life and how they have tried to influence the outcomes of their choices. In particular, attention is directed as to the ways Clover Valley has inscribed their life stories and how their experiences of growing up in Clover Valley has influenced the life courses they have taken. In focus is the resiliency of young people who overcome the odds against successful paths to adulthood and social inclusion. Central for an understanding of the long winding road to adulthood sketched in the life history narratives was the way in which their growing up in Clover Valley inscribed their different ‘possible selves’, especially their fear for possible selves.
Democracy and punishment: A radical view
Authors: Rowan Mike
Published: July 2011

This article begins by arguing against the claim of some scholars that the opinions and attitudes of ordinary citizens about criminal justice policy are bounded either by feelings of hostility toward criminal offenders or by indifference toward their rights as human beings. The purpose of this discussion will be to demonstrate that there is sufficient cause to think that meaningful democratic engagement on criminal justice issues is possible, such that an inquiry into the democratic legitimacy of criminal justice policy is worth taking up. This discussion sets the stage for an inquiry into the conditions of democratic legitimacy. The article critiques the view that institutionalized deliberation is a sufficient condition for regarding criminal justice policies as legitimate and argues instead for a radical-democratic approach to evaluating the democratic legitimacy of criminal justice policies.
Down-regulation of the RUNX1-target gene NR4A3 contributes to hematopoiesis deregulation in familial platelet disorder/acute myelogenous leukemia
Authors: Bluteau Dominique , Gilles Laure , Hilpert Morgane , Antony-Debré Iléana , James Chloe , Debili Najet , Camara-Clayette Valerie , Wagner-Ballon Orianne , Cordette-Lagarde Veronique , Robert Thomas , Ripoche Hugues , Gonin Patrick , Swierczek Sabina , Prchal Josef , Vainchenker William , Favier Remi , Raslova Hana
Published: July 2011

RUNX1 encodes a DNA-binding α subunit of the core-binding factor, a heterodimeric transcription factor. RUNX1 is a master regulatory gene in hematopoiesis and its disruption is one of the most common aberrations in acute leukemia. Inactivating or dominant-negative mutations in the RUNX1 gene have been also identified in pedigrees of familial platelet disorders with a variable propensity to develop acute myeloid leukemia (FPD/AML). We performed analysis of hematopoiesis from 2 FPD/AML pedigrees with 2 distinct RUNX1 germline mutations, that is, the R139X in a pedigree without AML and the R174Q mutation in a pedigree with AML. Both mutations induced a marked increase in the clonogenic potential of immature CD34+CD38− progenitors, with some self-renewal capacities observed only for R174Q mutation. This increased proliferation correlated with reduction in the expression of NR4A3, a gene previously implicated in leukemia development. We demonstrated that NR4A3 was a direct target of RUNX1 and that restoration of NR4A3 expression partially reduced the clonogenic potential of patient progenitors. We propose that the down-regulation of NR4A3 in RUNX1-mutated hematopoietic progenitors leads to an increase in the pool of cells susceptible to be hit by secondary leukemic genetic events.
Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia
Authors: Badoux Xavier C. , Keating Michael J. , Wen Sijin , Lee Bang-Ning , Sivina Mariela , Reuben James , Wierda William G. , O'Brien Susan M. , Faderl Stefan , Kornblau Steven M. , Burger Jan A. , Ferrajoli Alessandra
Published: July 2011

The best initial therapy for elderly patients with chronic lymphocytic leukemia (CLL) has not yet been defined. We investigated the activity of lenalidomide as initial therapy for elderly patients with CLL. Sixty patients with CLL 65 years of age and older received treatment with lenalidomide orally 5 mg daily for 56 days, then titrated up to 25 mg/d as tolerated. Treatment was continued until disease progression. At a median follow-up of 29 months, 53 patients (88%) are alive and 32 patients (53%) remain on therapy. Estimated 2-year progression-free survival is 60%. The overall response rate to lenalidomide therapy is 65%, including 10% complete response, 5% complete response with residual cytopenia, 7% nodular partial response, and 43% partial response. Neutropenia is the most common grade 3 or 4 treatment-related toxicity observed in 34% of treatment cycles. Major infections or neutropenic fever occurred in 13% of patients. Compared with baseline levels, we noted an increase in serum immunoglobulin levels across all classes, and a reduction in CCL3 and CCL4 plasma levels was noted in responding patients. Lenalidomide therapy was well tolerated and induced durable remissions in this population of elderly, symptomatic patients with CLL. This study was registered at www.clinicaltrials.gov as #NCT00535873.
Construction of a computable cell proliferation network focused on non-diseased lung cells
Authors: Westra Jurjen W , Schlage Walter K , Frushour Brian P , Gebel Stephan , Catlett Natalie L , Han Wanjiang , Eddy Sean F , Hengstermann Arnd , Matthews Andrea L , Mathis Carole , Lichtner Rosemarie B , Poussin Carine , Talikka Marja , Veljkovic Emilija , Van Hooser Aaron A , Wong Benjamin , Maria Michael J , Peitsch Manuel C , Deehan Renee , Hoeng Julia
Published: July 2011

Background

Critical to advancing the systems-level evaluation of complex biological processes is the development of comprehensive networks and computational methods to apply to the analysis of systems biology data (transcriptomics, proteomics/phosphoproteomics, metabolomics, etc.). Ideally, these networks will be specifically designed to capture the normal, non-diseased biology of the tissue or cell types under investigation, and can be used with experimentally generated systems biology data to assess the biological impact of perturbations like xenobiotics and other cellular stresses. Lung cell proliferation is a key biological process to capture in such a network model, given the pivotal role that proliferation plays in lung diseases including cancer, chronic obstructive pulmonary disease (COPD), and fibrosis. Unfortunately, no such network has been available prior to this work.

Results

To further a systems-level assessment of the biological impact of perturbations on non-diseased mammalian lung cells, we constructed a lung-focused network for cell proliferation. The network encompasses diverse biological areas that lead to the regulation of normal lung cell proliferation (Cell Cycle, Growth Factors, Cell Interaction, Intra- and Extracellular Signaling, and Epigenetics), and contains a total of 848 nodes (biological entities) and 1597 edges (relationships between biological entities). The network was verified using four published gene expression profiling data sets associated with measured cell proliferation endpoints in lung and lung-related cell types. Predicted changes in the activity of core machinery involved in cell cycle regulation (RB1, CDKN1A, and MYC/MYCN) are statistically supported across multiple data sets, underscoring the general applicability of this approach for a network-wide biological impact assessment using systems biology data.

Conclusions

To the best of our knowledge, this lung-focused Cell Proliferation Network provides the most comprehensive connectivity map in existence of the molecular mechanisms regulating cell proliferation in the lung. The network is based on fully referenced causal relationships obtained from extensive evaluation of the literature. The computable structure of the network enables its application to the qualitative and quantitative evaluation of cell proliferation using systems biology data sets. The network is available for public use.
A simple and efficient tool for trapping gravid Anopheles at breeding sites
Authors: Harris Caroline , Kihonda Japhet , Lwetoijera Dickson , Dongus Stefan , Devine Gregor , Majambere Silas
Published: July 2011

Background

No effective tool currently exists for trapping ovipositing malaria vectors. This creates a gap in our ability to investigate the behavior and ecology of gravid Anopheles.

Findings

Here we describe a simple trap that collects ovipositing Anopheline and Culicine mosquitoes. It consists of an acetate sheet coated in glue that floats on the water surface. Ten breeding sites were selected in rural Tanzania and 10 sticky traps set in each. These caught a total of 74 gravid Anopheles (54 An. arabiensis, 1 An. gambiae s.s. and 16 unamplified) and 1333 gravid Culicines, in just two trap nights. This simple sampling tool provides an opportunity to further our understanding of the behavior and ecology of gravid female Anophelines. It strongly implies that at least two of the major vectors of malaria in Africa land on the water surface during the oviposition process, and demonstrates that Anophelines and Culicines often share the same breeding sites.

Conclusion

This simple and efficient trap has clear potential for the study of oviposition site choice and productivity, gravid dispersal, and vector control techniques which use oviposition behavior as a means of disseminating larvicides.
Development of tolerogenic dendritic cells and regulatory T cells favors exponential bacterial growth and survival during early respiratory tularemia
Authors: Periasamy Sivakumar , Singh Anju , Sahay Bikash , Rahman Tabassum , Feustel Paul J , Pham Giang H , Gosselin Edmund J , Sellati Timothy J
Published: July 2011

Tularemia is a vector-borne zoonosis caused by Ft, a Gram-negative, facultative intracellular bacterium. Ft exists in two clinically relevant forms, the European biovar B (holarctica), which produces acute, although mild, self-limiting infections, and the more virulent United States biovar A (tularensis), which is often associated with pneumonic tularemia and more severe disease. In a mouse model of tularemia, respiratory infection with the virulence-attenuated Type B (LVS) or highly virulent Type A (SchuS4) strain engenders peribronchiolar and perivascular inflammation. Paradoxically, despite an intense neutrophilic infiltrate and high bacterial burden, Th1-type proinflammatory cytokines (e.g., TNF, IL-1β, IL-6, and IL-12) are absent within the first ∼72 h of pulmonary infection. It has been suggested that the bacterium has the capacity to actively suppress or block NF-κB signaling, thus causing an initial delay in up-regulation of inflammatory mediators. However, our previously published findings and those presented herein contradict this paradigm and instead, strongly support an alternative hypothesis. Rather than blocking NF-κB, Ft actually triggers TLR2-dependent NF-κB signaling, resulting in the development and activation of tDCs and the release of anti-inflammatory cytokines (e.g., IL-10 and TGF-β). In turn, these cytokines stimulate development and proliferation of Tregs that may restrain Th1-type proinflammatory cytokine release early during tularemic infection. The highly regulated and overall anti-inflammatory milieu established in the lung is permissive for unfettered growth and survival of Ft. The capacity of Ft to evoke such a response represents an important immune-evasive strategy.
Direct Decomposition of NO into N2 and O2 on C-type Cubic Y2O3–ZrO2 and Y2O3–ZrO2–BaO
Authors: Tsujimoto Soichiro , Wang Xiaojing , Masui Toshiyuki , Imanaka Nobuhito
Published: July 2011

Catalytic activities for direct NO decomposition were investigated on C-type cubic Y2O3–ZrO2 and Y2O3–ZrO2–BaO prepared by coprecipitation. Introduction of excess oxide anions in the Y2O3 lattice was achieved by partial substitution of the Y3+ sites with Zr4+, and high NO decomposition activity was obtained for the (Y0.97Zr0.03)2O3.03 catalyst. In addition, the catalytic activity was further enhanced by partial substitution of the Y3+ sites in the Y2O3–ZrO2 solid solution with Ba2+, and the (Y0.89Zr0.07Ba0.04)2O3.03 catalyst exhibited the highest NO decomposition activity among the samples prepared; NO conversion to N2 reached 90% at 1173 K in the absence of O2 (NO/He atmosphere), and a relatively high conversion ratio was observed even in the presence of O2, H2O, or CO2, compared with the activities of conventional direct NO decomposition catalysts. These results indicate that the C-type cubic Y2O3–ZrO2–BaO catalyst is a new potential candidate for direct NO decomposition.
Core surgical training and progression into specialty surgical training: how do we get the balance right?
Authors: Carr Alison S , Munsch Chris , Buggle Steve , Hamilton Patricia
Published: July 2011

Doctors training in surgery in England usually complete a two-year core surgical training programme (CT1 and CT2) and then apply for entry into a surgical specialty training programme at ST3. This is a highly competitive process. Currently, ST3 is the only level of entry into specialty training and all doctors wishing to obtain a Certificate of Completion of Training (CCT) in a surgical specialty must apply for ST3 posts, irrespective of their previous surgical experience. Consequently, doctors who apply for ST3 entry directly from core surgical training find themselves competing against doctors with considerably more surgical experience.
Oral cancer – why do politicians ignore it?
Authors: Mitchell David A
Published: July 2011

The Faculty of Dental Surgery is one of many groups represented on the Cancer Services Committee (CCS) of the RCS and it is in this capacity that I have become increasingly concerned about the lack of awareness of a disease that is 75% preventable and, if treated early, 80% curable, among those who influence the care of patients with cancer in the UK.
Learning to lead in primary dental care
Authors: Worker Charlotte
Published: July 2011

Evolving healthcare systems place new pressures on those charged with delivering care, as the system strives for improvements in effectiveness and efficiency. Strong leadership and management is necessary so that the rationale for change and methods to implement any changes can be evaluated appropriately. Leaders and managers themselves must be conversant with the relevant issues and be able to articulate how a given system needs to adapt to ensure the delivery of required outcomes without compromising quality.
Outcomes: the Battle for Hearts and Minds
Authors: Bridgewater Ben
Published: July 2011

The cardiac surgical community in the UK has been at the forefront of collecting, analysing and publishing clinical outcomes. The outcome we have focused on is post-operative, risk-adjusted, in-hospital mortality, and comparative results for hospitals and the majority of surgeons have been published through the Care Quality Commission website since 2005.
Compensated pathogenic deviations
Authors: Barešić Anja , Martin Andrew C.R.
Published: July 2011

Deleterious or ‘disease-associated’ mutations are mutations that lead to disease with high phenotype penetrance: they are inherited in a simple Mendelian manner, or, in the case of cancer, accumulate in somatic cells leading directly to disease. However, in some cases, the amino acid that is substituted resulting in disease is the wild-type native residue in the functionally equivalent protein in another species. Such examples are known as ‘compensated pathogenic deviations’ (CPDs) because, somewhere in the second species, there must be compensatory mutations that allow the protein to function normally despite having a residue which would cause disease in the first species. Depending on the nature of the mutations, compensation can occur in the same protein, or in a different protein with which it interacts. In principle, compensation can be achieved by a single mutation (most probably structurally close to the CPD), or by the cumulative effect of several mutations. Although it is clear that these effects occur in proteins, compensatory mutations are also important in RNA potentially having an impact on disease. As a much simpler molecule, RNA provides an interesting model for understanding mechanisms of compensatory effects, both by looking at naturally occurring RNA molecules and as a means of computational simulation. This review surveys the rather limited literature that has explored these effects. Understanding the nature of CPDs is important in understanding traversal along fitness landscape valleys in evolution. It could also have applications in treating diseases that result from such mutations.
Pretreatment, Intratreatment, and Posttreatment EEG Imaging of EMDR: Methodology and Preliminary Results From a Single Case
Authors: Pagani Marco , Di Lorenzo Giorgio , Monaco Leonardo , Niolu Cinzia , Siracusano Alberto , Verardo Anna Rita , Lauretti Giada , Fernandez Isabel , Nicolais Giampaolo , Cogolo Patrizia , Ammaniti Massimo
Published: July 2011

Electroencephalography (EEG), due to its peculiar time and spatial resolution, was used for the first time to fully monitor neuronal activation during the whole eye movement desensitization and reprocessing (EMDR) session, including the autobiographical script. The present case report describes the dominant cortical activations (Z-score >1.5) during the first EMDR session and in the last session after the client processed the index trauma. During the first EMDR session, prefrontal limbic cortex was essentially activated during script listening and during lateral eye movements in the desensitization phase of EMDR. In the last EMDR session, the prevalent electrical activity was recorded in temporal, parietal, and occipital cortical regions, with a clear leftward lateralization. These findings suggest a cognitive processing of the traumatic event following successful EMDR therapy and support evidence of distinct neurobiological patterns of brain activations during lateral eye movements in the desensitization phase of EMDR.