bluuebunny/crossref_metadata_2025 huggingface dataset:
Employing volcanic tuff minerals in interior architecture design to reduce microbial contaminants and airborne fungal carcinogens of indoor environments
Authors: Gedikoglu Yaman , Gedikoglu Gunduz , Berkin Genco , Ceyhan Taskin , Altinoz Meric A
Published: November 2011

Indoor volatile organic compounds (VOCs) have posed significant risks to human health since people have both shifted to a life spent, for the most part, indoors. Further, changes in materials used in the construction of buildings, furnishings, and tools either leak or encourage the production of VOCs. Whether these enclosed areas are residences, hospitals or workplaces (specifically composting facilities or closed farm buildings for raising livestock), VOCs can rise to levels that threaten people’s health. VOCs can either originate from phenolic and benzene-like compounds in building materials and office furniture or from molds (fungi) growing inside improperly ventilated or sealed buildings. Regardless of the source, exposure to VOCs could lead to significant health concerns from sick-building syndrome, ‘leukemia houses,’ in-hospital fungemia cases or occupation-associated cancer epidemics due to aflatoxicosis. Innovative 21st-century building materials could offer solutions to these challenges. We propose that volcanic materials, clays and minerals (volcanic tuff, modified clay montmorillonite and mineral clinoptilolite), in their original or chemically modified form, could act like synthetic lungs in building walls, breathing and filtering VOCs, and thus limiting human exposure to disease.
Occupational genotoxicity among copper smelters
Authors: De Olivera Juliana Viégas Duarte , Boufleur Liana Appel , Santos Carla Eliete Iochims Dos , Dias Johnny Ferraz , Squeff Cíntia Haag , Silva Guilherme Ruivo Gonçalves , Ianistcki Martus , Benvegnú Vinícius Cosmos , Silva Juliana Da
Published: November 2011

Occupational exposure in a copper smelting industry may produce various adverse health effects including cancer. Despite a number of well-documented studies reporting an increased risk of cancer among copper smelter workers, the data on genotoxic effects in this industry are scarce. In view of the above, an assessment of DNA damage in peripheral blood leukocytes by Comet assay from copper smelter workers was undertaken. Additionally, the proton-induced X-ray emission (PIXE) analysis was assessed to determine the metal content of samples. The study was conducted with all workers from a copper smelter (males; n = 11), and a control group ( n = 11) was recruited. The results of our study showed a significant increase ( p < 0.001; Mann-Whitney test) in DNA damage in peripheral blood lymphocytes of smelter workers, compared to the controls ( p < 0.001; Mann-Whitney test). No correlation between DNA damage or metal concentration and age mean or time of exposure was found under study. Our findings indicate that copper smelter workers have increased levels of DNA damage in somatic cells, suggesting a potential health risk for the workers. PIXE results show the presence of copper, iron, and other metals.
Topology optimization of aeronautical structures with stress constraints: general methodology and applications
Authors: París J , Martínez S , Navarrina F , Colominas I , Casteleiro M
Published: November 2011

Structural optimization is a well known and frequently used discipline in aerospace applications since most of the optimization problems were stated in order to solve aeronautic structures. Since first works about structural topology optimization were published, different formulations have been proposed to obtain the most adequate design. Topology optimization of structures is the most recent branch of structural optimization. The first works about this topic were proposed by Bendsoe and Kikuchi in 1988 (Bendsoe, M. P. and Kikuchi, N. Generating optimal topologies in structural design using a homogenization method. Comput. Methods Appl. Mech. Engng., 1988, 71, 197–224). In this field of structural optimum design, the aim is to obtain the optimal material distribution of a given amount of material in a predefined domain. The most usual formulation tries to maximize the stiffness of the structure by using a given amount of material. In this paper, we present a minimum weight formulation with stress constraints that allows to avoid most of the drawbacks associated to maximum stiffness approaches. The proposed formulation is applied to the optimization of aeronautical structures. Some examples have been studied in order to validate the formulation proposed.
Mind Your Errors
Authors: Moser Jason S. , Schroder Hans S. , Heeter Carrie , Moran Tim P. , Lee Yu-Hao
Published: November 2011

How well people bounce back from mistakes depends on their beliefs about learning and intelligence. For individuals with a growth mind-set, who believe intelligence develops through effort, mistakes are seen as opportunities to learn and improve. For individuals with a fixed mind-set, who believe intelligence is a stable characteristic, mistakes indicate lack of ability. We examined performance-monitoring event-related potentials (ERPs) to probe the neural mechanisms underlying these different reactions to mistakes. Findings revealed that a growth mind-set was associated with enhancement of the error positivity component (Pe), which reflects awareness of and allocation of attention to mistakes. More growth-minded individuals also showed superior accuracy after mistakes compared with individuals endorsing a more fixed mind-set. It is critical to note that Pe amplitude mediated the relationship between mind-set and posterror accuracy. These results suggest that neural mechanisms indexing on-line awareness of and attention to mistakes are intimately involved in growth-minded individuals’ ability to rebound from mistakes.
Comparative risk analysis of electricity generating systems using the J-value framework
Authors: Kearns J O , Thomas P J , Taylor R H , Boyle W J O
Published: November 2011

Decisions regarding the implementation of different forms of electricity generating systems necessarily require consideration of a large number of social, economic, environmental, and technical indicators. One such important indicator is the effect on health. This article presents a comparative risk analysis of mortality impacts arising from the generation of electricity by nuclear, coal, gas, onshore wind, and offshore wind UK power plants. The risk analysis was carried out using the J-value method, which provides a common, objective scale by which human harm can be valued. The analysis assessed human mortality impacts arising from the construction of future plants over the 60-year period from 2010 to 2070 for the entire fuel chain. Despite the considerable uncertainties in current estimates, the analysis provides evidence of the worth of the J-value methodology, particularly in relation to its ability to take explicit account of loss of life expectancy in evaluating delayed health effects. Risks are delineated according to two dimensions: whether the risk is occupational or public, and whether the risk is immediate or delayed. Impacts are also assessed for major accidents. The results indicate that nuclear generally has the lowest impacts, while gas, onshore wind and offshore wind have indicative impacts that are about an order of magnitude greater, although the estimates for both wind technologies carry considerable uncertainty. Coal power was found to present high impacts compared with the other technologies, mainly as a result of pollution emissions, even though the potential harm from some emissions has not been included because the effects are not fully understood. Total nuclear impacts were found to be sensitive to assumptions regarding the use of collective dose and the assumptions which are then used to calculate impacts. For the most pessimistic case, when world exposures are taken, total nuclear impacts increase by about an order of magnitude, which would render the risks from nuclear generation comparable with those from gas and wind generation.
The mythologization of regression towards the mean
Authors: Maraun Michael D. , Gabriel Stephanie , Martin Jack
Published: November 2011

In the quantitative methodology literature, there now exists what can be considered a received account of the enigmatic phenomenon known as regression towards the mean (RTM), the origins of which can be traced to the work of Sir Francis Galton circa 1885. On the received account, RTM is, variably, portrayed as a ubiquitous, unobservable property of individual-level difference and change phenomena, a force that impacts upon the characteristics of individual entities, an explanation for difference and change phenomena, and a profound threat to the drawing of correct conclusions in experiments. In the current paper, we describe the most essential components of the received account, and offer arguments to the effect that the received account is a mythologization of RTM. In particular, we: (a) describe the scientific and statistical setting in which a consideration of RTM is embedded; (b) translate Galton’s discussion of RTM into modern statistical terms; (c) excavate a definition of the concept regression towards the mean from Galton’s discussion of RTM; and (d) employ the excavated definition to dismantle certain of the most essential components of the received account.
Cutaneous lupus erythematosus on the elbows: a peculiar localization
Authors: Bielsa I , Guinovart RM , Fernández-Figueras MT , Rodríguez C , Ferrándiz C
Published: November 2011

Background: The presence of lesions limited to the elbows as expression of a cutaneous lupus erythematosus (CLE) is very unusual.

Objectives: To describe the clinical and microscopic characteristics of these lesions, as well as their relationship with the different cutaneous lupus erythematosus subsets.

Methods: Seven cases of CLE with lesions on the elbows, collected from 1998 to 2009, were retrospectively analysed. All patients had a previous or concomitant diagnosis of lupus erythematosus based on other typical skin lesions for each subtype of lupus erythematosus, and they all met clinical and microscopic criteria.

Results: Six patients were women with a mean age of 33.8 years. Five cases had been previously diagnosed with CLE (three lupus erythematosus [LE] tumidus, one subacute CLE and one acute CLE). In the other two cases, these lesions were the first manifestation of the disease. The lesions consisted of pruriginous, erythematous papules and plaques with a slightly scaly surface, located on both elbows. Microscopically, in addition to the typical features of CLE, other changes were observed, including alterations in the texture and the staining properties of collagen fibres (five cases), an interstitial histiocytic infiltrate (four cases), eosinophils (one case) and a Churg–Strauss granuloma (one case).

Conclusions: These peculiar lesions located on the elbows should be included in the spectrum of cutaneous manifestations of LE. Their histopathology combines changes of both LE and interstitial granulomatous dermatitis.
What Is the Middle Income Trap, Why do Countries Fall into It, and How Can It Be Avoided?
Authors: Kharas Homi , Kohli Harinder
Published: November 2011

The risks of falling into the Middle Income Trap have increasingly become a focus of discussions on the long-term economic and social development prospects of developing countries. These risks, and how to minimize them, are being debated at the highest levels of policy making in some of the fastest growing emerging economies, even while these countries remain a source of envy to the rest of the world. The term Middle Income Trap is by now also being widely used in economic literature as well as business-oriented media. We draw satisfaction from the fact that some of our previous writings (Gill and Kharas, 2008; Kohli et al. 2009) (co-authored with other colleagues) seem to have helped popularize this term. At the same time, we realize that some have interpreted and used the term quite differently from what we had in mind when we first introduced the term Middle Income Trap in our writings and presentations. This article offers our perspective as to what the Middle Income Trap is, why so many countries fall into it, and the key challenges involved in avoiding the trap. With policy makers as its primary audience, the article is deliberately short in length and straightforward in language.
Productivity and Technology for Asia’s Growth
Authors: Sood Anil , Szyf Y. Aaron
Published: November 2011

For Asia to realize the Asian Century in 2050 and reach per capita income levels similar to Europe today, its fast-growing converging economies must sustain their growth momentum. The slower growing countries must accelerate their growth to achieve convergence status during this period. The underlying requirement for both groups is continued rapid improvement in total factor productivity (TFP). Although it may sound ambitious and though it is definitely not preordained, Asia can reach this dream if its economies strive for excellence in the areas of productivity and innovation, while learning from the best practice in the region and beyond. This article addresses the TFP level and performance of Asian economies, the salient underlying factors, and the strategies that Asian economies must pursue to make further improvement.
The Challenge of Governance and Institutions for Asia
Authors: Katsu Shigeo
Published: November 2011

It is essential for all Asian countries to focus on improving governance and transforming institutions in order to meet the challenges of the coming decades. The recent deterioration in the quality and credibility of national political and economic institutions in a large number of Asian countries is a key concern and a reason why Asia’s rise should not be seen as preordained. Transparency, predictability and accountability are key elements to establishing long-term domestic legitimacy of authorities. These make governance and institutional dimensions, even over a 40 year time horizon, a good basis for discussing the broad direction of Asia, and stakeholders should not wait for too long to start preparing for 2050. This article discusses the drivers for change, and the demand side for changes or reforms in governance, and institutions, and it subsequently addresses possible ways forward.
Regional Integration and Cooperation in Asia—An Indian Perspective
Authors: Das Ram Upendra , Vasudev C.M. , Gupta Madhukar
Published: November 2011

Regional cooperation and regional integration are terms that are often used synonymously, although they differ in important respects. Regional cooperation most often encompasses policies and agreements relating to matters such as preferential or free trade agreements entailing the removal of trade barriers for trade in goods; Economic Partnership Agreements (EPAs)/Comprehensive Economic Cooperation Agreements (CECAs) covering market access in trade and services besides trade in goods, as also cooperation for investment promotion and protection; among others. Regional integration on the other hand may mean deeper forms of cooperation that could include an alignment of customs regimes; the coordination in macroeconomic policies; a freer movement of factors of production like labor and capital; cross border connectivity, communications and energy related linkages; a common central bank. This article presents an overview of the Asian region and how some of the key features of Asia have influenced the Indian perspective on regional integration and cooperation. It elaborates upon some of the major drivers of current and future integration processes in Asia, as well as the dynamics and interplay of various factors and forces that may point towards the potential for Asian integration.
Physical Activity and Body Mass Perception
Authors: Anderson Darrin W. , Libonati Joseph R.
Published: November 2011

Purpose:

To evaluate ethnic perceptual variations in body mass index (BMI) and accrued physical activity. Women ( n = 204) from the eastern United States were stratified into the following ethnic groups: White women (WW; n = 97), Black women (BW n = 62) and Others (Hispanic and Asian women, n = 45). Participants completed questionnaires and physiologic variables were determined. BW had increased weight, BMI, waist circumference, and body fat percentage vs. WW ( p < .05). Body mass was higher in BW vs. Others (p < .05). There were no differences for perception of BMI or body dissatisfaction. BW were the only group in which perception of BMI was lower than measured BMI. BW engaged in 50% less domestic and total physical activity than WW and Others. Physical activity was not correlated to perception of BMI.

Conclusion:

Perception of BMI was similar across ethnic groups and not correlated to physical activity levels in young women.
Debt Policy and Corporate Choice of Organizational Form
Authors: Joulfaian David
Published: November 2011

Corporate income is taxed twice, once at the entity level and then taxed once again at the shareholder level. In addition, the corporate tax system favors debt over equity financing of capital expenditures; corporations are able to deduct interest on borrowed funds, unlike the return to equity. By excessive borrowing, corporations are able to reduce the burden of double taxation. In contrast, noncorporate entities such as S corporations and partnerships are only taxed once at the shareholder level. Switching their organizational form, say from C to S corporate status, allows firms to engage in a form of self-help integration and avoid double taxation. But do C corporations that switch their organizational form to the S status less leveraged? The evidence suggests that they do, albeit modestly, and may provide further support to the incentive effects of taxes on debt policy.
Screening for the risk of job loss in multiple sclerosis (MS): development of an MS-specific Work Instability Scale (MS-WIS)
Authors: McFadden Estelle , Horton Mike C , Ford Helen L , Gilworth Gill , McFadden Majella , Tennant Alan
Published: November 2011

Background: Multiple Sclerosis (MS) mainly presents amongst those of working age. Depending upon the type of MS, many people embark upon a long period of managing their day-to-day work-related needs in the face of intermittent and sometimes persistent disabling symptoms. The objective of this study was to explore the concept of work instability (WI) following the onset of MS and develop a Work Instability Scale (WIS) specific to this population.

Method: WI amongst those with MS in work was explored through qualitative interviews which were then used to generate items for a WIS. Rasch analysis was used to refine the scaling properties of the MS-WIS, which was then validated against expert vocational assessment by occupational health physiotherapists and ergonomists.

Results: The resulting measure is a 22-item, self-administered scale which can be scored in three bands indicating low, medium and high risk of WI (job retention) problems. The scale meets modern psychometric requirements for measurement, indicated by adequate fit to the Rasch model with absence of local dependency and differential item functioning (DIF) by age, gender and hours worked.

Conclusions: The scale presents an opportunity in routine clinical practice to take positive action to reduce sickness absence and prevent job loss.
Disappearance of cerebrospinal fluid oligoclonal bands after natalizumab treatment of multiple sclerosis patients
Authors: von Glehn Felipe , Farias Alessandro S , de Oliveira Augusto C Penalva , Damasceno Alfredo , Longhini Ana Leda F , Oliveira Elaine C , Damasceno Benito P , Santos Leonilda MB , Brandão Carlos Otávio
Published: November 2011

Intrathecal immunoglobulin synthesis in an oligoclonal pattern is the most common immunologic abnormality detected in MS patients. Various treatments, such as immunomodulators and immunosuppressors, have not been found to modify it. Natalizumab hinders migration of encephalitogenic T-cells into the central nervous system (CNS), reducing inflammatory response. Its impact on CSF oligoclonal bands (OCBs) has not been demonstrated. This report describes its effect in four out of six patients with multiple sclerosis after a mean of 10 infusions: the CSF was negative for OCBs at the second lumbar puncture. In conclusion, natalizumab treatment can reduce CSF OCBs to undetectable levels, although the clinical significance of this observation is not yet known.
Spatialities of Skin: The Chafing of Skin, Ego and Second Skins in T.E. Lawrence’s Seven Pillars of Wisdom
Authors: Pile Steve
Published: November 2011

This article explores the relationship between skin, ego and second skins. It does so conceptually by re-examining Freud’s suggestion, in The Ego and the Id, that the ego is first and foremost a bodily entity, while also being a projection of a surface (i.e. skin). Drawing upon Anzieu, a dynamic model of inter-weaving surfaces can be seen to underpin an understanding of the ego — and skin ego. This model is fundamentally spatialized. Even so, an appreciation of the spatialities of skin and ego can be developed further. To illuminate these spatialities, this article examines two key experiences of T.E. Lawrence during his military service in Arabia (c. 1917), as he describes them in his autobiographical account Seven Pillars of Wisdom. In a meeting with British military police, and in the notorious Deraa rape incident, what is at stake is Lawrence of Arabia’s skins. Reading these experiences using Freud and Anzieu, the article argues that these events re-present an ongoing chafing of Lawrence’s skin, ego and second skins, which can be called his ‘skin of suffering’.
The surgical management of painful nerves of the upper limb: a unit perspective
Authors: Elliot D. , Sierakowski A.
Published: November 2011

Some patients develop excessive peripheral nerve pain beyond that normally experienced after injury or surgery. Managing this pain can be a difficult and frustrating experience for both the surgeon and patient concerned. We present a system for the classification, assessment and treatment of painful neuromas of the upper limb.
In the clinic: ongoing clinical trials evaluating c-MET-inhibiting drugs
Authors: Sharma Neelesh , Adjei Alex A.
Published: November 2011

The c-MET (mesenchymal–epithelial transition factor) pathway is dysregulated in many human cancers and promotes tumor growth, invasion and dissemination. The c-MET receptor tyrosine kinase can be activated via gene mutation, gene amplification, protein overexpression and/or a ligand-dependent autocrine/paracrine loop. Abnormalities in c-MET signaling have been reported to correlate with poor clinical outcomes and drug resistance in patients with cancer. Significant progress has been made in advancement of c-MET pathway inhibitors through to clinical trials. A robust pipeline of high-quality inhibitors targeting different aspects of c-MET activation is currently being explored in phase I, II and III clinical trials across multiple tumor types. Preliminary data demonstrate promising clinical activity with these agents, along with an acceptable toxicity profile. In this manuscript, the pharmacological profile of drugs targeting the c-MET pathway and available data from ongoing clinical trials of these drugs are discussed.
Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease
Authors: D'Souza Sonia , del Prete Davide , Jin Shunqian , Sun Quanhong , Huston Alissa J. , Kostov Flavia Esteve , Sammut Benedicte , Hong Chang-Sook , Anderson Judith L. , Patrene Kenneth D. , Yu Shibing , Velu Chinavenmeni S. , Xiao Guozhi , Grimes H. Leighton , Roodman G. David , Galson Deborah L.
Published: November 2011

Protracted inhibition of osteoblast (OB) differentiation characterizes multiple myeloma (MM) bone disease and persists even when patients are in long-term remission. However, the underlying pathophysiology for this prolonged OB suppression is unknown. Therefore, we developed a mouse MM model in which the bone marrow stromal cells (BMSCs) remained unresponsive to OB differentiation signals after removal of MM cells. We found that BMSCs from both MM-bearing mice and MM patients had increased levels of the transcriptional repressor Gfi1 compared with controls and that Gfi1 was a novel transcriptional repressor of the critical OB transcription factor Runx2. Trichostatin-A blocked the effects of Gfi1, suggesting that it induces epigenetic changes in the Runx2 promoter. MM-BMSC cell-cell contact was not required for MM cells to increase Gfi1 and repress Runx2 levels in MC-4 before OBs or naive primary BMSCs, and Gfi1 induction was blocked by anti–TNF-α and anti–IL-7 antibodies. Importantly, BMSCs isolated from Gfi1−/− mice were significantly resistant to MM-induced OB suppression. Strikingly, siRNA knockdown of Gfi1 in BMSCs from MM patients significantly restored expression of Runx2 and OB differentiation markers. Thus, Gfi1 may have an important role in prolonged MM-induced OB suppression and provide a new therapeutic target for MM bone disease.
Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1α levels in patients with MGUS
Authors: Ng Alvin C. , Khosla Sundeep , Charatcharoenwitthaya Natthinee , Kumar Shaji K. , Achenbach Sara J. , Holets Margaret F. , McCready Louise K. , Melton L. Joseph , Kyle Robert A. , Rajkumar S. Vincent , Drake Matthew T.
Published: November 2011

Recent population-based studies demonstrate an increased fracture risk with monoclonal gammopathy of undetermined significance (MGUS). The etiology of this increased risk remains unclear, however, because areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry cannot assess bone microstructural properties critical to determining bone quality and strength. To better define the skeletal effects of MGUS, we performed aBMD and high-resolution peripheral quantitative computed tomography volumetric bone mineral density (vBMD) measurements in 50 MGUS patients (20 females, 30 males; mean ± SEM age, 70.5 ± 1.4 years) and 100 matched control subjects. Relative to controls, MGUS patients had decreased aBMD at the femoral neck (P = .05) and total femur (P < .05) but no differences at other sites. In contrast, high-resolution peripheral quantitative computed tomography showed markedly diminished cortical thickness (P < .05) and increased endocortical area (P < .01). Average vBMD (P < .01), cortical vBMD (P < .001), and trabecular thickness (P < .01) were all significantly decreased in MGUS patients, suggestive of impaired bone formation. Serum levels of the Wnt pathway inhibitor Dickkopf-related protein 1 (P < .001) and osteoclast-activating factor MIP-1α (P < .05) also were significantly elevated in MGUS patients. Our data provide the first evidence of altered bone microstructure in MGUS and suggest that cytokines elevated in osteolytic myeloma also may be associated with bone loss in MGUS.
B-cell replication history and somatic hypermutation status identify distinct pathophysiologic backgrounds in common variable immunodeficiency
Authors: Driessen Gertjan J. , van Zelm Menno C. , van Hagen P. Martin , Hartwig Nico G. , Trip Margreet , Warris Adilia , de Vries Esther , Barendregt Barbara H. , Pico Ingrid , Hop Wim , van Dongen Jacques J. M. , van der Burg Mirjam
Published: November 2011

Common variable immunodeficiency disorder (CVID) is the most prevalent form of primary idiopathic hypogammaglobulinemia. Identification of genetic defects in CVID is hampered by clinical and immunologic heterogeneity. By flow cytometric immunophenotyping and cell sorting of peripheral B-cell subsets of 37 CVID patients, we studied the B-cell compartment at the B-cell subset level using the κ-deleting recombination excision circle assay to determine the replication history and the Igκ-restriction enzyme hot-spot mutation assay to assess the somatic hypermutation status. Using this approach, 5 B-cell patterns were identified, which delineated groups with unique replication and somatic hypermutation characteristics. Each B-cell pattern reflected an immunologically homogenous patient group for which we proposed a different pathophysiology: (1) a B-cell production defect (n = 8, 18%), (2) an early peripheral B-cell maturation or survival defect (n = 4, 11%), (3) a B-cell activation and proliferation defect (n = 12, 32%), (4) a germinal center defect (n = 7, 19%), and (5) a postgerminal center defect (n = 6, 16%). The results of the present study provide for the first time insight into the underlying pathophysiologic background in 5 immunologically homogenous groups of CVID patients. Moreover, this study forms the basis for larger cohort studies with the defined homogenous patient groups and will facilitate the identification of underlying genetic defects in CVID.
Critical role for perforin and Fas-dependent killing of dendritic cells in the control of inflammation
Authors: Chen Min , Felix Kumar , Wang Jin
Published: November 2011

After stimulation of antigen-specific T cells, dendritic cell (DCs) are susceptible to killing by these activated T cells that involve perforin and Fas-dependent mechanisms. Fas-dependent DC apoptosis has been shown to limit DC accumulation and prevent the development of autoimmunity. However, a role for perforin in the maintenance of DC homeostasis for immune regulation remains to be determined. Here we show that perforin deficiency in mice, together with the deletion of Fas in DCs (perforin−/−DC-Fas−/−), led to DC accumulation, uncontrolled T-cell activation, and IFN-γ production by CD8+ T cells, resulting in the development of lethal hemophagocytic lymphohistiocytosis. Consistently, adoptive transfer of Fas−/− DCs induced over-activation and IFN-γ production in perforin−/− CD8+ T cells. Neutralization of IFN-γ prevented the spreading of inflammatory responses to different cell types and protected the survival of perforin−/−DC-Fas−/− mice. Our data suggest that perforin and Fas synergize in the maintenance of DC homeostasis to limit T cell activation, and prevent the initiation of an inflammatory cascade.
Purinergic signaling inhibits human acute myeloblastic leukemia cell proliferation, migration, and engraftment in immunodeficient mice
Authors: Salvestrini Valentina , Zini Roberta , Rossi Lara , Gulinelli Sara , Manfredini Rossella , Bianchi Elisa , Piacibello Wanda , Caione Luisa , Migliardi Giorgia , Ricciardi Maria Rosaria , Tafuri Agostino , Romano Marco , Salati Simona , Di Virgilio Francesco , Ferrari Sergio , Baccarani Michele , Ferrari Davide , Lemoli Roberto M.
Published: November 2011

Extracellular ATP and UTP nucleotides increase the proliferation and engraftment potential of normal human hematopoietic stem cells via the engagement of purinergic receptors (P2Rs). In the present study, we show that ATP and UTP have strikingly opposite effects on human acute myeloblastic leukemia (AML) cells. Leukemic cells express P2Rs. ATP-stimulated leukemic cells, but not normal CD34+ cells, undergo down-regulation of genes involved in cell proliferation and migration, whereas cell-cycle inhibitors are up-regulated. Functionally, ATP induced the inhibition of proliferation and accumulation of AML cells, but not of normal cells, in the G0 phase of the cell cycle. Exposure to ATP or UTP inhibited AML-cell migration in vitro. In vivo, xenotransplantation experiments demonstrated that the homing and engraftment capacity of AML blasts and CD34+CD38− cells to immunodeficient mice BM was significantly inhibited by pretreatment with nucleotides. P2R-expression analysis and pharmacologic profiling suggested that the inhibition of proliferation by ATP was mediated by the down-regulation of the P2X7R, which is up-regulated on untreated blasts, whereas the inhibition of chemotaxis was mainly mediated via P2Y2R and P2Y4R subtypes. We conclude that, unlike normal cells, P2R signaling inhibits leukemic cells and therefore its pharmacologic modulation may represent a novel therapeutic strategy.
Comparative analysis of neural transcriptomes and functional implication of unannotated intronic expression
Authors: Sun Yazhou , Wang Yaqiong , Hu Yi , Chen Gong , Ma Hong
Published: November 2011

Background

The transcriptome and its regulation bridge the genome and the phenome. Recent RNA-seq studies unveiled complex transcriptomes with previously unknown transcripts and functions. To investigate the characteristics of neural transcriptomes and possible functions of previously unknown transcripts, we analyzed and compared nine recent RNA-seq datasets corresponding to tissues/organs ranging from stem cell, embryonic brain cortex to adult whole brain.

Results

We found that the neural and stem cell transcriptomes share global similarity in both gene and chromosomal expression, but are quite different from those of liver or muscle. We also found an unusually high level of unannotated expression in mouse embryonic brains. The intronic unannotated expression was found to be strongly associated with genes annotated for neurogenesis, axon guidance, negative regulation of transcription, and neural transmission. These functions are the hallmarks of the late embryonic stage cortex, and crucial for synaptogenesis and neural circuit formation.

Conclusions

Our results revealed unique global and local landscapes of neural transcriptomes. It also suggested potential functional roles for previously unknown transcripts actively expressed in the developing brain cortex. Our findings provide new insights into potentially novel genes, gene functions and regulatory mechanisms in early brain development.
De novo sequence assembly of Albugo candida reveals a small genome relative to other biotrophic oomycetes
Authors: Links Matthew G , Holub Eric , Jiang Rays HY , Sharpe Andrew G , Hegedus Dwayne , Beynon Elena , Sillito Dean , Clarke Wayne E , Uzuhashi Shihomi , Borhan Mohammad H
Published: November 2011

Background

Albugo candida is a biotrophic oomycete that parasitizes various species of Brassicaceae, causing a disease (white blister rust) with remarkable convergence in behaviour to unrelated rusts of basidiomycete fungi.

Results

A recent genome analysis of the oomycete Hyaloperonospora arabidopsidis suggests that a reduction in the number of genes encoding secreted pathogenicity proteins, enzymes for assimilation of inorganic nitrogen and sulphur represent a genomic signature for the evolution of obligate biotrophy. Here, we report a draft reference genome of a major crop pathogen Albugo candida (another obligate biotrophic oomycete) with an estimated genome of 45.3 Mb. This is very similar to the genome size of a necrotrophic oomycete Pythium ultimum (43 Mb) but less than half that of H. arabidopsidis (99 Mb). Sequencing of A. candida transcripts from infected host tissue and zoosporangia combined with genome-wide annotation revealed 15,824 predicted genes. Most of the predicted genes lack significant similarity with sequences from other oomycetes. Most intriguingly, A. candida appears to have a much smaller repertoire of pathogenicity-related proteins than H. arabidopsidis including genes that encode RXLR effector proteins, CRINKLER-like genes, and elicitins. Necrosis and Ethylene inducing Peptides were not detected in the genome of A. candida. Putative orthologs of tat-C, a component of the twin arginine translocase system, were identified from multiple oomycete genera along with proteins containing putative tat-secretion signal peptides.

Conclusion

Albugo candida has a comparatively small genome amongst oomycetes, retains motility of sporangial inoculum, and harbours a much smaller repertoire of candidate effectors than was recently reported for H. arabidopsidis. This minimal gene repertoire could indicate a lack of expansion, rather than a reduction, in the number of genes that signify the evolution of biotrophy in oomycetes.
Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels?
Authors: Pepper Ruth , Campbell Neil , Yaqoob Magdi M , Roberts Norman B , Fan Stanley L-S
Published: November 2011

Background

Aluminium (Al) toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps) whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water.

Methods

HD patients only treated with Reverse Osmosis(RO) treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies.

Results

39 patients (34 anuric) were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration) and the total amount of Al ingested.

No patients had unexplained EPO resistance or biochemical evidence of adynamic bone.

Conclusions

Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R2 = 0.07) and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric.
An integrated systems biology approach to the study of preterm birth using "-omic" technology - a guideline for research
Authors: Gracie Sara , Pennell Craig , Ekman-Ordeberg Gunvor , Lye Stephen , McManaman James , Williams Scott , Palmer Lyle , Kelley Maureen , Menon Ram , Gravett Michael ,   the PREBIC "-Omics" Research Group
Published: November 2011

Preterm birth is the leading cause of neonatal mortality and perinatal morbidity. The etiology of preterm is multi-factorial and still unclear. As evidence increases for a genetic contribution to PTB, so does the need to explore genomics, transcriptomics, proteomics and metabolomics in its study. This review suggests research guidelines for the conduct of high throughput systems biology investigations into preterm birth with the expectation that this will facilitate the sharing of samples and data internationally through consortia, generating the power needed to study preterm birth using integrated "-omics" technologies. The issues to be addressed include: (1) integrated "-omics" approaches, (2) phenotyping, (3) sample collection, (4) data management-integrative databases, (5) international consortia and (6) translational feasibility. This manuscript is the product of discussions initiated by the "-Omics" Working Group at the Preterm Birth International Collaborative Meeting held at the World Health Organization, Geneva, Switzerland in April 2009.
An integrated structural intervention to reduce vulnerability to HIV and sexually transmitted infections among female sex workers in Karnataka state, south India
Authors: Gurnani Vandana , Beattie Tara S , Bhattacharjee Parinita ,   CFAR Team, Mohan HL , Maddur Srinath , Washington Reynold , Isac Shajy , Ramesh BM , Moses Stephen , Blanchard James F
Published: November 2011

Background

Structural factors are known to affect individual risk and vulnerability to HIV. In the context of an HIV prevention programme for over 60,000 female sex workers (FSWs) in south India, we developed structural interventions involving policy makers, secondary stakeholders (police, government officials, lawyers, media) and primary stakeholders (FSWs themselves). The purpose of the interventions was to address context-specific factors (social inequity, violence and harassment, and stigma and discrimination) contributing to HIV vulnerability. We advocated with government authorities for HIV/AIDS as an economic, social and developmental issue, and solicited political leadership to embed HIV/AIDS issues throughout governmental programmes. We mobilised FSWs and appraised them of their legal rights, and worked with FSWs and people with HIV/AIDS to implement sensitization and awareness training for more than 175 government officials, 13,500 police and 950 journalists.

Methods

Standardised, routine programme monitoring indicators on service provision, service uptake, and community activities were collected monthly from 18 districts in Karnataka between 2007 and 2009. Daily tracking of news articles concerning HIV/AIDS and FSWs was undertaken manually in selected districts between 2005 and 2008.

Results

The HIV prevention programme is now operating at scale, with over 60,000 FSWs regularly contacted by peer educators, and over 17,000 FSWs accessing project services for sexually transmitted infections monthly. FSW membership in community-based organisations has increased from 8,000 to 37,000, and over 46,000 FSWs have now been referred for government-sponsored social entitlements. FSWs were supported to redress > 90% of the 4,600 reported incidents of violence and harassment reported between 2007-2009, and monitoring of news stories has shown a 50% increase in the number of positive media reports on HIV/AIDS and FSWs.

Conclusions

Stigma, discrimination, violence, harassment and social equity issues are critical concerns of FSWs. This report demonstrates that it is possible to address these broader structural factors as part of large-scale HIV prevention programming. Although assessing the impact of the various components of a structural intervention on reducing HIV vulnerability is difficult, addressing the broader structural factors contributing to FSW vulnerability is critical to enable these vulnerable women to become sufficiently empowered to adopt the safer sexual behaviours which are required to respond effectively to the HIV epidemic.
Apoptosis, mastocytosis, and diminished adipocytokine gene expression accompany reduced epididymal fat mass in long-standing diet-induced obese mice
Authors: Altintas Mehmet M , Rossetti Maria A , Nayer Behzad , Puig Alvaro , Zagallo Patricia , Ortega Luis M , Johnson Kevin B , McNamara George , Reiser Jochen , Mendez Armando J , Nayer Ali
Published: November 2011

Background

Obesity is characterized by increased cell death and inflammatory reactions in the adipose tissue. Here, we explored pathophysiological alterations taking place in the adipose tissue in long-standing obesity. In the epididymal fat of C57BL/6 mice fed a high-fat diet for 20 weeks, the prevalence and distribution of dead adipocytes (crown-like structures), mast cells (toluidine blue, mMCP6), macrophages (F4/80), and apoptotic cells (cleaved caspase-3) were measured. Moreover, gene and/or protein expression of several adipocytokines (leptin, adiponectin, TNF-α, IL-10, IL-6, MCP-1), F4/80, mMCP6, cleaved caspase-3 were determined.

Results

We observed that the epididymal fat mass was lower in obese than in lean mice. In obese mice, the epididymal fat mass correlated inversely with body weight and liver mass. Dead adipocytes, mast cells, macrophages, and apoptotic cells were abundant in the epididymal fat of obese mice, especially in the rostral vs. caudal zone. Accordingly, mMCP6, F4/80, and cleaved caspase-3 gene and/or protein expression was increased. Conversely, adiponectin, leptin, IL-6, and MCP-1 gene expression levels were lower in the epididymal fat of obese than lean mice. Although TNF-α and IL-10 gene expression was higher in the epididymal fat of obese mice, their expression relative to F4/80 and mMCP6 expression were lower in the heavily infiltrated rostral than caudal zone.

Conclusions

This study demonstrates that in mice with long-standing obesity diminished gene expression of several adipocytokines accompany apoptosis and reduced mass of the epididymal fat. Our findings suggest that this is due to both increased prevalence of dead adipocytes and altered immune cell activity. Differential distribution of metabolically challenged adipocytes is indicative of the presence of biologically diverse zones within the epididymal fat.
Embryotoxicity assays for leached components from dental restorative materials
Authors: Libonati Antonio , Marzo Giuseppe , Klinger Francesca G , Farini Donatella , Gallusi Gianni , Tecco Simona , Mummolo Stefano , De Felici Massimo , Campanella Vincenzo
Published: November 2011

Background

Currently, there are no suitable assays available to evaluate the embryotoxicity of leached components from restorative dental materials.

Methods

The effect of the medium conditioned by composites and amalgam on mouse blastocysts in vitro was tested. The materials were also subcutaneously implanted, and the effect of the medium supplemented with serum from the host blood was evaluated in the embryotoxicity assay. The embryo implantation rate in the material-transplanted mothers was also evaluated.

Results

The results show that while the culture in media conditioned by amalgams did not affect blastocyst development, the medium conditioned by composites caused blastocyst degeneration and apoptosis. The development of blastocysts in a medium containing serum obtained from animals after transplantation was, however, without effect. Finally, inconsistent reduction in the implantation rate in transplanted mothers was observed.

Conclusions

In this study, we provide examples of in vitro and in vivo tests that may be used to evaluate embryotoxicity for dental materials. Our results show that leached components from our composite-material induced embryotoxicity in vitro, however, no toxicity was observed when subcutaneously implanted in vivo. This highlights the necessity of integrated in vitro and in vivo tests for valuable predictive estimation of embryotoxicity for complex materials.
Gold-silver alloy nanoshells: a new candidate for nanotherapeutics and diagnostics
Authors: Gheorghe Dana E , Cui Lili , Karmonik Christof , Brazdeikis Audrius , Penaloza Jose M , Young Joseph K , Drezek Rebekah A , Bikram Malavosklish
Published: November 2011

We have developed novel gold-silver alloy nanoshells as magnetic resonance imaging (MRI) dual T1 (positive) and T2 (negative) contrast agents as an alternative to typical gadolinium (Gd)-based contrast agents. Specifically, we have doped iron oxide nanoparticles with Gd ions and sequestered the ions within the core by coating the nanoparticles with an alloy of gold and silver. Thus, these nanoparticles are very innovative and have the potential to overcome toxicities related to renal clearance of contrast agents such as nephrogenic systemic fibrosis. The morphology of the attained nanoparticles was characterized by XRD which demonstrated the successful incorporation of Gd(III) ions into the structure of the magnetite, with no major alterations of the spinel structure, as well as the growth of the gold-silver alloy shells. This was supported by TEM, ICP-AES, and SEM/EDS data. The nanoshells showed a saturation magnetization of 38 emu/g because of the presence of Gd ions within the crystalline structure with r1 and r2 values of 0.0119 and 0.9229 mL mg-1 s-1, respectively (Au:Ag alloy = 1:1). T1- and T2-weighted images of the nanoshells showed that these agents can both increase the surrounding water proton signals in the T1-weighted image and reduce the signal in T2-weighted images. The as-synthesized nanoparticles exhibited strong absorption in the range of 600-800 nm, their optical properties being strongly dependent upon the thickness of the gold-silver alloy shell. Thus, these nanoshells have the potential to be utilized for tumor cell ablation because of their absorption as well as an imaging agent.