bluuebunny/crossref_metadata_2025 huggingface dataset:
Fundamentalism and Bangladesh
Authors: Hussain Imtiaz
Published: July 2008

Even though the record-setting August 2005 explosion of over 500 bombs across Bangladesh killed only three people, the question if this is a new threat arena doomed to inflict even higher casualties cannot be escaped. Narrowing a generic discussion of fundamentalism, globalisation and terrorism to Bangladesh shows how five types and three levels of fundamentalism utilise globalised channels to bring terrorism closer. Distinguishing between mainstream and extremist Islam, the study finds that while legitimate participation in political coalition making empowers Islamic parties, it also unwittingly opens doors to jihadis. Alienated by chaotic politics, as people increasingly seek religious reassurances, jihadi entrepreneurs even benefit from an opportunity: exploiting 250,000 Bihari and 300,000 Rohingya refugees languishing in Bangladesh, utilising Wahhabi money, for whatever the purpose. The case is made to absorb refugees to reduce the potential terrorist pool, and thereby give meaning to the impressive ongoing economic performance.
India's China Policy in the 1950s
Authors: Patil Sameer Suryakant
Published: July 2008

This article examines India's China policy in the 1950s with reference to the balance of power theory. Using the logic of internal and external balancing, this article investigates the policy that India followed to contain the China threat. I argue that since Prime Minister Jawaharlal Nehru failed to perceive the China threat, India's policy did not aim at balancing China. In substantiating this argument, I focus upon the perceptions of Nehru, the key Indian policy maker on China, and analyse how his perceptions influenced the actual policy on ground. Studying this period in the bilateral relationship is relevant even today as some of the key issues afflicting the relationship originated during the 1950s.
Banking Sector Openness and Economic Growth
Authors: Bayraktar Nihal , Wang Yan
Published: July 2008

Banking sector openness may directly increase growth by improving the quality of financial services and increasing funds available, or indirectly by improving the efficiency of financial intermediaries, both of which may reduce the cost of financing, in turn, increase capital accumulation and economic growth. The objective of this paper is to empirically reinvestigate these direct and indirect links, using a more advanced econometric technique (generalised method-of-moments [GMM] dynamic panel estimators). An illustrative model is presented to link financial market development with investment. The empirical results support the presence of direct and indirect links, thus encouraging countries planning to open their financial markets.
Financial Growth in India
Authors: Mahadeva M.
Published: July 2008

Ever since the enactment of the Cooperative and Regional Rural Banks Acts and nationalisation of scheduled commercial banks, financial inclusion measures in India have led to physical expansion in the country. Unfortunately, the expansion has not brought about the necessary change in the backward and rural areas as financial services are yet to reach a vast majority of the population. The financial exclusion is characterised by limited service providers, limited goals and limited lending, besides a huge area of operation and missing linkages between financial institutions and local organisations. Demand-side factors have also contributed to the present dimension of financial exclusion, the result of which is that over two-thirds of the under-served segments resort to high-cost financial services from informal sources, which are present in every nook and corner. This paper considers a number of alternative initiatives to increase access to institutional financial services for the under-served population.
Us and Them
Authors: Gillispie Jesse , Chrispeels Janet H.
Published: July 2008

This article explores the conflict that emerged during the work of university researchers, education consultants, and district multishareholder teams engaged in a partnership for school reform. The authors draw on analysis of naturally occurring talk and other data collected over 2 years to explore the presence of conflict between a multishareholder team and a group of consultants during a 4-day learning lab. Investigation shows how discursive practices produce, reproduce, and transform the group over time, ultimately leading to the collaboration necessary for implementation of the reform plan. The authors elaborate on two main discursive practices: (a) the juxtaposing and problematizing of behavior, positioning participants' group membership in relation to the speaker, and (b) the use of certain pronouns. Analysis informs educational leaders working in multishareholder teams by illustrating discursive practices that might facilitate and hinder collaboration among different shareholders.
Changes in Family Life Perceived by Mothers of Young Adult TBI Survivors
Authors: Wongvatunyu Suporn , Porter Eileen J.
Published: July 2008

Little is known about changes in family life perceived by mothers of young adult survivors of a traumatic brain injury (TBI). A phenomenological method was used to describe the changes that seven mothers of TBI survivors perceived in family life 6 months or more after the TBI. The five basic changes in family life reported by mothers were: getting attention from each other for different reasons now, getting along with each other since the injury, facing new financial hurdles, going our separate ways down this new path, and splitting the family apart against our will. Compared to literature on stress and coping, the findings offered a unique perspective on changes in family life. Nurses can use the findings to initiate therapeutic conversations with mothers about changes in family life after a TBI.
Commentary on Buckner and Implications for Treatment Selection Among Foster Children With RAD
Authors: Chaffin Mark
Published: July 2008

This commentary discusses possible implications of Buckner's (2008) case study, which successfully applied behavioral parent training for a child in out-of-home care who was diagnosed with reactive attachment disorder (RAD). The report is discussed within the context of recommendations offered by the 2006 APSAC Task Force on Attachment Therapy, Reactive Attachment Disorder, and Attachment Problems. The discussion also address the question of how well brief evidence-based parenting models might be accepted by parents or clinicians who have presumed that traditional therapies do not work for children diagnosed with RAD or that radical and concerning treatments are required.
Naming Water
Authors: Sementelli Arthur Jay
Published: July 2008

Water management has increasingly become a hot button issue in the United States and worldwide. Access, use, and conservation issues continually emerge as societies grow and change. A key aspect of the debate revolves around what water “is.” Naming water as a mineral, as a public good, or as a commodity fundamentally changes its nature, shifting access among citizens, governments, and private firms. This essay discusses some of the issues, problems, and opportunities that emerge from these naming choices, while providing an overview of current water management practices.
Rail Security After 9/11
Authors: Johnston Van R. , Plant Jeremy F.
Published: July 2008

The terrorist attacks of September 11, 2001, raised serious questions about the security of the U.S. rail system. The rail freight industry has been largely deregulated since the 1980s and has been prospering, raising questions about how post-9/11 public policy might affect its ability to control its operations and at the same time ensure security against terrorist events. A response to the threat has been adopted by the private sector rail industry and the U.S. Department of Homeland Security that attempts to optimize and to implement a collaborative approach to regulation. Recent legislation is reviewed to show how this approach is now becoming the statutory basis for rail security.
Spectres of migration and the ghosts of Ellis Island
Authors: Maddern Jo Frances
Published: July 2008

This article is based on in-depth interviews carried out with producers involved in the restoration of Ellis Island Immigration Station, New York and those responsible for turning it into a successful national heritage site which opened to the public in 1990. The buildings on Ellis Island operated as an Immigration Station between approximately 1892 and 1924 during which time they processed over 16 million migrants of predominantly European origin. An analysis of interviews conducted as well as readings of Ellis Island taken from archives, folklore and US popular culture suggest that the site is imbued with the spectropolitics of its politically emotive immigrant processing past. Rather than dismissing the spectrality associated with Ellis Island as folkloric or irrational, the article attempts to untangle the different meanings attributed to the `ghosts' that circulate through the buildings and material objects that inhabit the island. It suggests that a number of `tropes' of ghostliness can be associated with the island; uncanny ghosts which defy the sanitizing force of the restoration; conjured ghosts, which are deliberately invoked by producers for various political and economic purposes, and the ghosts of deconstruction which make any meta-narrative of immigration history at Ellis Island a precarious if not troubling achievement.
cultural geographies essay: Indigenous spectrality and the politics of postcolonial ghost stories
Authors: Cameron Emilie
Published: July 2008

This essay considers the politics of describing Indigenous peoples as ghostly or haunting presences. Focusing on the history of haunting tropes in Canadian cultural production and the recent re-emergence of the spectral Indigenous figure in, among other places, a wilderness park in southwestern British Columbia, I argue that the mobilization of haunting tropes to make sense of contemporary settler-Indigenous relations reinscribes colonial power relations and fails to account for the specific experiences and claims of Indigenous peoples. At a time when cultural geographers are contemplating the possibilities of a `spectral turn', this essay asks what politics are involved in deploying a spectro-geographical approach to studies of the colonial and postcolonial.
Water-repellent Treatment on Military Uniform Fabrics: Physiological and Comfort Implications
Authors: Gibson Phil
Published: July 2008

Cost-effective nanotechnology-based water-repellent treatments for clothing fabrics are now commercially available. The effectiveness of these durable water repellent (DWR) fabric treatments are evaluated for application to military uniforms. The addition of a non-wicking finish to clothing fabric negatively impacts comfort in hot and humid environments. Clothing comfort may be improved by refining the DWR fabric treatment process to retain wicking properties on the fabrics inner surface.
Establishing Technically Adequate Measures of Progress in Early Numeracy
Authors: Lembke Erica S. , Foegen Anne , Whittaker Tiffany A. , Hampton David
Published: July 2008

The purpose of this study was to examine the use of three early numeracy measures to monitor the mathematics progress of students across time. One hundred and seven kindergarten and Grade 1 students were administered quantity discrimination, number identification, and missing-number measures once each month for 7 months. Alternate form reliability was adequate for instructional decision making, whereas criterion validity coefficients comparing the early numeracy measures to teacher judgment of student proficiency in mathematics and students' performance on a district-administered standardized test were lower than those observed in previous research. We used hierarchical linear modeling at each grade level to examine the ability of the three measures to model growth across time. All measures produced growth rates that were significant across time, for each grade level, with linear growth observed for the Number Identification measure only.
Implications of Recent Research
Authors: Christ Theodore J. , Scullin Sarah , Tolbize Anick , Jiban Cynthia L.
Published: July 2008

Curriculum-based measurement of mathematics (CBM-M) comprises a set of procedures and instrumentation to assess the level and trend of student achievement in early mathematics. The purpose of this article is to review the recent research and psychometric evidence for CBM-M. Although recent developments in CBM-M include procedures to assess early numeracy and application problems, this review focuses exclusively on computation assessment. The results of this review provide evidence that CBM-M is sufficiently reliable and valid for some applications; however, interpretation must be informed by the context and the scope of assessment domain. Mathematics computation is a subdomain of mathematics curriculum and assessment, and therefore, the validity of CBM-M is limited by its construct representation (i.e., stimulus set and task demands). Nevertheless, the review provides support for ongoing development and use of CBM-M as both a general outcome measure and subskill mastery measure for computation. Implications for research and practice are discussed.
XRD and NMR characterization of synthetic hectorites and the corresponding surfactant-exchanged clays
Authors: Gerstmans A. , Urbanczyk L. , Jérôme R. , Robert J.- L. , Grandjean J.
Published: July 2008

Synthetic hectorites and the corresponding surfactant-exchanged clays have been characterized by X-ray diffraction and 1H, 7Li, 13C, 23Na and 29Si solid-state nuclear magnetic resonance (NMR) spectroscopy. The low-charge clays retain water more efficiently, forming aggregates without extensive drying. The hydroxylated hectorite exhibits two 1H NMR signals near 0 ppm whereas the fluorohectorites are characterized by a single peak in the same region. The 23Na 2D 3Q magic angle spinning (MAS) spectra of the low-charge hectorites show a single peak. The 29Si NMR shift depends on the interlayer charge. Tactoids formed by the low-charge hectorites reduce the rate of surfactant incorporation. The population of the all-trans conformer of the hydrocarbon chain, determined by 13C MASNMR, varies with the surfactant content. 13C NMR relaxation data show an increase in mobility with the surfactant loading and along the long alkyl chain, from the polar head to the terminal group. Complexity of the motional behaviour precludes any detailed analysis. These modified clays are not useful in preparing poly(ε-caprolactone) nanocomposites by in situ polymerization.
Solubility and release of fenamates intercalated in layered double hydroxides
Authors: Del Arco M. , Fernández A. , Martín C. , Sayalero M. L. , Rives V.
Published: July 2008

The effect of a Mg- and Al-containing layered double hydroxide (LDH), used as an additive or as a matrix, on the dissolution and solubility of two non-steroidal anti-inflammatory drugs (NSAIDs), namely, mefenamic and meclofenamic acids, is reported. The use of MgAl-LDH enhances the solubility of mefenamic acid at the three pH values tested, and the value is larger when the acid is intercalated as opposed to simply being mixed with the layered material. For pure mefenamic acid, the most unfavourable pH is 1.2, while for the physical mixture and the sample with the intercalated drug, the most unfavourable pH is 4.5, for which the minimum increase in the amount of dissolved acid is recorded. The (dissolution) release-rate for both drugs when they are intercalated between the layers is much slower than for the physical mixture or for the dissolution of the pure drug.
Translational control of c-MYC by rapamycin promotes terminal myeloid differentiation
Authors: Wall Meaghan , Poortinga Gretchen , Hannan Katherine M. , Pearson Richard B. , Hannan Ross D. , McArthur Grant A.
Published: July 2008

c-MYC inhibits differentiation and regulates the process by which cells acquire biomass, cell growth. Down-regulation of c-MYC, reduced cell growth, and decreased activity of the PI3K/AKT/mTORC1 signal transduction pathway are features of the terminal differentiation of committed myeloid precursors to polymorphonuclear neutrophils. Since mTORC1 regulates growth, we hypothesized that pharmacological inhibition of mTORC1 by rapamycin may reverse the phenotypic effects of c-MYC. Here we show that granulocytes blocked in their ability to differentiate by enforced expression of c-MYC can be induced to differentiate by reducing exogenous c-MYC expression through rapamycin treatment. Rapamycin also reduced expression of endogenous c-MYC and resulted in enhanced retinoid-induced differentiation. Total cellular c-Myc mRNA and c-MYC protein stability were unchanged by rapamycin, however the amount of c-Myc mRNA associated with polysomes was reduced. Therefore rapamycin limited expression of c-MYC by inhibiting c-Myc mRNA translation. These findings suggest that mTORC1 could be targeted to promote terminal differentiation in myeloid malignancies characterized by dysregulated expression of c-MYC.
The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency
Authors: Wood Alice M , Simmonds Matthew J , Bayley Darren L , Newby Paul R , Gough Stephen C , Stockley Robert A
Published: July 2008

Background

Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies. This study investigated subjects with AATD to determine the relationship between specific phenotypes and TNFα polymorphisms.

Methods

424 unrelated subjects of the PiZZ genotype were assessed for history of chronic bronchitis, impairment of lung function and radiological presence of emphysema and bronchiectasis. A subset of subjects with 3 years consecutive lung function data was assessed for decline of lung function. Four single nucleotide polymorphisms (SNPs) tagging TNFα were genotyped using TaqMan® genotyping technologies and compared between subjects affected by each phenotype and those unaffected. Plasma TNFα levels were measured in all PiZZ subjects.

Results

All SNPs were in Hardy-Weinberg equilibrium. A significant difference in rs361525 genotype (p = 0.01) and allele (p = 0.01) frequency was seen between subjects with and without chronic bronchitis, independent of the presence of other phenotypes. TNFα plasma level showed no phenotypic or genotypic associations.

Conclusion

Variation in TNFα is associated with chronic bronchitis in AATD.
Protein evolution of ANTP and PRD homeobox genes
Authors: Fonseca Nuno A , Vieira Cristina P , Holland Peter WH , Vieira Jorge
Published: July 2008

Background

Although homeobox genes have been the subject of many studies, little is known about the main amino acid changes that occurred early in the evolution of genes belonging to different classes.

Results

In this study, we report a method for the fast and efficient retrieval of sequences belonging to the ANTP (HOXL and NKL) and PRD classes. Furthermore, we look for diagnostic amino acid residues that can be used to distinguish HOXL, NKL and PRD genes.

Conclusion

The reported protein features will facilitate the robust classification of homeobox genes from newly sequenced bilaterian genomes. Nevertheless, in non-bilaterian genomes our findings must be cautiously applied. In principle, as long as a good manually curated data set is available the approach here described can be applied to non-bilaterian organisms as well. Our results help focus experimental studies onto investigating the biochemical functions of key homeodomain residues in different gene classes.
The Hypocrea jecorina (Trichoderma reesei) hypercellulolytic mutant RUT C30 lacks a 85 kb (29 gene-encoding) region of the wild-type genome
Authors: Seidl Verena , Gamauf Christian , Druzhinina Irina S , Seiboth Bernhard , Hartl Lukas , Kubicek Christian P
Published: July 2008

Background

The hypercellulolytic mutant Hypocrea jecorina (anamorph Trichoderma reesei) RUT C30 is the H. jecorina strain most frequently used for cellulase fermentations and has also often been employed for basic research on cellulase regulation. This strain has been reported to contain a truncated carbon catabolite repressor gene cre1 and is consequently carbon catabolite derepressed. To date this and an additional frame-shift mutation in the glycoprotein-processing β-glucosidase II encoding gene are the only known genetic differences in strain RUT C30.

Results

In the present paper we show that H. jecorina RUT C30 lacks an 85 kb genomic fragment, and consequently misses additional 29 genes comprising transcription factors, enzymes of the primary metabolism and transport proteins. This loss is already present in the ancestor of RUT C30 – NG 14 – and seems to have occurred in a palindromic AT-rich repeat (PATRR) typically inducing chromosomal translocations, and is not linked to the cre1 locus. The mutation of the cre1 locus has specifically occurred in RUT C30. Some of the genes that are lacking in RUT C30 could be correlated with pronounced alterations in its phenotype, such as poor growth on α-linked oligo- and polyglucosides (loss of maltose permease), or disturbance of osmotic homeostasis.

Conclusion

Our data place a general caveat on the use of H. jecorina RUT C30 for further basic research.
Cross-platform comparison of SYBR® Green real-time PCR with TaqMan PCR, microarrays and other gene expression measurement technologies evaluated in the MicroArray Quality Control (MAQC) study
Authors: Arikawa Emi , Sun Yanyang , Wang Jie , Zhou Qiong , Ning Baitang , Dial Stacey L , Guo Lei , Yang Jingping
Published: July 2008

Background

The MicroArray Quality Control (MAQC) project evaluated the inter- and intra-platform reproducibility of seven microarray platforms and three quantitative gene expression assays in profiling the expression of two commercially available Reference RNA samples (
Nat Biotechnol
24:1115-22, 2006). The tested microarrays were the platforms from Affymetrix, Agilent Technologies, Applied Biosystems, GE Healthcare, Illumina, Eppendorf and the National Cancer Institute, and quantitative gene expression assays included TaqMan® Gene Expression PCR Assay, Standardized (Sta) RT-PCR™ and QuantiGene®. The data showed great consistency in gene expression measurements across different microarray platforms, different technologies and test sites. However, SYBR® Green real-time PCR, another common technique utilized by half of all real-time PCR users for gene expression measurement, was not addressed in the MAQC study. In the present study, we compared the performance of SYBR Green PCR with TaqMan PCR, microarrays and other quantitative technologies using the same two Reference RNA samples as the MAQC project. We assessed SYBR Green real-time PCR using commercially available RT2 Profiler™ PCR Arrays from SuperArray, containing primer pairs that have been experimentally validated to ensure gene-specificity and high amplification efficiency.

Results

The SYBR Green PCR Arrays exhibit good reproducibility among different users, PCR instruments and test sites. In addition, the SYBR Green PCR Arrays have the highest concordance with TaqMan PCR, and a high level of concordance with other quantitative methods and microarrays that were evaluated in this study in terms of fold-change correlation and overlap of lists of differentially expressed genes.

Conclusion

These data demonstrate that SYBR Green real-time PCR delivers highly comparable results in gene expression measurement with TaqMan PCR and other high-density microarrays.
Calcitonin gene-related peptide alters the firing rates of hypothalamic temperature sensitive and insensitive neurons
Authors: Braasch Daniel C , Deegan Erin M , Grimm Eleanor R , Griffin John D
Published: July 2008

Background

Transient hyperthermic shifts in body temperature have been linked to the endogenous hormone calcitonin gene-related peptide (CGRP), which can increase sympathetic activation and metabolic heat production. Recent studies have demonstrated that these centrally mediated responses may result from CGRP dependent changes in the activity of thermoregulatory neurons in the preoptic and anterior regions of the hypothalamus (POAH).

Results

Using a tissue slice preparation, we recorded the single-unit activity of POAH neurons from the adult male rat, in response to temperature and CGRP (10 μM). Based on the slope of firing rate as a function of temperature, neurons were classified as either warm sensitive or temperature insensitive. All warm sensitive neurons responded to CGRP with a significant decrease in firing rate. While CGRP did not alter the firing rates of some temperature insensitive neurons, responsive neurons showed an increase in firing rate.

Conclusion

With respect to current models of thermoregulatory control, these CGRP dependent changes in firing rate would result in hyperthermia. This suggests that both warm sensitive and temperature insensitive neurons in the POAH may play a role in producing this hyperthermic shift in temperature.
The usefulness of a new rapid diagnostic test, the First Response® Malaria Combo (pLDH/HRP2) card test, for malaria diagnosis in the forested belt of central India
Authors: Bharti Praveen K , Silawat Nipun , Singh Pushpendra P , Singh Mrigendra P , Shukla Manmohan , Chand Gyan , Dash Aditya P , Singh Neeru
Published: July 2008

Background

Malaria presents a diagnostic challenge in tribal belt of central India where two Plasmodium species, Plasmodium falciparum and Plasmodium vivax, are prevalent. In these areas, rapid detection of the malaria parasites and early treatment of infection remain the most important goals of disease management. Therefore, the usefulness of a new rapid diagnostic (RDT), the First Response® Combo Malaria Ag (pLDH/HRP2) card test was assessed for differential diagnosis between P. falciparum with other Plasmodium species in remote villages of Jabalpur district.

Methods

A finger prick blood sample was collected to prepare blood smear and for testing with the RDT after taking informed consent. The figures for sensitivity, specificity, accuracy and predictive values were calculated using microscopy as gold standard.

Results

Analysis revealed that overall, the RDT was 93% sensitive, 85% specific with a positive predictive value (PPV) of 79%, and a negative predictive value (NPV) of 95%. The accuracy 88% and J-index was 0.74. For P. falciparum, the sensitivity and specificity of the test were 96% and 95% respectively, with a PPV of 85% and a NPV of 99%. The RDT accuracy 95% and J-index was 0.84. For non-falciparum malaria, the sensitivity, specificity and accuracy were 83%, 94% and 92% respectively with a PPV of 69% and a NPV of 97%.

Conclusion

The RDTs are easy to use, reliable and simple to interpret. RDTs are more suited to health workers in situations where health services are deficient or absent. Therefore, the test can be used as an epidemiological tool for the rapid screening of malaria.
In-vitro antimycobacterial drug susceptibility testing of non-tubercular mycobacteria by tetrazolium microplate assay
Authors: Sankar Manimuthu Mani , Gopinath Krishnamoorthy , Singla Roopak , Singh Sarman
Published: July 2008

Background

Non-tubercular mycobacteria (NTM) has not been given due attention till the recent epidemic of HIV. This has led to increasing interest of health care workers in their biology, epidemiology and drug resistance. However, timely detection and drug susceptibility profiling of NTM isolates are always difficult in resource poor settings like India. Furthermore, no standardized methodology or guidelines are available to reproduce the results with clinical concordance.

Objective

To find an alternative and rapid method for performing the drug susceptibility assay in a resource limited settings like India, we intended to evaluate the utility of Tetrazolium microplate assay (TEMA) in comparison with proportion method for reporting the drug resistance in clinical isolates of NTM.

Methods

A total of fifty-five NTM isolates were tested for susceptibility against Streptomycin, Rifampicin, Ethambutol, Ciprofloxacin, Ofloxacin, Azithromycin, and Clarithromycin by TEMA and the results were compared with agar proportion method (APM).

Results

Of the 55 isolates, 23 (41.8%) were sensitive to all the drugs and the remaining 32 (58.2%) were resistant to at least one drug. TEMA had very good concordance with APM except with minor discrepancies. Susceptibility results were obtained in the median of 5 to 9 days by TEMA. The NTM isolates were highly sensitive against Ofloxacin (98.18% sensitive) and Ciprofloxacin (90.09% sensitive).M. mucogenicumwas sensitive only to Clarithromycin and resistant to all the other drugs tested. The concordance between TEMA and APM ranged between 96.4 – 100%.

Conclusion

Tetrazolium Microplate Assay is a rapid and highly reproducible method. However, it must be performed only in tertiary level Mycobacteriology laboratories with proper bio-safety conditions.
Distributed usability evaluation of the Pennsylvania Cancer Atlas
Authors: Bhowmick Tanuka , Robinson Anthony C , Gruver Adrienne , MacEachren Alan M , Lengerich Eugene J
Published: July 2008

Background

The Pennsylvania Cancer Atlas (PA-CA) is an interactive online atlas to help policy-makers, program managers, and epidemiologists with tasks related to cancer prevention and control. The PA-CA includes maps, graphs, tables, that are dynamically linked to support data exploration and decision-making with spatio-temporal cancer data. Our Atlas development process follows a user-centered design approach. To assess the usability of the initial versions of the PA-CA, we developed and applied a novel strategy for soliciting user feedback through multiple distributed focus groups and surveys. Our process of acquiring user feedback leverages an online web application (e-Delphi). In this paper we describe the PA-CA, detail how we have adapted e-Delphi web application to support usability and utility evaluation of the PA-CA, and present the results of our evaluation.

Results

We report results from four sets of users. Each group provided structured individual and group assessments of the PA-CA as well as input on the kinds of users and applications for which it is best suited. Overall reactions to the PA-CA are quite positive. Participants did, however, provide a range of useful suggestions. Key suggestions focused on improving interaction functions, enhancing methods of temporal analysis, addressing data issues, and providing additional data displays and help functions. These suggestions were incorporated in each design and implementation iteration for the PA-CA and used to inform a set of web-atlas design principles.

Conclusion

For the Atlas, we find that a design that utilizes linked map, graph, and table views is understandable to and perceived to be useful by the target audience of cancer prevention and control professionals. However, it is clear that considerable variation in experience using maps and graphics exists and for those with less experience, integrated tutorials and help features are needed. In relation to our usability assessment strategy, we find that our distributed, web-based method for soliciting user input is generally effective. Advantages include the ability to gather information from users distributed in time and space and the relative anonymity of the participants while disadvantages include less control over when and how often participants provide input and challenges for obtaining rich input.
Gene silencing by RNAi in mouse Sertoli cells
Authors: González-González Emilio , López-Casas Pedro P , del Mazo Jesús
Published: July 2008

Background

RNA interference (RNAi) is a valuable tool in the investigation of gene function. The purpose of this study was to examine the availability, target cell types and efficiency of RNAi in the mouse seminiferous epithelium.

Methods

The experimental model was based on transgenic mice expressing EGFP (enhanced green fluorescent protein). RNAi was induced by in vivo transfection of plasmid vectors encoding for short hairpin RNAs (shRNAs) targeting EGFP. shRNAs were transfected in vivo by microinjection into the seminiferous tubules via the rete testis followed by square wave electroporation. As a transfection reporter, expression of red fluorescent protein (HcRed 1) was used. Cell types, the efficiency of both transfections and RNAi were all evaluated.

Results

Sertoli cells were the main transfected cells. A reduction of about 40% in the level of EGFP protein was detected in cells successfully transfected both in vivo and in vitro. However, the efficiency of in vivo transfection was low.

Conclusion

In adult seminiferous epithelial cells, in vivo post-transcriptional gene silencing mediated by RNAi via shRNA is efficient in Sertoli cells. Similar levels of RNAi were detected both in vivo and in vitro. This also indicates that Sertoli cells have the necessary silencing machinery to repress the expression of endogenous genes via RNAi.
Persisting with prevention: The importance of adherence for HIV prevention
Authors: Weiss Helen A , Wasserheit Judith N , Barnabas Ruanne V , Hayes Richard J , Abu-Raddad Laith J
Published: July 2008

Background

Only four out of 31 completed randomized controlled trials (RCTs) of HIV prevention strategies against sexual transmission have shown significant efficacy. Poor adherence may have contributed to the lack of effect in some of these trials. In this paper we explore the impact of various levels of adherence on measured efficacy within an RCT.

Analysis

We used simple quantitative methods to illustrate the impact of various levels of adherence on measured efficacy by assuming a uniform population in terms of sexual behavior and the binomial model for the transmission probability per partnership.

At 100% adherence the measured efficacy within an RCT is a reasonable approximation of the true biological efficacy. However, as adherence levels fall, the efficacy measured within a trial substantially under-estimates the true biological efficacy. For example, at 60% adherence, the measured efficacy can be less than half of the true biological efficacy.

Conclusion

Poor adherence during a trial can substantially reduce the power to detect an effect, and improved methods of achieving and maintaining high adherence within trials are needed. There are currently 12 ongoing HIV prevention trials, all but one of which require ongoing user-adherence. Attention must be given to methods of maximizing adherence when piloting and designing RCTs and HIV prevention programmes.
Low-intensity pulsed ultrasound activates the phosphatidylinositol 3 kinase/Akt pathway and stimulates the growth of chondrocytes in three-dimensional cultures: a basic science study
Authors: Takeuchi Ryohei , Ryo Akihide , Komitsu Noriko , Mikuni-Takagaki Yuko , Fukui Atsuko , Takagi Yuta , Shiraishi Toshihiko , Morishita Shin , Yamazaki Yoshiyuki , Kumagai Ken , Aoki Ichiro , Saito Tomoyuki
Published: July 2008

Introduction

The effect of low-intensity pulsed ultrasound (LIPUS) on cell growth was examined in three-dimensional-cultured chondrocytes with a collagen sponge. To elucidate the mechanisms underlying the mechanical activation of chondrocytes, intracellular signaling pathways through the Ras/mitogen-activated protein kinase (MAPK) and the integrin/phosphatidylinositol 3 kinase (PI3K)/Akt pathways as well as proteins involved in proliferation of chondrocytes were examined in LIPUS-treated chondrocytes.

Methods

Articular cartilage tissue was obtained from the metatarso-phalangeal joints of freshly sacrificed pigs. Isolated chondrocytes mixed with collagen gel and culture medium composites were added to type-I collagen honeycomb sponges. Experimental cells were cultured with daily 20-minute exposures to LIPUS. The chondrocytes proliferated and a collagenous matrix was formed on the surface of the sponge. Cell counting, histological examinations, immunohistochemical analyses and western blotting analysis were performed.

Results

The rate of chondrocyte proliferation was slightly but significantly higher in the LIPUS group in comparison with the control group during the 2-week culture period. Western blot analysis showed intense staining of type-IX collagen, cyclin B1 and cyclin D1, phosphorylated focal adhesion kinase, and phosphorylated Akt in the LIPUS group in comparison with the control group. No differences were detected, however, in the MAPK, phosphorylated MAPK and type-II collagen levels.

Conclusion

LIPUS promoted the proliferation of cultured chondrocytes and the production of type-IX collagen in a three-dimensional culture using a collagen sponge. In addition, the anabolic LIPUS signal transduction to the nucleus via the integrin/phosphatidylinositol 3-OH kinase/Akt pathway rather than the integrin/MAPK pathway was generally associated with cell proliferation.
Phase II Multicenter Study of Bendamustine Plus Rituximab in Patients With Relapsed Indolent B-Cell and Mantle Cell Non-Hodgkin's Lymphoma
Authors: Robinson K. Sue , Williams Michael E. , van der Jagt Richard H. , Cohen Philip , Herst Jordan A. , Tulpule Anil , Schwartzberg Lee S. , Lemieux Bernard , Cheson Bruce D.
Published: July 2008

Purpose

Bendamustine HCl is a bifunctional mechlorethamine derivative with clinical activity in the treatment of non-Hodgkin's lymphoma. This study evaluated bendamustine plus rituximab in 67 adults with relapsed, indolent B-cell or mantle cell lymphoma without documented resistance to prior rituximab.

Patients and Methods

Patients received rituximab 375 mg/m2 intravenously on day 1 and bendamustine 90 mg/m2 intravenously on days 2 and 3 of each 28-day cycle for four to six cycles. An additional dose of rituximab was administered 1 week before the first cycle and 4 weeks after the last cycle. Sixty-six patients (median age, 60 years) received at least one dose of both drugs.

Results

Overall response rate was 92% (41% complete response, 14% unconfirmed complete response, and 38% partial response). Median duration of response was 21 months (95% CI, 18 to 24 months). Median progression-free survival time was 23 months (95% CI, 20 to 26 months). Outcomes were similar for patients with indolent or mantle cell histologies. The combination was generally well tolerated; the primary toxicity was myelosuppression (grade 3 or 4 neutropenia, 36%; grade 3 or 4 thrombocytopenia, 9%).

Conclusion

Bendamustine plus rituximab is an active combination in patients with relapsed indolent and mantle cell lymphoma.
Modulation of Osteoclastogenesis by Fatty Acids
Authors: Cornish Jillian , MacGibbon Alastair , Lin Jian-Ming , Watson Maureen , Callon Karen E. , Tong P. C. , Dunford James E. , van der Does Yvonne , Williams Garry A. , Grey Andrew B. , Naot Dorit , Reid Ian R.
Published: July 2008

Clinical studies have shown that total body fat mass is related to both bone density and fracture risk and that fat ingestion reduces bone turnover. These effects are at least partially mediated by endocrine mechanisms, but it is possible that lipids might act directly on bone. We assessed the effects of broad fractions of milk lipids in osteoblasts, bone marrow, and neonatal mouse calvariae. Several milk fractions and their hydrolysates inhibited osteoclastogenesis in bone marrow cultures, so we assessed the effects of free fatty acids in this model. Saturated fatty acids (0.1–10 μg/ml) inhibited osteoclastogenesis in bone marrow cultures and RAW264.7 cells. This effect was maximal for C14:0 to C18:0 fatty acids. The introduction of greater than 1 double bond abrogated this effect; ω3 and ω6 fatty acids had comparable low activity. Osteoblast proliferation was modestly increased by the antiosteoclastogenic compounds, ruling out a nonspecific toxic effect. Active fatty acids did not consistently change expression of receptor activator of nuclear factor-κB ligand or osteoprotegerin in osteoblastic cells nor did they affect the activity of key enzymes in the mevalonate pathway. However, receptors known to bind fatty acids were found to be expressed in osteoblastic (GPR120) and osteoclastic (GPR40, 41, 43, 120) cells. A synthetic GPR 40/120 agonist mimicked the inhibitory effects of fatty acids on osteoclastogenesis. These findings provide a novel link between lipid and bone metabolism, which might contribute to the positive relationship between adiposity and bone density as well as provide novel targets for pharmaceutical and nutriceutical development.
Interleukin-1 Mediates the Anorexic and Febrile Actions of Galanin-Like Peptide
Authors: Man Pui-Sin , Lawrence Catherine B.
Published: July 2008

Galanin-like peptide (GALP) is a neuropeptide that has complex actions on energy balance, producing orexigenic effects in the short term in rats but anorexigenic and febrile effects over the longer term in rats and mice. GALP is thought to promote feeding via neuropeptide Y and orexin neurons, but the mediators of the anorexia are unknown. However, the anorexic and febrile actions of GALP are similar in magnitude and profile to those seen after central injections of the cytokine IL-1. Thus, the aim of this study was to test the hypothesis that IL-1 mediates the effects of GALP on energy balance. Intracerebroventricular injection of GALP (1.5 nmol) in male Sprague-Dawley rats stimulated production of IL-1α and IL-1β protein in macrophages and/or microglia in selected brain areas, including the meninges, and periventricular brain regions. Intracerebroventricular injection of GALP in rats stimulated food intake over 1 h but decreased feeding and body weight at 24 h and caused a rise in core body temperature over 8 h. Coinfusion of the IL-1 receptor antagonist had no effect on the GALP-induced orexigenic response but significantly reduced the longer-term actions of GALP observed at 24 h and its effect on body temperature. Furthermore, the actions of GALP on feeding, body weight, and body temperature were significantly reduced in IL-1α/β-, IL-1β-, or IL-1 type I receptor (IL-1RI)-deficient mice. These data suggest that GALP induces expression of IL-1 in the brain, and its anorexic and febrile actions are mediated by this cytokine acting via IL-1 type I receptor.
17β-Estradiol Activates Estrogen Receptor β-Signalling and Inhibits Transient Receptor Potential Vanilloid Receptor 1 Activation by Capsaicin in Adult Rat Nociceptor Neurons
Authors: Xu Shenghong , Cheng Ying , Keast Janet R. , Osborne Peregrine B.
Published: July 2008

There is mounting evidence that estrogens act directly on the nervous system to affect the severity of pain. Estrogen receptors (ERs) are expressed by sensory neurons, and in trigeminal ganglia, 17β-estradiol can indirectly enhance nociception by stimulating expression and release of prolactin, which increases phosphorylation of the nociceptor transducer transient receptor potential vanilloid receptor 1 (TRPV1). Here, we show that 17β-estradiol acts directly on dorsal root ganglion (DRG) sensory neurons to reduce TRPV1 activation by capsaicin. Capsaicin-induced cobalt uptake and the maximum TRPV1 current induced by capsaicin were inhibited when isolated cultured DRGs neurons from adult female rats were exposed to 17β-estradiol (10–100 nm) overnight. There was no effect of 17β-estradiol on capsaicin potency, TRPV1 activation by protons (pH 6–4), and P2X currents induced by α,β-methylene-ATP. Diarylpropionitrile (ERβ agonist) also inhibited capsaicin-induced TRPV1 currents, whereas propylpyrazole triol (ERα agonist) and 17α-estradiol (inactive analog) were inactive, and 17β-estradiol conjugated to BSA (membrane-impermeable agonist) caused a small increase. TRPV1 inhibition was antagonized by tamoxifen (1 μm), but ICI182870 (10 μm) was a potent agonist and mimicked 17β-estradiol. We conclude that TRPV1 in DRG sensory neurons can be inhibited by a nonclassical estrogen-signalling pathway that is downstream of intracellular ERβ. This affects the vanilloid binding site targeted by capsaicin but not the TRPV1 activation site targeted by protons. These actions could curtail the nociceptive transducer functions of TRPV1 and limit chemically induced nociceptor sensitization during inflammation. They are consistent with clinical reports that female pelvic pain can increase after reductions in circulating estrogens.
Amino Acid-Modified Calcitonin Immunization Induces Tumor Epitope-Specific Immunity in a Transgenic Mouse Model for Medullary Thyroid Carcinoma
Authors: Wuttke Margret , Papewalis Claudia , Meyer Yvonne , Kessler Caroline , Jacobs Benedikt , Willenberg Holger S. , Schinner Sven , Kouatchoua Christine , Baehring Thomas , Scherbaum Werner A. , Schott Matthias
Published: July 2008

Up to now, no relevant tumor antigen has been identified in medullary thyroid carcinoma (MTC). The aim of the present study was to prove the concept of an immunization with an amino acid-modified calcitonin (CT) for the treatment of MTC in a transgenic mouse model. Amino acid-modified (human) CT has been chosen for vaccination because of its higher binding affinity to the murine H2-Kb-MHC molecule. Mice were immunized over 6 months with monthly injections of amino acid-modified CT-pulsed dendritic cells. For enumeration of tumor epitope-specific CD8+ cytotoxic T cells, tetramer analyses were performed. CT peptide-treated mice revealed a mean 0.73 ± 0.45 and 0.91 ± 0.59% positive cells, depending on the two tetramers tested, whereas no increase was seen in control protein-immunized mice (0.08–0.12% tetramer-positive cells). Importantly, the subset of CT-specific CD8+ T cells also showed a high expression of interferon-γ. In line with these results, CT-immunized mice also showed an intratumor infiltration with CD8+ T lymphocytes. Importantly, we also found a diminished tumor outgrowth of −57% and a decrease of the serum CT levels (2.0 ± 0.1 pg/ml) compared with control protein-immunized Ret/Cal mice (3.0 ± 0.4 pg/ml). In summary, we show that amino acid-modified CT is recognized from the immune system leading to a specific antitumor immune response and a diminished tumor outgrowth in transgenic MTC mice. The results are of potential importance because they might be applicable to patients with metastatic spread of a MTC.
Nonclassical Mechanisms of Progesterone Action in the Brain: I. Protein Kinase C Activation in the Hypothalamus of Female Rats
Authors: Balasubramanian Bhuvana , Portillo Wendy , Reyna Andrea , Chen Jian Zhong , Moore Anthony N. , Dash Pramod K. , Mani Shaila K.
Published: July 2008

The modulation of gene regulation by progesterone (P) and its classical intracellular regulation by progestin receptors in the brain, resulting in alterations in physiology and behavior has been well studied. The mechanisms mediating the short latency effects of P are less well understood. Recent studies have revealed rapid nonclassical signaling action of P involving the activation of intracellular signaling pathways. We explored the involvement of protein kinase C (PKC) in P-induced rapid signaling in the ventromedial nucleus of the hypothalamus (VMN) and preoptic area (POA) of the rat brain. Both the Ca2+-independent (basal) PKC activity representing the activation of PKC by the in vivo treatments and the Ca+2-dependent (total) PKC activity assayed in the presence of exogenous cofactors in vitro were determined. A comparison of the two activities demonstrated the strength and temporal status of PKC regulation by steroid hormones in vivo. P treatment resulted in a rapid increase in basal PKC activity in the VMN but not the POA. Estradiol benzoate priming augmented P-initiated increase in PKC basal activity in both the VMN and POA. These increases were inhibited by intracerebroventricular administration of a PKC inhibitor administered 30 min prior to P. The total PKC activity remained unchanged demonstrating maximal PKC activation within 30 min in the VMN. In contrast, P regulation in the POA significantly attenuated total PKC activity ± estradiol benzoate priming. These rapid changes in P-initiated PKC activity were not due to changes in PKC protein levels or phosphorylation status.