bluuebunny/crossref_metadata_2025 huggingface dataset:
A `pad' sensor for measuring the moisture content of building materials
Authors: Davies M. , Ye Z.
Published: July 2009

A range of techniques are available to measure the moisture content of building fabrics. Indeed a thermal dual-probe has been successfully developed by the authors for measuring the moisture content of building fabrics in situ. However, the dual-probe technique has limitations due to the fact that two, small diameter, parallel holes must be drilled for inserting the dual-probe into the material to be measured. It is difficult to drill such holes accurately in many building envelops and thus, such a dual-probe may be most useful for relatively `soft' materials, such as aerated concrete. This paper describes the `proof of concept' of an innovation that surmounts this problem via the development of a `pad' sensor. Instead of the `traditional' dual-probe approach, the heater and temperature sensor are fixed to the surface of a thermally insulated block. The most important benefit of the pad sensor approach is that no holes are required to be drilled in the material of interest. The moisture content of the building envelops can be measured simply by placing the pad sensor against the wall surface. Extensive finite element modelling was carried out to design the pad sensor and a prototype built. Initial experimental work was then carried out to test the pad sensor — the measured moisture content obtained from the pad sensor was compared with the results of a series of gravimetric analyses. Encouraging agreement between the two methods was obtained.

Practical application: A thermal dual-probe has been successfully developed by the authors for measuring the moisture content of building fabrics in situ. However, the dual-probe technique has limitations due to the fact that two, small diameter, parallel holes must be drilled for inserting the dual-probe into the material to be measured. This paper describes an innovation that surmounts this problem via the development of a `pad' sensor. The moisture content of the building envelopes can be accurately measured simply by placing the pad sensor against the wall surface. The pad sensor offers a non-destructive method to measure the moisture content and thus is potentially attractive for applications where this issue is of importance e.g. monitoring the moisture content of historical buildings.
When Race Matters: Racially Stigmatized Others and Perceiving Race as a Biological Construction Affect Biracial People's Daily Well-Being
Authors: Sanchez Diana T. , Garcia Julie A.
Published: July 2009

Stigmatized group members experience greater well-being in the presence of similar others, which may be driven by the perception that similar others value their shared stigmatized identities (i.e., high public regard). Using experience sampling methodology, this hypothesis is tested with biracial people (29 Asian/White, 23 Black/ White, and 26 Latino/White biracial participants). This study proposes that the greater percentage of stigmatized similar others in one's daily context would predict greater daily well-being for biracial people through higher public regard, but only if biracial people believe that race has biological meaning. These findings add to a growing, but limited, literature on biracial individuals. These findings are situated within the broader literature on stigma and similar others, as well as new theories regarding the consequences of believing race has biological meaning.
Severe Fatigue and Depressive Symptoms in Lower-Income Urban Postpartum Women
Authors: Doering Runquist Jennifer J. , Morin Karen , Stetzer Frank C.
Published: July 2009

The purpose of this study was to identify whether severe postpartum fatigue at 1 and 3 months postpartum was associated with depressive symptomatology at 6 months in lower-income urban women. A convenience sample of 43 lower-income postpartum women completed the Modified Fatigue Symptoms Checklist and Edinburgh Postpartum Depression scale at 1, 3, and 6 months postpartum. Participants who were severely fatigued at both 1 and 3 months postpartum were significantly more likely to exhibit depressive symptomatology at 6 months. Fatigue and depressive symptoms were moderately to strongly correlated at 1 ( r = .68), 3 ( r = .74), and 6 ( r = .70) months postpartum ( p = .001). Severe fatigue and depressive symptomatology often co-exist for months after childbirth. Future research should examine whether interventions to targeting severe postpartum fatigue in lower-income urban women may also effectively reduce depressive symptoms.
Flame-retardant Polypropylene Composites based on Magnesium Hydroxide Modified by Phosphorous-containing Polymers
Authors: Dehong Chen  , Qiukai Zheng  , Feiyue Liu  , Kai Xu  , Mingcai Chen
Published: July 2009

A novel copolymer of α-phenylethenylphosphonic acid and styrene was successfully synthesized and used to prepare surface-modified magnesium hydroxide (MH). Flame-retardant polypropylene composites were fabricated by filling the above MH. The combustibility, mechanical properties, and thermal behaviors of the composites were characterized. The results demonstrate that the above properties are improved with the amount of modifier and the phosphonic acid group contents on the main chain of the copolymer. Through the microstructure and the fracture surface morphology of the composites analyzed by transmission electron microscope and scanning electron microscope, the above improvements are mostly attributed to the good dispersion of surface-modified filler and the strong adhesion between the filler and matrix.
Infusing Participants’ Voices Into Grounded Theory Research
Authors: Kennedy Brianna L.
Published: July 2009

This article augments the author’s grounded theory study of student and teacher interactions in alternative education classrooms by presenting poetic transcription as a way to portray the essences and experiences of the participants. The author builds on the experimental writing traditions of other researchers to embrace her own experiences as a classroom teacher in crafting the poems out of the participants’ words. In so doing, the author actively interacts with the texts to co-construct new meaning that elucidates research findings. Utilizing her position between the worlds of research and practice, the author crafts the poems to convey personalities, victories, and complexities involved in these classrooms. This application of the methodology of poetic transcription allows for a deeper understanding of students’ and teachers’ experiences in these schools.
Uniting the Tribes of Fluency to Form a Metacognitive Nation
Authors: Alter Adam L. , Oppenheimer Daniel M.
Published: July 2009

Processing fluency, or the subjective experience of ease with which people process information, reliably influences people’s judgments across a broad range of social dimensions. Experimenters have manipulated processing fluency using a vast array of techniques, which, despite their diversity, produce remarkably similar judgmental consequences. For example, people similarly judge stimuli that are semantically primed (conceptual fluency), visually clear (perceptual fluency), and phonologically simple (linguistic fluency) as more true than their less fluent counterparts. The authors offer the first comprehensive review of such mechanisms and their implications for judgment and decision making. Because every cognition falls along a continuum from effortless to demanding and generates a corresponding fluency experience, the authors argue that fluency is a ubiquitous metacognitive cue in reasoning and social judgment.
Student text-making as semiotic work
Authors: Mavers Diane
Published: July 2009

Semiotic work is principled engagement in the making of meaning. The semiotic work of school-based learning entails interpretation and expression framed by the curriculum and the social practices of the classroom, and realized multimodally in diverse pedagogic interactions and activities. Micro-examination of the relationship between a teacher's multimodally constituted framing of a task and students' responses in drawing and writing on individual dry-wipe whiteboards investigates the resources they selected in order to demonstrate their engagement, to make their texts suited to how they would be used, and to represent in ways apt to the subject area. These fleeting texts were just one realization of meaning among others in the semiotic flow of the lesson. Notwithstanding the speed of production and erasing soon after, the students' investment of semiotic work was principled. Taking their efforts seriously provides the ground for supporting them as they learn to make texts apt to different discourses and genres.
Physical Activity at Child Care Settings: Review and Research Recommendations
Authors: Ward Dianne S. , Vaughn Amber , McWilliams Christina , Hales Derek
Published: July 2009

Child care settings, such as nursery schools and preschools, provide important opportunities to increase physical activity in children aged 2 to 5 years. Because of the large numbers of children enrolled, physical activity interventions at child care facilities have the potential to reach many children at an age when behaviors are influenced more easily. To learn more about this possibility, the authors conducted a systematic review of the published literature for intervention studies conducted at organized child care settings that focused on increasing children’s physical activity levels. Although 8 databases were searched from their inception, only 9 studies were found that met inclusion criteria, all of which were published since 2003. Of these, 7 studies implemented some type of organized educational program or specific curricula, whereas 2 studies implemented environmental changes. Intervention length across studies varied from 2 days to 12 months. Five studies demonstrated a positive change in physical activity; however, the limited number of studies included and the range of research quality made it difficult to draw clear conclusions. A number of potential targets for increasing physical activity at child care settings were identified, including active opportunities, sedentary opportunities, physical environment, staff training and behavior, center policies, and outreach. All these areas seem to merit further investigation, and specific research questions for each are discussed.
The illicit firearms trade in North America
Authors: Cook Philip J. , Cukier Wendy , Krause Keith
Published: July 2009

Gun violence in North American is the subject of much speculation and debate, often based on limited or incomplete empirical evidence. We summarize the regulatory frameworks in Mexico, the United States and Canada, and provide statistics on gun misuse in these countries. Based on our analysis of publicly available information on sources of crime guns, we conclude that while the United States is a major supplier of illegal handguns to Canada and illegal firearms of all types to Mexico, quantifying the extent of its role, particularly in Mexico, is difficult because of data limitations. Still more difficult is to project the consequences of an effective crackdown by US authorities. If the illicit supply from the USA dried up, the criminal gangs could turn to a variety of other sources that already appear to be playing some role. A complete analysis of these issues must await more complete disclosure by the authorities of data on gun sources and trafficking investigations.
Guns, crime and social order
Authors: Sheptycki James
Published: July 2009

Canada has undergone intensive public debate concerning firearms over the past two decades, much of which has concerned the effectiveness of gun control legislation. Since about 2005 public discourse has focused increasingly on an upsurge in gun-crime perpetrated by street-level criminals. The article examines the projection of these concerns within the Canadian mass media and through official statistics. It shows that gun control legislation appears to have had a positive effect on gun-related crime in Canada, but that a residuum of gun-crime has remained. Evidence suggests that a process of pistolization is ongoing in some places, but that it is not a dominant strain. The article also looks at some examples of grassroots resistance to pistolization in Canada in some communities that are worst affected by street-level gun crime.
The possible role of granzyme B in the pathogenesis of chronic obstructive pulmonary disease
Authors: Ngan David A. , Vickerman Shawna V. , Granville David J. , Man S. F. Paul , Sin Don D.
Published: July 2009

Chronic obstructive pulmonary disease (COPD) is a highly prevalent inflammatory lung condition characterized by airways disease and emphysema, and the precise mechanism of pathogenesis is poorly understood. The consistent features of COPD include protease-antiprotease imbalance, inflammation and accelerated aging caused by apoptosis or senescence. One family of molecules involved in all of these processes is the granzymes, serine proteases with the best-known member being granzyme B (GzmB). The majority of GzmB is released unidirectionally towards target cells, but GzmB can also be released nonspecifically and escape into the extracellular environment. GzmB is capable of cleaving extracellular matrix (ECM) proteins in vitro, and the accumulation of GzmB in the extracellular milieu during chronic inflammation in COPD could contribute to ECM degradation and remodelling and, consequently, the emphysematous phenotype in the lung. Preliminary studies suggest that increased GzmB expression is associated with increased COPD severity, and this may represent a promising new target for drug and biomarker discovery in COPD. In this paper, we review the potential pathogenic contributions of GzmB to the pathogenesis of COPD.
RUNX1 regulates phosphoinositide 3-kinase/AKT pathway: role in chemotherapy sensitivity in acute megakaryocytic leukemia
Authors: Edwards Holly , Xie Chengzhi , LaFiura Katherine M. , Dombkowski Alan A. , Buck Steven A. , Boerner Julie L. , Taub Jeffrey W. , Matherly Larry H. , Ge Yubin
Published: July 2009

RUNX1 (AML1) encodes the core binding factor α subunit of a heterodimeric transcription factor complex which plays critical roles in normal hematopoiesis. Translocations or down-regulation of RUNX1 have been linked to favorable clinical outcomes in acute leukemias, suggesting that RUNX1 may also play critical roles in chemotherapy responses in acute leukemias; however, the molecular mechanisms remain unclear. The median level of RUNX1b transcripts in Down syndrome (DS) children with acute megakaryocytic leukemia (AMkL) were 4.4-fold (P < .001) lower than that in non-DS AMkL cases. Short hairpin RNA knockdown of RUNX1 in a non-DS AMkL cell line, Meg-01, resulted in significantly increased sensitivity to cytosine arabinoside, accompanied by significantly decreased expression of PIK3CD, which encodes the δ catalytic subunit of the survival kinase, phosphoinositide 3 (PI3)–kinase. Transcriptional regulation of PIK3CD by RUNX1 was further confirmed by chromatin immunoprecipitation and promoter reporter gene assays. Further, a PI3-kinase inhibitor, LY294002, and cytosine arabinoside synergized in antileukemia effects on Meg-01 and primary pediatric AMkL cells. Our results suggest that RUNX1 may play a critical role in chemotherapy response in AMkL by regulating the PI3-kinase/Akt pathway. Thus, the treatment of AMkL may be improved by integrating PI3-kinase or Akt inhibitors into the chemotherapy of this disease.
A prospective study of serum soluble CD30 concentration and risk of non-Hodgkin lymphoma
Authors: Purdue Mark P. , Lan Qing , Martinez-Maza Otoniel , Oken Martin M. , Hocking William , Huang Wen-Yi , Baris Dalsu , Conde Betty , Rothman Nathaniel
Published: July 2009

Prediagnostic serum concentration of soluble CD30 (sCD30), a marker for chronic B-cell stimulation, has been associated with increased risk of developing AIDS-related non-Hodgkin lymphoma (NHL) in a recent study of HIV+ patients. To investigate among healthy persons whether serum sCD30 is associated with NHL risk, we carried out a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. There was a strong dose-response relationship between prediagnostic sCD30 concentration and NHL risk among 234 cases and 234 individually matched controls (odds ratio [95% confidence interval] for second, third, and fourth quartiles vs first quartile: 1.4 [0.8-2.6], 2.2 [1.2-4.1], 4.1 [2.2-7.8]; Ptrend < .001), which persisted among cases diagnosed 6 to 10 years after providing a blood sample. Given that a similar relationship has been observed among HIV+ patients, our findings suggest that chronic B-cell stimulation may be an important mechanism involved in B-cell lymphomagenesis among severely immunocompromised and healthy populations alike.
Functional redundancy of Ets1 and Ets2
Authors: Oettgen Peter
Published: July 2009

In this issue of Blood, Wei and colleagues investigate the overlapping roles of Ets1 and Ets2 in the regulation of endothelial cell function and survival during embryonic angiogenesis.1
How I treat ADA deficiency
Authors: Gaspar H. Bobby , Aiuti Alessandro , Porta Fulvio , Candotti Fabio , Hershfield Michael S. , Notarangelo Luigi D.
Published: July 2009

Adenosine deaminase deficiency is a disorder of purine metabolism leading to severe combined immunodeficiency (ADA-SCID). Without treatment, the condition is fatal and requires early intervention. Haematopoietic stem cell transplantation is the major treatment for ADA-SCID, although survival following different donor sources varies considerably. Unlike other SCID forms, 2 other options are available for ADA-SCID: enzyme replacement therapy (ERT) with pegylated bovine ADA, and autologous haematopoietic stem cell gene therapy (GT). Due to the rarity of the condition, the lack of large scale outcome studies, and availability of different treatments, guidance on treatment strategies is limited. We have reviewed the currently available evidence and together with our experience of managing this condition propose a consensus management strategy. Matched sibling donor transplants represent a successful treatment option with high survival rates and excellent immune recovery. Mismatched parental donor transplants have a poor survival outcome and should be avoided unless other treatments are unavailable. ERT and GT both show excellent survival, and therefore the choice between ERT, MUD transplant, or GT is difficult and dependent on several factors, including accessibility to the different modalities, response of patients to long-term ERT, and the attitudes of physicians and parents to the short- and potential long-term risks associated with different treatments.
CLEAN: CLustering Enrichment ANalysis
Authors: Freudenberg Johannes M , Joshi Vineet K , Hu Zhen , Medvedovic Mario
Published: July 2009

Background

Integration of biological knowledge encoded in various lists of functionally related genes has become one of the most important aspects of analyzing genome-wide functional genomics data. In the context of cluster analysis, functional coherence of clusters established through such analyses have been used to identify biologically meaningful clusters, compare clustering algorithms and identify biological pathways associated with the biological process under investigation.

Results

We developed a computational framework for analytically and visually integrating knowledge-based functional categories with the cluster analysis of genomics data. The framework is based on the simple, conceptually appealing, and biologically interpretable gene-specific functional coherence score (CLEAN score). The score is derived by correlating the clustering structure as a whole with functional categories of interest. We directly demonstrate that integrating biological knowledge in this way improves the reproducibility of conclusions derived from cluster analysis. The CLEAN score differentiates between the levels of functional coherence for genes within the same cluster based on their membership in enriched functional categories. We show that this aspect results in higher reproducibility across independent datasets and produces more informative genes for distinguishing different sample types than the scores based on the traditional cluster-wide analysis. We also demonstrate the utility of the CLEAN framework in comparing clusterings produced by different algorithms. CLEAN was implemented as an add-on R package and can be downloaded athttp://Clusteranalysis.org. The package integrates routines for calculating gene specific functional coherence scores and the open source interactive Java-based viewer Functional TreeView (FTreeView).

Conclusion

Our results indicate that using the gene-specific functional coherence score improves the reproducibility of the conclusions made about clusters of co-expressed genes over using the traditional cluster-wide scores. Using gene-specific coherence scores also simplifies the comparisons of clusterings produced by different clustering algorithms and provides a simple tool for selecting genes with a "functionally coherent" expression profile.
All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways
Authors: Lu Jianfeng , Tan Li , Li Ping , Gao Hui , Fang Bo , Ye Shoudong , Geng Zhe , Zheng Ping , Song Houyan
Published: July 2009

Background

All-trans retinoic acid (RA) is one of the most important morphogens with pleiotropic actions. Its embryonic distribution correlates with neural differentiation in the developing central nervous system. To explore the precise effects of RA on neural differentiation of mouse embryonic stem cells (ESCs), we detected expression of RA nuclear receptors and RA-metabolizing enzymes in mouse ESCs and investigated the roles of RA in adherent monolayer culture.

Results

Upon addition of RA, cell differentiation was directed rapidly and exclusively into the neural lineage. Conversely, pharmacological interference with RA signaling suppressed this neural differentiation. Inhibition of fibroblast growth factor (FGF) signaling did not suppress significantly neural differentiation in RA-treated cultures. Pharmacological interference with extracellular signal-regulated kinase (ERK) pathway or activation of Wnt pathway effectively blocked the RA-promoted neural specification. ERK phosphorylation was enhanced in RA-treated cultures at the early stage of differentiation.

Conclusion

RA can promote neural lineage entry by ESCs in adherent monolayer culture systems. This effect depends on RA signaling and its crosstalk with the ERK and Wnt pathways.
Differential expression of three galaxin-related genes during settlement and metamorphosis in the scleractinian coral Acropora millepora
Authors: Reyes-Bermudez Alejandro , Lin Zhiyi , Hayward David C , Miller David J , Ball Eldon E
Published: July 2009

Background

The coral skeleton consists of CaCO3deposited upon an organic matrix primarily as aragonite. Currently galaxin, fromGalaxea fascicularis, is the only soluble protein component of the organic matrix that has been characterized from a coral. Three genes related togalaxinwere identified in the coralAcropora millepora.

Results

One of theAcroporagenes (Amgalaxin) encodes a clear galaxin ortholog, while the others (Amgalaxin-like 1andAmgalaxin-like 2) encode larger and more divergent proteins. All three proteins are predicted to be extracellular and share common structural features, most notably the presence of repetitive motifs containing dicysteine residues. In situ hybridization reveals distinct, but partially overlapping, spatial expression of the genes in patterns consistent with distinct roles in calcification. Both of theAmgalaxin-likegenes are expressed exclusively in the early stages of calcification, whileAmgalaxincontinues to be expressed in the adult, consistent with the situation in the coralGalaxea.

Conclusion

Comparisons with molluscs suggest functional convergence in the two groups; lustrin A/pearlin proteins may be the mollusc counterparts of galaxin, whereas the galaxin-like proteins combine characteristics of two distinct proteins involved in mollusc calcification. Database searches indicate that, although sequences with high similarity to the galaxins are restricted to the Scleractinia, more divergent members of this protein family are present in other cnidarians and some other metazoans. We suggest that ancestral galaxins may have been secondarily recruited to roles in calcification in the Triassic, when the Scleractinia first appeared. Understanding the evolution of the broader galaxin family will require wider sampling and expression analysis in a range of cnidarians and other animals.
A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression
Authors: Mo Wen Juan , Fu Xu Ping , Han Xiao Tian , Yang Guang Yuan , Zhang Ji Gang , Guo Feng Hua , Huang Yan , Mao Yu Min , Li Yao , Xie Yi
Published: July 2009

Background

The identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression.

Results

In this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method). This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS) and Progression Score (PS) in progression analysis, True Positive Rate (TPR) in gene pair analysis, and Pathway Enrichment Score (PES) in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From this research, several gene interaction networks inferred could provide clues for the mechanism of prostate cancer progression.

Conclusion

The SIG method reliably identifies cancer progression correlated gene pairs, and performs well both in gene pair ontology analysis and in pathway enrichment analysis. This method provides an effective means of understanding the molecular mechanism of carcinogenesis by appropriately tracking down the process of cancer progression.
Unstable housing and hepatitis C incidence among injection drug users in a Canadian setting
Authors: Kim Christina , Kerr Thomas , Li Kathy , Zhang Ruth , Tyndall Mark W , Montaner Julio SG , Wood Evan
Published: July 2009

Background

There has emerged growing recognition of the link between housing and health. Since Vancouver, Canada has had increasing concerns with homelessness brought about by urban renewal in the lead-up to the 2010 Winter Olympic Games, we evaluated hepatitis C virus (HCV) incidence among injection drug users (IDU) with and without stable housing.

Methods

Data were derived from a collaboration between two prospective cohort studies of IDU in Vancouver, Canada. Using Cox Proportional Hazards regression, we compared HCV incidence among participants with and without stable housing, and determined independent predictors of HCV incidence.

Results

Overall, 3074 individuals were recruited between May 1996 and July 2007, among whom 2541 (82.7%) were baseline HCV-infected. Among the 533 (17.3%) individuals who were not HCV-infected at baseline, 147 tested HCV antibody-positive during follow-up, for an incidence density of 16.89 (95% confidence interval: 14.76 – 19.32) per 100 person-years. In a multivariate Cox regression model, unstable housing remained independently associated with HCV infection (relative hazard = 1.47 (1.02 – 2.13).

Conclusion

HCV prevalence and incidence are high in this setting and were associated with unstable housing. Efforts to protect existing low-income housing and improve access to housing may help to reduce HCV incidence.
A computational approach identifies two regions of Hepatitis C Virus E1 protein as interacting domains involved in viral fusion process
Authors: Bruni Roberto , Costantino Angela , Tritarelli Elena , Marcantonio Cinzia , Ciccozzi Massimo , Rapicetta Maria , El Sawaf Gamal , Giuliani Alessandro , Ciccaglione Anna Rita
Published: July 2009

Background

The E1 protein of Hepatitis C Virus (HCV) can be dissected into two distinct hydrophobic regions: a central domain containing an hypothetical fusion peptide (FP), and a C-terminal domain (CT) comprising two segments, a pre-anchor and a trans-membrane (TM) region. In the currently accepted model of the viral fusion process, the FP and the TM regions are considered to be closely juxtaposed in the post-fusion structure and their physical interaction cannot be excluded. In the present study, we took advantage of the natural sequence variability present among HCV strains to test, by purely sequence-based computational tools, the hypothesis that in this virus the fusion process involves the physical interaction of the FP and CT regions of E1.

Results

Two computational approaches were applied. The first one is based on the co-evolution paradigm of interacting peptides and consequently on the correlation between the distance matrices generated by the sequence alignment method applied to FP and CT primary structures, respectively. In spite of the relatively low random genetic drift between genotypes, co-evolution analysis of sequences from five HCV genotypes revealed a greater correlation between the FP and CT domains than respect to a control HCV sequence from Core protein, so giving a clear, albeit still inconclusive, support to the physical interaction hypothesis.

The second approach relies upon a non-linear signal analysis method widely used in protein science called Recurrence Quantification Analysis (RQA). This method allows for a direct comparison of domains for the presence of common hydrophobicity patterns, on which the physical interaction is based upon. RQA greatly strengthened the reliability of the hypothesis by the scoring of a lot of cross-recurrences between FP and CT peptides hydrophobicity patterning largely outnumbering chance expectations and pointing to putative interaction sites. Intriguingly, mutations in the CT region of E1, reducing the fusion process in vitro, strongly reduced the amount of cross-recurrence further supporting interaction between this region and FP.

Conclusion

Our results support a fusion model for HCV in which the FP and the C-terminal region of E1 are juxtaposed and interact in the post-fusion structure. These findings have general implications for viruses, as any visualization of the post-fusion FP-TM complex has been precluded by the impossibility to obtain crystallised viral fusion proteins containing the trans-membrane region. This limitation gives to sequence based modelling efforts a crucial role in the sketching of a molecular interpretation of the fusion process. Moreover, our data also have a more general relevance for cell biology as the mechanism of intracellular fusion showed remarkable similarities with viral fusion
Treatment of malaria from monotherapy to artemisinin-based combination therapy by health professionals in urban health facilities in Yaoundé, central province, Cameroon
Authors: Sayang Collins , Gausseres Mathieu , Vernazza-Licht Nicole , Malvy Denis , Bley Daniel , Millet Pascal
Published: July 2009

Background

After adoption of artesunate-amodiaquine (AS/AQ) as first-line therapy for the treatment of uncomplicated malaria by the malaria control programme, this study was designed to assess the availability of anti-malarial drugs, treatment practices and acceptability of the new protocol by health professionals, in the urban health facilities and drugstores of Yaoundé city, Cameroon.

Methods

Between April and August 2005, retrospective and current information was collected by consulting registers and interviewing health practitioners in urban health facilities using a structured questionnaire.

Results

In 2005, twenty-seven trade-named drugs have been identified in drugstores; quinine tablets (300 mg) were the most affordable anti-malarial drugs. Chloroquine was restricted to food market places and no generic artemisinin derivative was available in public health centres. In public health facilities, 13.6% of health professionals were informed about the new guidelines; 73.5% supported the use of AS-AQ as first-line therapy. However, 38.6% apprehended its use due to adverse events attributed to amodiaquine. Malaria treatment was mainly based on the diagnosis of fever. Quinine (300 mg tablets) was the most commonly prescribed first-line anti-malarial drug in adults (44.5%) and pregnant women (52.5%). Artequin®was the most cited artemsinin-based combination therapy (ACT) (9.9%). Medical sales representatives were the main sources of information on anti-malarials.

Conclusion

The use of AS/AQ was not implemented in 2005 in Yaoundé, despite the wide range of anti-malarials and trade-named artemisinin derivatives available. Nevertheless, medical practitioners will support the use of this combination, when it is available in a paediatric formulation, at an affordable price. Training, information and participation of health professionals in decision-making is one of the key elements to improve adherence to new protocol guidelines. This baseline information will be useful to monitor progress in ACT implementation in Cameroon.
Lipoprotein lipase expression, serum lipid and tissue lipid deposition in orally-administered glycyrrhizic acid-treated rats
Authors: Lim Wai Yen Alfred , Chia Yoke Yin , Liong Shih Yeen , Ton So Ha , Kadir Khalid Abdul , Syed Husain Sharifah Noor Akmal
Published: July 2009

Background

The metabolic syndrome (MetS) is a cluster of metabolic abnormalities comprising visceral obesity, dyslipidaemia and insulin resistance (IR). With the onset of IR, the expression of lipoprotein lipase (LPL), a key regulator of lipoprotein metabolism, is reduced. Increased activation of glucocorticoid receptors results in MetS symptoms and is thus speculated to have a role in the pathophysiology of the MetS. Glycyrrhizic acid (GA), the bioactive constituent of licorice roots (Glycyrrhiza glabra) inhibits 11β-hydroxysteroid dehydrogenase type 1 that catalyzes the activation of glucocorticoids. Thus, oral administration of GA is postulated to ameliorate the MetS.

Results

In this study, daily oral administration of 50 mg/kg of GA for one week led to significant increase in LPL expression in the quadriceps femoris (p < 0.05) but non-significant increase in the abdominal muscle, kidney, liver, heart and the subcutaneous and visceral adipose tissues (p > 0.05) of the GA-treated rats compared to the control. Decrease in adipocyte size (p > 0.05) in both the visceral and subcutaneous adipose tissue depots accompanies such selective induction of LPL expression. Consistent improvement in serum lipid parameters was also observed, with decrease in serum free fatty acid, triacylglycerol, total cholesterol and LDL-cholesterol but elevated HDL-cholesterol (p > 0.05). Histological analysis using tissue lipid staining with Oil Red O showed significant decrease in lipid deposition in the abdominal muscle and quadriceps femoris (p < 0.05) but non-significant decrease in the heart, kidney and liver (p > 0.05).

Conclusion

Results from this study may imply that GA could counteract the development of visceral obesity and improve dyslipidaemia via selective induction of tissue LPL expression and a positive shift in serum lipid parameters respectively, and retard the development of IR associated with tissue steatosis.
Harm reduction in hospitals: is it time?
Authors: Rachlis Beth S , Kerr Thomas , Montaner Julio SG , Wood Evan
Published: July 2009

Among persons who inject drugs (IDU), illicit drug use often occurs in hospitals and contributes to patient expulsion and/or high rates of leaving against medical advice (AMA) when withdrawal is inadequately managed. Resultant disruptions in medical care may increase the likelihood of several harms including drug resistance to antibiotics as well as costly readmissions and increased patient morbidity. In this context, there remains a clear need for the evaluation of harm reduction strategies versus abstinence-based strategies with respect to addressing ongoing issues related to substance use among addicted hospitalized patients. While hospitalization can be used to stabilize addicted patients as they recover from their acute illness and help them to achieve abstinence, patients unable to maintain abstinence should not be penalized for failing to do so at the expense of their health. This article describes harm reduction activities within hospitals and areas for future investigation.
Phase I/II open-label study of the biologic effects of the interleukin-2 immunocytokine EMD 273063 (hu14.18-IL2) in patients with metastatic malignant melanoma
Authors: Ribas Antoni , Kirkwood John M , Atkins Michael B , Whiteside Theresa L , Gooding William , Kovar Andreas , Gillies Stephen D , Kashala Oscar , Morse Michael A
Published: July 2009

Background

To explore the biological activity of EMD 273063 (hu14.18-IL2), a humanized anti-GD2 monoclonal antibody fused to interleukin-2 (IL2), in patients with unresectable, stage IV cutaneous melanoma as measured by induction of immune activation at the tumor site and in peripheral blood.

Methods

Nine patients were treated with 4 mg/m2per day of EMD 273063 given as a 4-h intravenous infusion on days 1, 2, and 3 every four weeks (one cycle). Peripheral blood was analyzed for T cell and natural killer cell phenotype and frequency, as well as levels of soluble IL2 receptor (sIL2R), IL10, IL6, tumor necrosis factor alpha and neopterin. Biopsies of tumor metastasis were performed prior to therapy and at day 10 of the first 2 cycles to study lymphocyte accumulation by immunohistochemistry.

Results

Treatment was generally well tolerated and there were no study drug-related grade 4 adverse events. Grade 3 events were mainly those associated with IL2, most commonly rigors (3 patients) and pyrexia (2 patients). Best response on therapy was stable disease in 2 patients. There were no objective tumor regressions by standard response criteria. Systemic immune activation was demonstrated by increases in serum levels of sIL2R, IL10, and neopterin. There was evidence of increased tumor infiltration by T cells, but not NK cells, in most post-dosing biopsies, suggesting recruitment of immune cells to the tumor site.

Conclusion

EMD 273063 demonstrated biologic activity with increased immune-related cytokines and intratumoral changes in some patients consistent with the suspected mechanism of action of this immunocytokine.
Clinical e valuation of magnetic resonance imaging in coronary heart disease: The CE-MARC study
Authors: Greenwood John P , Maredia Neil , Radjenovic Aleksandra , Brown Julia M , Nixon Jane , Farrin Amanda J , Dickinson Catherine , Younger John F , Ridgway John P , Sculpher Mark , Ball Stephen G , Plein Sven
Published: July 2009

Background

Several investigations are currently available to establish the diagnosis of coronary heart disease (CHD). Of these, cardiovascular magnetic resonance (CMR) offers the greatest information from a single test, allowing the assessment of myocardial function, perfusion, viability and coronary artery anatomy. However, data from large scale studies that prospectively evaluate the diagnostic accuracy of multi-parametric CMR for the detection of CHD in unselected populations are lacking, and there are few data on the performance of CMR compared with current diagnostic tests, its prognostic value and cost-effectiveness.

Methods/design

This is a prospective diagnostic accuracy cohort study of 750 patients referred to a cardiologist with suspected CHD. Exercise tolerance testing (ETT) will be preformed if patients are physically able. Recruited patients will then undergo CMR and single photon emission tomography (SPECT) followed in all patients by invasive X-ray coronary angiography. The order of the CMR and SPECT tests will be randomised. The CMR study will comprise rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement and whole-heart MR coronary angiography. SPECT will use a gated stress/rest protocol. The primary objective of the study is to determine the diagnostic accuracy of CMR in detecting significant coronary stenosis, as defined by X-ray coronary angiography. Secondary objectives include an assessment of the prognostic value of CMR imaging, a comparison of its diagnostic accuracy against SPECT and ETT, and an assessment of cost-effectiveness.

Discussion

The CE-MARC study is a prospective, diagnostic accuracy cohort study of 750 patients assessing the performance of a multi-parametric CMR study in detecting CHD using invasive X-ray coronary angiography as the reference standard and comparing it with ETT and SPECT.

Trial Registration

Current Controlled Trials ISRCTN77246133
Characteristic gene expression profiles in the progression from liver cirrhosis to carcinoma induced by diethylnitrosamine in a rat model
Authors: Liu Yue-Fang , Zha Bin-Shan , Zhang Hui-Lin , Zhu Xiao-Jing , Li Yu-Hua , Zhu Jin , Guan Xiao-Hong , Feng Zhen-Qing , Zhang Jian-Ping
Published: July 2009

Background

Liver cancr is a heterogeneous disease in terms of etiology, biologic and clinical behavior. Very little is known about how many genes concur at the molecular level of tumor development, progression and aggressiveness. To explore the key genes involved in the development of liver cancer, we established a rat model induced by diethylnitrosamine to investigate the gene expression profiles of liver tissues during the transition to cirrhosis and carcinoma.

Methods

A rat model of liver cancer induced by diethylnitrosamine was established. The cirrhotic tissue, the dysplasia nodules, the early cancerous nodules and the cancerous nodules from the rats with lung metastasis were chosen to compare with liver tissue of normal rats to investigate the differential expression genes between them. Affymetrix GeneChip Rat 230 2.0 arrays were used throughout. The real-time quantity PCR was used to verify the expression of some differential expression genes in tissues.

Results

The pathological changes that occurred in the livers of diethylnitrosamine-treated rats included non-specific injury, fibrosis and cirrhosis, dysplastic nodules, early cancerous nodules and metastasis. There are 349 upregulated and 345 downregulated genes sharing among the above chosen tissues when compared with liver tissue of normal rats. The deregulated genes play various roles in diverse processes such as metabolism, transport, cell proliferation, apoptosis, cell adhesion, angiogenesis and so on. Among which, 41 upregulated and 27 downregulated genes are associated with inflammatory response, immune response and oxidative stress. Twenty-four genes associated with glutathione metabolism majorly participating oxidative stress were deregulated in the development of liver cancer. There were 19 members belong to CYP450 family downregulated, except CYP2C40 upregulated.

Conclusion

In this study, we provide the global gene expression profiles during the development and progression of liver cancer in rats. The data obtained from the gene expression profiles will allow us to acquire insights into the molecular mechanisms of hepatocarcinogenesis and identify specific genes (or gene products) that can be used for early molecular diagnosis, risk analysis, prognosis prediction, and development of new therapies.
Complexity, cofactors, and the failure of AIDS policy in Africa
Authors: Stillwaggon Eileen
Published: July 2009

Global AIDS policy still treats HIV as an exceptional case, abstracting from the context in which infection occurs. Policy is based on a simplistic theory of HIV causation, and evaluated using outdated tools of health economics. Recent calls for a health systems strategy – preventing and treating HIV within a programme of comprehensive health care – have not yet influenced the silo approach of AIDS policy.

Evidence continues to accumulate, showing that multiple factors, such as malnutrition, malaria and helminthes, increase the risk of sexual and vertical transmission of HIV. Moreover, complementary interventions that reduce viral load, improve immune response, and interrupt pathways of transmission could increase the effectiveness of antiretroviral drugs and other tools of AIDS policy.

In health economics, the omission of estimates of increasing returns generated by disease or treatment synergies biases cost‐effectiveness analysis against multiple, yet inexpensive, interventions. Current tools of cost‐effectiveness analysis only identify local maxima in a complex landscape, and can play, at best, a marginal role in the epidemic, especially where it is already generalized.

Cost‐effectiveness analyses for HIV that are based on the wrong epidemiological model can generate Type III errors: we get precise answers to the wrong questions about how to intervene. To control the epidemic, AIDS policy needs to utilize an epidemiological model that reflects the interactions of biological as well as behavioural variables that determine the course of HIV epidemics around the world. Cost‐effectiveness analysis can benefit from using economic concepts of externalities and increasing returns to incorporate disease interactions and beneficial treatment spillovers for coinfections in HIV‐prevention policy.
Legionella pneumophilamultiplication is enhanced by chronic AMPK signalling in mitochondrially diseased Dictyostelium cells
Authors: Francione Lisa , Smith Paige K. , Accari Sandra L. , Taylor Philip E. , Bokko Paul B. , Bozzaro Salvatore , Beech Peter L. , Fisher Paul R.
Published: July 2009

Human patients with mitochondrial diseases are more susceptible to bacterial infections, particularly of the respiratory tract. To investigate the susceptibility of mitochondrially diseased cells to an intracellular bacterial respiratory pathogen, we exploited the advantages of Dictyostelium discoideum as an established model for mitochondrial disease and for Legionella pneumophila pathogenesis. Legionella infection of macrophages involves recruitment of mitochondria to the Legionella-containing phagosome. We confirm here that this also occurs in Dictyostelium and investigate the effect of mitochondrial dysfunction on host cell susceptibility to Legionella. In mitochondrially diseased Dictyostelium strains, the pathogen was taken up at normal rates, but it grew faster and reached counts that were twofold higher than in the wild-type host. We reported previously that other mitochondrial disease phenotypes for Dictyostelium are the result of the activity of an energy-sensing cellular alarm protein, AMP-activated protein kinase (AMPK). Here, we show that the increased ability of mitochondrially diseased cells to support Legionella proliferation is suppressed by antisense-inhibiting expression of the catalytic AMPKα subunit. Conversely, mitochondrial dysfunction is phenocopied, and intracellular Legionella growth is enhanced, by overexpressing an active form of AMPKα in otherwise normal cells. These results indicate that AMPK signalling in response to mitochondrial dysfunction enhances Legionella proliferation in host cells.