bluuebunny/crossref_metadata_2025 huggingface dataset:
The production of space in metropolitan regions: A Lefebvrian analysis of governance and spatial change
Authors: Buser Michael
Published: March 2012

The language of relational geography now permeates the field and literature of planning, with phrases such as ‘fuzzy boundaries’ and ‘flows and networks’ being commonly used to express the complexity of socio-economic and governance relations. However, recent research suggests the so-called ‘relational turn’ is not only far from complete, but is unable to account for the bounded reality of urban processes.

Following from these debates, this article seeks to redirect the study of urban change away from relational and absolute interpretations of space in favour of a more robust consideration and critical reflection on the social production of city-regions. Towards this objective, the author introduces an approach situated within Lefebvre’s The Production of Space to examine strategies of metropolitan regionalism in the Capital District, New York (United States). Interpreting the city-region as a social product reflecting the co-constitutive relationship of conceived, perceived and lived space spatial elements, the paper argues that the silences of lived space within metropolitan regionalism are indicative of a post-political condition where hegemonic vision, discourse and ideology deny a robust urban democracy. It is this ability to engage with the dynamism of social change and the relationships between spaces which makes Lefebvre’s spatial theory immensely valuable for the study of emerging and shifting structures of governance.
Autonomy-facilitation or autonomy-promotion? The case of sex education
Authors: Corngold Josh
Published: March 2012

This article offers a critique of Harry Brighouse’s ‘autonomy-facilitating education’, which aims to enable students to reflect critically on their lives and society without disposing them to do so. Because it is ‘character-neutral’, this kind of education purportedly avoids some of the controversy surrounding autonomy-promotion. At the same time, it allegedly equips students to withstand common pressures and influences which jeopardize their prospective autonomy. Yet, as I argue here, autonomy-facilitating education cannot live up to the promises Brighouse makes for it. As the case of sex education exemplifies, students need more than a toolbox of rational skills to overcome persistent threats to their autonomy. They need access to an autonomy- promoting education that attends to their cognitive and psychosocial development.
Comments on Big Ideas for Little Kids
Authors: Kelly James S.
Published: March 2012

Thomas Wartenberg offers his book as a guide that will provide elementary school teachers what they need to facilitate philosophical discussions with children. My concerns are centered on the nature and role of philosophical discussion, the level of philosophical acumen needed for facilitating such discussion, and the role of character development in this educational adventure.
Addressing Disparities in Access to Care
Authors: DeGuzman Pamela B. , Keeling Arlene W.
Published: March 2012

Health disparities for racial and ethnic minorities have been present in the United States and persist today. NMHCs (Nurse-Managed Health Center), which can serve as “Medical Homes,” are one mechanism by which nurses can attempt to overcome these disparities within communities. In the mid-1960s, Nancy Milio developed and found funding for a NMHC to address disparities in Detroit, Michigan. History shows that the center was so valued by community members that it remained untouched during the Detroit riot of 1967, despite all buildings surrounding it having been burned down or destroyed. This article uses traditional historic methods to describe the establishment of the center in inner-city Detroit in the 1960s in historical context and analyze factors that led to Milio’s success. To address disparities via NMHCs, nurses must be persistent in acquiring funding and should involve a racially and culturally diverse group representative of community members in the development, planning, and ongoing operation of the enterprise.
Simulation modeling for maritime port security
Authors: Harris Stephen P , Dixon David S , Dunn David L , Romich Andrew N
Published: March 2012

United States ports must be prepared for the threat of a small-vessel attack using weapons of mass destruction (WMD). To reduce the risk of such an attack, modeling was conducted at the Savannah River National Laboratory (SRNL) in Aiken, South Carolina, to develop options for redeployment of existing maritime law enforcement resources, deployment of new resources, and optimal use of geographic terrain. Agent-based modeling (ABM) implemented by the Automated Vulnerability Evaluation for Risks of Terrorism (AVERT®) software was used to conduct computer-based simulation modeling. The port-specific models provided estimates for the probability of encountering an adversary based on allocated resources under varying environmental conditions and traffic flow rates. Defensive resources include patrol and response platforms, some of which may be more appropriate in particular environmental conditions. A diverse range of potential adversary and attack scenarios was assessed for a large area port and also for a port with a narrow inlet, thereby identifying vulnerable pathways. For chokepoint operations, the probability of encountering an adversary was estimated for various configurations and operational tempos. As traffic flow increased, the probability of encountering an adversary decreased because the adversary could assimilate into traffic, while security forces were preoccupied inspecting pleasure craft. However, there was a significant increase in the probability of encountering an adversary ( P(Encounter)) when additional patrols were added. Noted was a decreasing marginal benefit of additional patrols at low traffic levels. In open water, use of helicopters on patrol substantially increased the P(Encounter) by directing on-water security to target vessels. This capability was due to the far-reaching vision and speed capabilities of helicopters. As a result of ABM, more effective countermeasures can be deployed with available resources to reduce the risk of a small-vessel attack using WMD. The models can be expanded to all ports in the United States using generic models similar to those presented herein that can be matched to any port based on its size and shape.
Teachers’ Perceptions of Individual Performance-related Pay in Practice: A Picture of a Counterproductive Pay System
Authors: Lundström Ulf
Published: March 2012

This article describes and discusses Swedish upper-secondary teachers’ perceptions of the effects of individual performance-related pay (PRP) in the context of educational restructuring and governance. The empirical data were generated through semi-structured interviews of 23 teachers. Power’s distinction between programmatic and technological elements of audit is used as a frame of reference for the problematization of the pay system. The findings demonstrate a wide gap between the programmatic goals and their fulfilment in practice. The ability of the pay system to deliver its main objective, to enhance motivation by rewarding good performance, is questioned. The performance assessment criteria are neither well known nor motivate the teachers, and they perceive the appraisal as arbitrary and unfair, with a tendency to reward work of peripheral significance. Employers and teachers are supposed to engage in salary-setting dialogues, but in some cases these dialogues are neglected, and when they do occur the employers frequently do not explain how the quality of their performance is appraised. Implications for the teaching profession are discussed. The study indicates that the PRP system contributes to a shift from occupational to organizational professionalism and challenges a common work culture.
Leading and Managing in the Early Years: A Study of the Impact of a NCSL Programme on Children’s Centre Leaders’ Perceptions of Leadership and Practice
Authors: Ang Lynn
Published: March 2012

Research has shown that the quality of early years provisions is directly linked to the quality of leadership and management of early years settings. The extant research also shows that the quality of preschool settings are almost always characterised by strong leadership, where leaders and practitioners share a clear vision of the setting's practices. This paper presents the key findings of a national evaluation of early years leadership across a range of children centres in England. The focus of the study is to explore children's centre leaders' perceptions of leadership, and the impact of their professional qualification -°©- the National Professional Qualification in Integrated Centre Leadership (NPQICL) -°©- on their professional practice. Introduced by the National College for Leadership of Schools and Children's Services in 2005, the NPQICL was developed to support the professional needs of children's centre leaders, especially in the role they play in meeting the Every Child Matters (2003) outcomes for all young children. The findings reveal that integrated and multi-agency working, reflective learning and practice, as well as professional status and pay, are key factors that can significantly influence the role of children's centre leaders and which in turn has a direct impact on their professional practice.
Impact assessment of jockey helmet liner materials
Authors: McIntosh Andrew S , Patton Declan A , Thai Kim
Published: March 2012

Currently-available jockey helmets are typically assessed against performance standards which cater to equestrian helmets for all horse riding activities; however, severe impacts and head injuries in horse racing have become the focus of concern. The EN 14572 High Performance Helmets for Equestrian Activities Standard included a series of high energy impacts and other tests, such as lateral crush, that are not included in other equestrian helmet standards. Currently no helmet has been manufactured to meet this standard. This study assessed the energy attenuation performance of several materials that could be used to construct the inner liner of a jockey helmet designed to manage head acceleration to tolerable levels in high energy impacts. Among the materials assessed, it was found that dual-material samples performed better than single-material samples, with the combination of two polyurethane foams returning the lowest peak linear headform accelerations for higher drop heights. The results from this study compared well against the results of a similar study, with samples having better energy attenuation performance and smaller thicknesses. This study demonstrates the potential for new materials, and the layering of materials with different characteristics, to be considered for use in protective helmets.
Experience with radical perineal prostatectomy in the treatment of localized prostate cancer
Authors: Comploj Evi , Pycha Armin
Published: March 2012

Radical perineal prostatectomy is an alternative to the retropubic, robotic-assisted or the laparoscopic approach and it is one of the oldest surgical procedures for prostate cancer, but its use has declined over the past 30 years. The desire for lower morbidity, short hospital stay, and decreased costs has resulted in a renaissance of radical perineal prostatectomy. The combination of low morbidity, short hospital stay, and low economic costs brought to a renaissance of radical perineal prostatectomy.
Biologicals and bone loss
Authors: Krieckaert Charlotte L.M. , Lems Willem F.
Published: March 2012

Inflammatory joint diseases are associated with extra-articular side effects including bone involvement.There is an increased risk of osteoporotic fractures. The pathogeneses of local and generalized bone loss share a common pathway. Early and active rheumatoid arthritis is associated with longitudinal observed bone loss and fracture rate is of vertebral and nonvertebral fractures is doubled compared with matched healthy controls. Lowering disease activity with TNF inhibitors or is associated with stabilisation of bone mineral density by counteracting elevated bone resorption.
Basic opioid pharmacology: an update
Authors: Pathan Hasan , Williams John
Published: March 2012

Opioids are a group of analgesic agents commonly used in clinical practice. There are three classical opioid receptors (DOP, KOP and MOP), while the novel NOP receptor is considered to be a non-opioid branch of the opioid receptor family. Opioids can act at these receptors as agonists, antagonists or partial agonists. Opioid agonists bind to G-protein coupled receptors to cause cellular hyperpolarisation. Most clinically relevant opioid analgesics bind to MOP receptors in the central and peripheral nervous system in an agonist manner to elicit analgesia. Opioids may also be classified according to their mode of synthesis into alkaloids, semi-synthetic and synthetic compounds.
Mutation of the receptor tyrosine phosphatase PTPRC (CD45) in T-cell acute lymphoblastic leukemia
Authors: Porcu Michaël , Kleppe Maria , Gianfelici Valentina , Geerdens Ellen , De Keersmaecker Kim , Tartaglia Marco , Foà Robin , Soulier Jean , Cauwelier Barbara , Uyttebroeck Anne , Macintyre Elizabeth , Vandenberghe Peter , Asnafi Vahid , Cools Jan
Published: March 2012

The protein tyrosine phosphatase CD45, encoded by the PTPRC gene, is well known as a regulator of B- and T-cell receptor signaling. In addition, CD45 negatively regulates JAK family kinases downstream of cytokine receptors. Here, we report the presence of CD45 inactivating mutations in T-cell acute lymphoblastic leukemia. Loss-of-function mutations of CD45 were detected in combination with activating mutations in IL-7R, JAK1, or LCK, and down-regulation of CD45 expression caused increased signaling downstream of these oncoproteins. Furthermore, we demonstrate that down-regulation of CD45 expression sensitizes T cells to cytokine stimulation, as observed by increased JAK/STAT signaling, whereas overexpression of CD45 decreases cytokine-induced signaling. Taken together, our data identify a tumor suppressor role for CD45 in T-cell acute lymphoblastic leukemia.
PKC-δ mediates interferon-α-induced apoptosis through c-Jun NH2-terminal kinase activation
Authors: Yanase Noriko , Hayashida Miho , Kanetaka-Naka Yuki , Hoshika Akinori , Mizuguchi Junichiro
Published: March 2012

Background

Interferon-α (IFN-α) exerts an anti-tumor effect at least through induction of apoptosis in a variety of types including B lymphoma cells. We recently found that IFN-α induced a sustained activation of c-Jun NH2-terminal kinase1 (JNK1), which is implicated in activation of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) promoter. In the present study, we explored upstream component(s) of the prolonged IFN-α-initiated activation of JNK1.

Results

IFN-α caused activation of PKC-δ in Daudi B lymphoma cells and myeloma U266 cells, as detected by Western blotting using a monoclonal antibody specific for the phosphorylated form of PKC-δ. The dominant-negative form of mutant PKC-δ (dnPKC-δ) reduced the IFN-α-induced JNK1 activation, TRAIL promoter activity, loss of mitochondrial membrane potential (ΔΨm), and increase in propidium iodide (PI) positive cells. The IFN-α-induced activation of JNK1 and the TRAIL promoter was also attenuated by the PKC-δ inhibitor rottlerin. Moreover, a constitutively active form of mutant PKC-δ enhanced the IFN-α-induced TRAIL promoter activity and loss of ΔΨm in Daudi B lymphoma cells. In addition, IFN-α-induced Ser727 phosphorylation of Stat1 was also abrogated by dnPKC-δ.

Conclusions

IFN-α induced JNK1 activation via PKC-δ, leading to upregulation of TRAIL. The interaction of the consequent enhanced TRAIL expression with TRAIL-receptor results in a loss of ΔΨm and increase in PI positive cells. The IFN-α-induced apoptotic events may also be affected by the Ser727-Stat1 induced by PKC-δ-mediated signaling component(s).
Identification of genes expressed in cultures of E. coli lysogens carrying the Shiga toxin-encoding prophage Φ24B
Authors: Riley Laura M , Veses-Garcia Marta , Hillman Jeffrey D , Handfield Martin , McCarthy Alan J , Allison Heather E
Published: March 2012

Background

Shigatoxigenic E. coli are a global and emerging health concern. Shiga toxin, Stx, is encoded on the genome of temperate, lambdoid Stx phages. Genes essential for phage maintenance and replication are encoded on approximately 50% of the genome, while most of the remaining genes are of unknown function nor is it known if these annotated hypothetical genes are even expressed. It is hypothesized that many of the latter have been maintained due to positive selection pressure, and that some, expressed in the lysogen host, have a role in pathogenicity. This study used Change Mediated Antigen Technology (CMAT)™ and 2D-PAGE, in combination with RT-qPCR, to identify Stx phage genes that are expressed in E. coli during the lysogenic cycle.

Results

Lysogen cultures propagated for 5-6 hours produced a high cell density with a low proportion of spontaneous prophage induction events. The expression of 26 phage genes was detected in these cultures by differential 2D-PAGE of expressed proteins and CMAT. Detailed analyses of 10 of these genes revealed that three were unequivocally expressed in the lysogen, two expressed from a known lysogenic cycle promoter and one uncoupled from the phage regulatory network.

Conclusion

Propagation of a lysogen culture in which no cells at all are undergoing spontaneous lysis is impossible. To overcome this, RT-qPCR was used to determine gene expression profiles associated with the growth phase of lysogens. This enabled the definitive identification of three lambdoid Stx phage genes that are expressed in the lysogen and seven that are expressed during lysis. Conservation of these genes in this phage genome, and other Stx phages where they have been identified as present, indicates their importance in the phage/lysogen life cycle, with possible implications for the biology and pathogenicity of the bacterial host.
Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi
Authors: Ouyang Zhiming , Narasimhan Sukanya , Neelakanta Girish , Kumar Manish , Pal Utpal , Fikrig Erol , Norgard Michael V
Published: March 2012

Background

The maintenance of Borrelia burgdorferi in its complex tick-mammalian enzootic life cycle is dependent on the organism's adaptation to its diverse niches. To this end, the RpoN-RpoS regulatory pathway in B. burgdorferi plays a central role in microbial survival and Lyme disease pathogenesis by up- or down-regulating the expression of a number of virulence-associated outer membrane lipoproteins in response to key environmental stimuli. Whereas a number of studies have reported on the expression of RpoS and its target genes, a more comprehensive understanding of when activation of the RpoN-RpoS pathway occurs, and when induction of the pathway is most relevant to specific stage(s) in the life cycle of B. burgdorferi, has been lacking.

Results

Herein, we examined the expression of rpoS and key lipoprotein genes regulated by RpoS, including ospC, ospA, and dbpA, throughout the entire tick-mammal infectious cycle of B. burgdorferi. Our data revealed that transcription of rpoS, ospC, and dbpA is highly induced in nymphal ticks when taking a blood meal. The RpoN-RpoS pathway remains active during the mammalian infection phase, as indicated by the sustained transcription of rpoS and dbpA in B. burgdorferi within mouse tissues following borrelial dissemination. However, dbpA transcription levels in fed larvae and intermolt larvae suggested that an additional layer of control likely is involved in the expression of the dbpBA operon. Our results also provide further evidence for the downregulation of ospA expression during mammalian infection, and the repression of ospC at later phases of mammalian infection by B. burgdorferi.

Conclusion

Our study demonstrates that the RpoN-RpoS regulatory pathway is initially activated during the tick transmission of B. burgdorferi to its mammalian host, and is sustained during mammalian infection.
Acetylcholine content and viability of cholinergic neurons are influenced by the activity of protein histidine phosphatase
Authors: Eißing Anna , Fischer Daniel , Rauch Ilka , Baumann Anne , Schebb Nils-Helge , Karst Uwe , Rose Karsten , Klumpp Susanne , Krieglstein Josef
Published: March 2012

Background

The first mammalian protein histidine phosphatase (PHP) was discovered in the late 90s of the last century. One of the known substrates of PHP is ATP-citrate lyase (ACL), which is responsible - amongst other functions - for providing acetyl-CoA for acetylcholine synthesis in neuronal tissues. It has been shown in previous studies that PHP downregulates the activity of ACL by dephosphorylation. According to this our present work focused on the influence of PHP activity on the acetylcholine level in cholinergic neurons.

Results

The amount of PHP in SN56 cholinergic neuroblastoma cells was increased after overexpression of PHP by using pIRES2-AcGFP1-PHP as a vector. We demonstrated that PHP overexpression reduced the acetylcholine level and induced cell death. The acetylcholine content of SN56 cells was measured by fast liquid chromatography-tandem mass spectrometry method. Overexpression of the inactive H53A-PHP mutant also induced cell damage, but in a significantly reduced manner. However, this overexpression of the inactive PHP mutant did not change the acetylcholine content of SN56 cells significantly. In contrast, PHP downregulation, performed by RNAi-technique, did not induce cell death, but significantly increased the acetylcholine content in SN56 cells.

Conclusions

We could show for the first time that PHP downregulation increased the acetylcholine level in SN56 cells. This might be a potential therapeutic strategy for diseases involving cholinergic deficits like Alzheimer's disease.
KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study
Authors: Cerne Jasmina-Ziva , Stegel Vida , Gersak Ksenija , Novakovic Srdjan
Published: March 2012

Background

A single nucleotide polymorphism located in the 3'-untranslated region of the KRAS oncogene (KRAS variant; rs61764370) disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the KRAS variant with sporadic and familial breast cancer and breast tumor characteristics.

Methods

Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for BRCA1/2 mutations) and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT) use and tumor characteristics in sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the KRAS genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models.

Results

No evidence of association was observed between the KRAS variant and risk of sporadic and familial breast cancer - either among BRCA carriers or non-BRCA carriers. The KRAS variant was statistically significantly more often associated with human epidermal growth factor receptor 2 (HER2) - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users.

Conclusion

Our data do not support the hypothesis that the KRAS variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal women using HRT, the KRAS variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicators of a worse prognosis.
Prevalence of low back pain and associated occupational factors among Chinese coal miners
Authors: Xu Guangxing , Pang Dong , Liu Fengying , Pei Desheng , Wang Sheng , Li Liping
Published: March 2012

Background

Very few studies have evaluated the association between occupational factors and low back pain (LBP) among miners. The epidemiological data on LBP in Chinese miners are limited. The aim of this study was to measure the prevalence of low back pain in Chinese coal miners and to investigate the role of occupational factors.

Methods

A cross-sectional survey was conducted to examine 1573 coal miners in northern China. The prevalence of LBP over a 12-month period was assessed using the Nordic Musculoskeletal Questionnaire. Odds ratios were calculated to examine the association between the prevalence of LBP over a 12-month period and occupational factors using logistic regression.

Results

Among the coal miners, 64.9% self-reported LBP in a 12-month period. Occupational factors associated with LBP were identified, including tasks with a high degree of repetitiveness (OR 1.3, 95%CI 1.0-1.6), tasks characterized by a high level of physical demand (OR 1.4, 95% CI 1.1-1.8), posture requiring extreme bending (OR 1.6, 95% CI 1.2-1.7) and insufficient recovery time (OR 1.4, 95% CI 1.0-1.8).

Conclusion

Low back pain is common among Chinese miners. There were strong associations with occupational factors.
Lung function decline in relation to diagnostic criteria for airflow obstruction in respiratory symptomatic subjects
Authors: Akkermans Reinier P , Berrevoets Marvin A , Smeele Ivo J , Lucas Annelies E , Thoonen Bart P , Grootens-Stekelenburg Joke G , Heijdra Yvonne F , van Weel Chris , Schermer Tjard R
Published: March 2012

Background

Current COPD guidelines advocate a fixed < 0.70 FEV1/FVC cutpoint to define airflow obstruction. We compared rate of lung function decline in respiratory symptomatic 40+ subjects who were 'obstructive' or 'non-obstructive' according to the fixed and/or age and gender specific lower limit of normal (LLN) FEV1/FVC cutpoints.

Methods

We studied 3,324 respiratory symptomatic subjects referred to primary care diagnostic centres for spirometry. The cohort was subdivided into four categories based on presence or absence of obstruction according to the fixed and LLN FEV1/FVC cutpoints. Postbronchodilator FEV1 decline served as primary outcome to compare subjects between the respective categories.

Results

918 subjects were obstructive according to the fixed FEV1/FVC cutpoint; 389 (42%) of them were non-obstructive according to the LLN cutpoint. In smokers, postbronchodilator FEV1 decline was 21 (SE 3) ml/year in those non-obstructive according to both cutpoints, 21 (7) ml/year in those obstructive according to the fixed but not according to the LLN cutpoint, and 50 (5) ml/year in those obstructive according to both cutpoints (p = 0.004).

Conclusion

This study showed that respiratory symptomatic 40+ smokers and non-smokers who show FEV1/FVC values below the fixed 0.70 cutpoint but above their age/gender specific LLN value did not show accelerated FEV1 decline, in contrast with those showing FEV1/FVC values below their LLN cutpoint.
The National Adult Inpatient Survey conducted in the English National Health Service from 2002 to 2009: how have the data been used and what do we know as a result?
Authors: DeCourcy Anna , West Elizabeth , Barron David
Published: March 2012

Background

When it was initiated in 2001, England's national patient survey programme was one of the first in the world and has now been widely emulated in other healthcare systems. The aim of the survey programme was to make the National Health Service (NHS) more "patient centred" and more responsive to patient feedback. The national inpatient survey has now been running in England annually since 2002 gathering data from over 600,000 patients. The aim of this study is to investigate how the data have been used and to summarise what has been learned about patients' evaluation of care as a result.

Methods

Two independent researchers systematically gathered all research that included analyses of the English national adult inpatient survey data. Journals, databases and relevant websites were searched. Publications prior to 2002 were excluded. Articles were also identified following consultation with experts. All documents were then critically appraised by two co-authors both of whom have a background in statistical analysis.

Results

We found that the majority of the studies identified were reports produced by organisations contracted to gather the data or co-ordinate the data collection and used mainly descriptive statistics. A few articles used the survey data for evidence based reporting or linked the survey to other healthcare data. The patient's socio-demographic characteristics appeared to influence their evaluation of their care but characteristics of the workforce and the. At a national level, the results of the survey have been remarkably stable over time. Only in those areas where there have been co-ordinated government-led campaigns, targets and incentives, have improvements been shown. The main findings of the review are that while the survey data have been used for different purposes they seem to have incited little academic interest.

Conclusions

The national inpatient survey has been a useful resource for many authors and organisations but the full potential inherent in this large, longitudinal publicly available dataset about patients' experiences has not as yet been fully exploited.

This review suggests that the presence of survey results alone is not enough to improve patients' experiences and further research is required to understand whether and how the survey can be best used to improve standards of care in the NHS.
Differences in selective pressure on dhps and dhfr drug resistant mutations in western Kenya
Authors: McCollum Andrea M , Schneider Kristan A , Griffing Sean M , Zhou Zhiyong , Kariuki Simon , Ter-Kuile Feiko , Shi Ya Ping , Slutsker Laurence , Lal Altaf A , Udhayakumar Venkatachalam , Escalante Ananias A
Published: March 2012

Background

Understanding the origin and spread of mutations associated with drug resistance, especially in the context of combination therapy, will help guide strategies to halt and prevent the emergence of resistance. Unfortunately, studies have assessed these complex processes when resistance is already highly prevalent. Even further, information on the evolutionary dynamics leading to multidrug-resistant parasites is scattered and limited to areas with low or seasonal malaria transmission. This study describes the dynamics of strong selection for mutations conferring resistance against sulphadoxine-pyrimethamine (SP), a combination therapy, in western Kenya between 1992 and 1999, just before SP became first-line therapy (1999). Importantly, the study is based on longitudinal data, which allows for a comprehensive analysis that contrasts with previous cross-sectional studies carried out in other endemic regions.

Methods

This study used 236 blood samples collected between 1992 and 1999 in the Asembo Bay area of Kenya. Pyrosequencing was used to determine the alleles of dihydrofolate reductase (dhfr) and dihydropterote synthase (dhps) genes. Microsatellite alleles spanning 138 kb around dhfr and dhps, as well as, neutral markers spanning approximately 100 kb on chromosomes 2 and 3 were characterized.

Results

By 1992, the South-Asian dhfr triple mutant was already spreading, albeit in low frequency, in this holoendemic Kenyan population, prior to the use of SP as a first-line therapy. Additionally, dhfr triple mutant alleles that originated independently from the predominant Southeast Asian lineage were present in the sample set. Likewise, dhps double mutants were already present as early as 1992. There is evidence for soft selective sweeps of two dhfr mutant alleles and the possible emergence of a selective sweep of double mutant dhps alleles between 1992 and 1997. The longitudinal structure of the dataset allowed estimation of selection pressures on various dhfr and dhps mutants relative to each other based on a theoretical model tailored to P. falciparum. The data indicate that drug selection acted differently on the resistant alleles of dhfr and dhps, as evidenced by fitness differences. Thus a combination drug therapy such as SP, by itself, does not appear to select for "multidrug"-resistant parasites in areas with high recombination rate.

Conclusions

The complexity of these observations emphasizes the importance of population-based studies to evaluate the effects of strong drug selection on Plasmodium falciparum populations.
Genetic diversity in the block 2 region of the merozoite surface protein-1 of Plasmodium falciparum in central India
Authors: Bharti Praveen K , Shukla Man M , Sharma Yagya D , Singh Neeru
Published: March 2012

Background

Malaria continues to be a significant health problem in India. Several of the intended Plasmodium falciparum vaccine candidate antigens are highly polymorphic. The genetic diversity of P. falciparum merozoite surface protein-1 (MSP-1) has been extensively studied from various parts of the world. However, limited data are available from India. The aim of the present study was a molecular characterization of block 2 region of MSP-1 gene from the tribal-dominated, forested region of Madhya Pradesh.

Methods

DNA sequencing analysis was carried out in 71 field isolates collected between July 2005 to November 2005 and in 98 field isolates collected from July 2009 to December 2009. Alleles identified by DNA sequencing were aligned with the strain 3D7 and polymorphism analysis was done by using Edit Sequence tool (DNASTAR).

Results

The malaria positivity was 26% in 2005, which rose to 29% in 2009 and P. falciparum prevalence was also increased from 72% in 2005 to 81% in 2009. The overall allelic prevalence was higher in K1 (51%) followed by MAD20 (28%) and RO33 (21%) in 2005 while in 2009, RO33 was highest (40%) followed by K1 (36%) and MAD20 (24%).

Conclusions

The present study reports extensive genetic variations and dynamic evolution of block 2 region of MSP-1 in central India. Characterization of antigenic diversity in vaccine candidate antigens are valuable for future vaccine trials as well as understanding the population dynamics of P. falciparum parasites in this area.
Defining and detecting malaria epidemics in south-east Iran
Authors: McKelvie William R , Haghdoost Ali Akbar , Raeisi Ahmad
Published: March 2012

Background

A lack of consensus on how to define malaria epidemics has impeded the evaluation of early detection systems. This study aimed to develop local definitions of malaria epidemics in a known malarious area of Iran, and to use that definition to evaluate the validity of several epidemic alert thresholds.

Methods

Epidemic definition variables generated from surveillance data were plotted against weekly malaria counts to assess which most accurately labelled aberrations. Various alert thresholds were then generated from weekly counts or log counts. Finally, the best epidemic definition was used to calculate and compare sensitivities, specificities, detection delays, and areas under ROC curves of the alert thresholds.

Results

The best epidemic definition used a minimum duration of four weeks and week-specific and overall smoothed geometric means plus 1.0 standard deviation. It defined 13 epidemics. A modified C-SUM alert of untransformed weekly counts using a threshold of mean + 0.25 SD had the highest combined sensitivity and specificity. Untransformed C-SUM alerts also had the highest area under the ROC curve.

Conclusions

Defining local malaria epidemics using objective criteria facilitated the evaluation of alert thresholds. This approach needs further study to refine epidemic definitions and prospectively evaluate epidemic alerts.
Variation of chemical composition of essential oils in wild populations of Thymus algeriensis Boiss. et Reut., a North African endemic Species
Authors: Zouari Nacim , Ayadi Imen , Fakhfakh Nahed , Rebai Ahmed , Zouari Sami
Published: March 2012

Background

Thymus algeriensis is an endemic aromatic plant to Tunisia largely used in folk medicine and as a culinary herb. The bulks aromatic plants come from wild populations whose essential oils compositions as well as their biological properties are severely affected by the geographical location and the phase of the plant development. Therefore, the aim of the present work is to provide more information on the variation of essential oil composition of T. algeriensis collected during the vegetative and the flowering phases and from eight different geographical regions. Besides, influence of population location and phenological stage on yield and metal chelating activity of essential oils is also assessed.

Methods

The essential oil composition of Thymus algeriensis was determined mainly by GC/FID and GC/MS. The chemical differentiation among populations performed on all compounds was assessed by linear discriminate analysis and cluster analysis based on Euclidean distance.

Results

A total of 71 compounds, representing 88.99 to 99.76% of the total oil, were identified. A significant effect of the population location on the chemical composition variability of T. algeriensis oil was observed. Only 18 out of 71 compounds showed a statistically significant variation among population locations and phenological stages. Chemical differentiation among populations was high. Minor compounds play an important role to distinguish between chemical groups. Five chemotypes according to the major compounds have been distinguished. Chemotypes distribution is linked to the population location and not to bioclimate, indicating that local selective environmental factors acted on the chemotype diversity.

Conclusions

The major compounds at the species level were α-pinene (7.41-13.94%), 1,8-cineole (7.55-22.07%), cis-sabinene hydrate (0.10-12.95%), camphor (6.8-19.93%), 4-terpineol (1.55-11.86%), terpenyl acetate (0-14.92%) and viridiflorol (0-11.49%). Based on major compounds, the populations were represented by (α-pinene/1,8-cineole/cis-sabinene hydrate/camphor/viridiflorol), (1,8-cineole/camphor/terpenyl acetate), (α-pinene/1,8-cineole/camphor), (1,8-cineole/camphor/4-terpineol) and (α-pinene/1,8-cineole/cis-sabinene hydrate/camphor/4-terpineol) chemotypes. Variation of phenological stage did not have a statistically significant effect on the yield and metal chelating activity of the essential oil. These results can be used to investigate the geographical location and the harvesting time of this plant for relevant industries.
A tetravalent dengue nanoparticle stimulates antibody production in mice
Authors: Silva Elisângela F , Orsi Mariana , Andrade Ângela L , Domingues Rosana Z , Silva Breno M , de Araújo Helena RC , Pimenta Paulo FP , Diamond Michael S , Rocha Eliseu SO , Kroon Erna G , Malaquias Luiz CC , Coelho Luiz FL
Published: March 2012

Background

Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines.

Findings

Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested.

Conclusions

Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.
Rapamycin inhibition of baculovirus recombinant (BVr) ribosomal protein S6 kinase (S6K1) is mediated by an event other than phosphorylation
Authors: Beigh Mushtaq A , Showkat Mehvish , ul Hussain Mahboob , Latoo Shafat A , Majeed Sheikh T , Andrabi Khurshid I
Published: March 2012

Background

Ribosomal protein S6 kinase 1(S6K1) is an evolutionary conserved kinase that is activated in response to growth factors and viral stimuli to influence cellular growth and proliferation. This downstream effector of target of rapamycin (TOR) signaling cascade is known to be directly activated by TOR- kinase mediated hydrophobic motif (HM) phosphorylation at Threonine 412 (T412). Selective loss of this phosphorylation by inactivation of TOR kinase or activation/recruitment of a phosphatase has accordingly been implicated in mediating inhibition by rapamycin.

Findings

We present evidence that baculovirus driven expression of S6K1 in insect cells (Sf9) fails to activate the enzyme and instead renders it modestly active representing 4-6 folds less activity than its fully active mammalian counterpart. Contrary to the contention that viral infection activates TOR signaling pathway, we report that BVr enzyme fails to exhibit putative TOR dependent phosphorylation at the HM and the resultant phosphorylation at the activation loop (AL) of the enzyme, correlating with the level of activity observed. Surprisingly, the BVr enzyme continued to exhibit sensitivity to rapamycin that remained unaffected by mutations compromised for TOR phosphorylation (T412A) or deletions compromised for TOR binding (ΔNH 2-46/ΔCT104).

Conclusions

These data together with the ability of the BVr enzyme to resist inactivation by phosphatases indicate that inhibition by rapamycin is not mediated by any phosphorylation event in general and TOR dependent phosphorylation in particular.
Further evidence for the existence of major susceptibility of nasopharyngeal carcinoma in the region near HLA-A locus in Southern Chinese
Authors: Zhao Manli , Cai Hongbing , Li Xin , Zheng Hang , Yang Xuexi , Fang Weiyi , Zhang Longcheng , Wei Ganguan , Li Ming , Yao Kaitai , Li Xin
Published: March 2012

Background

Nasopharyngeal carcinoma (NPC) is a multi-factorial malignancy closely associated with environmental factors, genetic factors and Epstein-Barr virus infection. Human leukocyte antigen (HLA) complex, specially the region near HLA-A locus, was regarded as a major candidate region bearing NPC genetic susceptibility loci in many previous studies including two recent genome-wide association (GWA) studies. To provide further evidence for the NPC susceptibility in the region near HLA-A locus based on other previous studies, we carried out a two-stage hospital-based case control association study including 535 sporadic NPC patients and 525 cancer-free control subjects from Guangdong, a high prevalence area of NPC in China.

Methods

38 tag SNPs were initially selected by Heploview from the segment around HLA-A locus (from D6S211 to D6S510) and genotyped on GenomeLab SNPstream platform in 206 cases and 180 controls in the stage 1. Subsequently, the stage 1 significant SNPs and 17 additional SNPs were examined on another platform (Sequenom iPlex Assay) in another independent set of study population including 329 cases and 345 controls.

Results

Totally eight SNPs from the segment from D6S211 to D6S510 within HLA complex were found to be significantly associated with NPC. Two of the most significant SNPs (rs9260734 and rs2517716) located near to HLA-A and HCG9 respectively were in strong LD with some other SNPs of this region reported by two previous GWA studies. Meanwhile, Meanwhile, novel independent susceptibility loci (rs9404952, Pcombined = 6.6 × 10-5, OR combined = 1.45) was found to be close to HLA-G.

Conclusion

Therefore, our present study supports that the segment from D6S211 to D6S510 in HLA complex region might contain NPC susceptibility loci which indeed needs to be fully investigated in the future.
Synthesis and field emission properties of different ZnO nanostructure arrays
Authors: Fang Yaoguo , Wong Kin Mun , Lei Yong
Published: March 2012

In this article, zinc oxide (ZnO) nanostructures of different shapes were fabricated on silicon substrate. Well-aligned and long ZnO nanowire (NW) arrays, as well as leaf-like ZnO nanostructures (which consist of modulated and single-phase structures), were fabricated by a chemical vapor deposition (CVD) method without the assistance of a catalyst. On the other hand, needle-like ZnO NW arrays were first fabricated with the CVD process followed by chemical etching of the NW arrays. The use of chemical etching provides a low-cost and convenient method of obtaining the needle-like arrays. In addition, the field emission properties of the different ZnO NW arrays were also investigated where some differences in the turn-on field and the field-enhancement factors were observed for the ZnO nanostructures of different lengths and shapes. It was experimentally observed that the leaf-like ZnO nanostructure is most suitable for field emission due to its lowest turn-on and threshold field as well as its high field-enhancement factor among the different synthesized nanostructures.
Network coding-based multipath routing for energy efficiency in wireless sensor networks
Authors: Wang Lei , Yang Yuwang , Zhao Wei
Published: March 2012

This article studies the energy efficiency of wireless sensor networks with network coding-based multipath routing (NCMR). The employed multipath model is braided multipath model, and the network coding scheme is random linear network coding. Braided multiple paths to the sink node are established for each source node, and the packets encoded at source nodes are transmitted on the braided multipath network. Then, intermediate nodes re-encode the received packets and forward the new packets to next cluster. Finally, the sink node decodes the packets received from different paths and recovers the original data. When network coding is combined with multipath routing, the number of required routes and the total times of transmission in sensor networks are reduced, which leads energy consumption of NCMR lower than that of traditional multipath routing, and this is proved by the theoretical analysis results in this article. Meanwhile, results of the analysis show that NCMR provides more reliability. Extensive simulations are carried out, and the results are consistent with those of the theoretical analysis. Moreover, based on the study of the influence of different network parameters (e.g., number of hops, number of paths) on the performance of sensor networks, an optimal combination scheme of different parameters are proposed, which makes the network accomplish transmissions with less resource. Finally, in order to study the robustness of NCMR, some simulation experiments are carried out under special conditions such as interference on channels with memory, congested environments, and failed nodes, which show that NCMR is more effective in adapting to these scenarios.