bluuebunny/crossref_metadata_2025 huggingface dataset:
A Crisis of What? Mortgage Credit Markets and the Social Policy of Promoting Homeownership in the United States and in Europe
Authors: Schelkle Waltraud
Published: January 2012

The crisis of 2007-09 was prefigured by bubbles in the housing and mortgage credit markets of major Organisation for Economic Co-operation and Development (OECD) countries. A comparison of the United States, the United Kingdom, and France reveals that, contrary to popular perception, the two European countries had a bigger housing price bubble, more volatility, and a more short-termist mortgage market. Yet, the fallout of the crisis—in terms of overindebtedness of mortgage holders, foreclosures of homes, and the extent to which the “nest-eggs” of households were devalued—has been worse in the United States. This article explores which differences in the use of credit markets for the social policy of promoting homeownership can account for this puzzling finding.
In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells
Authors: Vishnubalaji Radhakrishnan , Manikandan Muthurangan , Al-Nbaheen May , Kadalmani Balamuthu , Aldahmash Abdullah , Alajez Nehad M
Published: January 2012

Background

Multipotent stem cells have been successfully isolated from various tissues and are currently utilized for tissue-engineering and cell-based therapies. Among the many sources, skin has recently emerged as an attractive source for multipotent cells because of its abundance. Recent literature showed that skin stromal cells (SSCs) possess mesoderm lineage differentiation potential; however, the endothelial differentiation and angiogenic potential of SSC remains elusive. In our study, SSCs were isolated from human neonatal foreskin (hNFSSCs) and adult dermal skin (hADSSCs) using explants cultures and were compared with bone marrow (hMSC-TERT) and adipose tissue-derived mesenchymal stem cells (hADMSCs) for their potential differentiation into osteoblasts, adipocytes, and endothelial cells.

Results

Concordant with previous studies, both MSCs and SSCs showed similar morphology, surface protein expression, and were able to differentiate into osteoblasts and adipocytes. Using an endothelial induction culture system combined with an in vitro matrigel angiogenesis assay, hNFSSCs and hADSSCs exhibited the highest tube-forming capability, which was similar to those formed by human umbilical vein endothelial cells (HUVEC), with hNFSSCs forming the most tightly packed, longest, and largest diameter tubules among the three cell types. CD146 was highly expressed on hNFSSCs and HUVEC followed by hADSSCs, and hMSC-TERT, while its expression was almost absent on hADMSCs. Similarly, higher vascular density (based on the expression of CD31, CD34, vWF, CD146 and SMA) was observed in neonatal skin, followed by adult dermal skin and adipose tissue. Thus, our preliminary data indicated a plausible relationship between vascular densities, and the expression of CD146 on multipotent cells derived from those tissues.

Conclusions

Our data is the first to demonstrate that human dermal skin stromal cells can be differentiated into endothelial lineage. Hence, SSCs represents a novel source of stem/stromal cells for tissue regeneration and the vascularization of engineered tissues. Moreover, the CD146 investigations suggested that the microenvironmental niche might contribute to direct stromal cells multipotency toward certain lineages, which warrants further investigation.
Factors associated with utilization of long acting and permanent contraceptive methods among married women of reproductive age in Mekelle town, Tigray region, north Ethiopia
Authors: Alemayehu Mussie , Belachew Tefera , Tilahun Tizta
Published: January 2012

Background

Ethiopia is the second most populous country in Sub-Saharan Africa. Total Fertility Rate of Ethiopia is 5.4 children per women, population growth rate is estimated to be 2.7% per year and contraceptive prevalence rate is only 15% while the unmet need for family planning is 34%. Overall awareness of Family Planning methods is high, at 87%. The prevalence of long acting and permanent contraceptive methods (LAPMs) in Tigray region was very low which accounts for 0.1% for implants and no users for intra-uterine contraceptive device (IUCD) and female sterilization. Moreover almost all modern contraceptive use in Ethiopia is dependent on short acting contraceptive methods. The objective of this study was to assess factors associated with utilization of long acting and permanent contraceptive methods (LAPM) among married women of reproductive age group in Mekelle town.

Methods

A cross sectional community based survey was conducted from March 9-20, 2011. Multistage sample technique was used to select the participants for the quantitative methods whereas purposive sampling was used for the qualitative part of the study. Binary descriptive statistics and multiple variable regressions were done.

Results

The study consisted of quantitative and qualitative data. From the quantitative part of the study the response rate of the study was 95.6%. Of the qualitative part two FGDs were conducted for each married women and married men. 64% of the married women heard about LAPMs. More than half (53.6%) of the married women had negative attitude towards practicing of LAPMs. The overall prevalence of LAPMs use was 12.3% however; there were no users for female or male sterilization. The main reason cited by the majority of the married women for not using LAPMs was using another method of contraception 360 (93.3%). Mothers who had high knowledge were 8 times more likely to use LAPMs as compared with those who had low knowledge (AOR = 7.9, 95% CI of (3.1, 18.3). Mothers who had two or more pregnancies were 3 times more likely to use LAPM as compared with those who had one pregnancy (AOR = 2.7, 95% CI of (1.4, 5.1).

Conclusion

A significant amount of the participants had low knowledge on permanent contraceptive particularly vasectomy. More than half (53.6%) of married women had negative attitude towards practicing of LAMPs. Few of married women use female sterilization and none use of female sterilization and or vasectomy. Positive knowledge of LAMPs, women who had two and above pregnancies and women who do not want to have additional child were significantly associated. Information education communication should focus on alleviating factors hinder from practicing of LAPMs.
Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer
Authors: Mieog J Sven D , de Kruijf Esther M , Bastiaannet Esther , Kuppen Peter JK , Sajet Anita , de Craen Anton JM , Smit Vincent THBM , van de Velde Cornelis JH , Liefers Gerrit-Jan
Published: January 2012

Background

The purpose of this study was to compare the expression and the prognostic effect of the breast cancer stem cell marker aldehyde dehydrogenase-1 (ALDH1) in young and elderly breast cancer patients.

Methods

The study population (N = 574) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Median follow-up was 17.9 years (range: 0.1 to 23.5). Tissue microarray slides were immunohistochemically stained for ALDH1 expression and quantified by two independent observers who were blinded to clinical outcome. Assessment of the prognostic effect of ALDH1 expression was stratified according to age and systemic treatment.

Results

Complete lack of expression of ALDH1 was found in 40% of tumors. With increasing age more tumors showed complete absence of ALDH1 expression (P < .001). In patients aged > 65 years, ALDH1 status was not associated with any clinical outcome. Conversely, in patients aged < 65 years, ALDH1 positivity was an independent risk factor of worse outcome for relapse free period (hazard ratio = 1.71 (95% CI, 1.09 to 2.68); P = .021) and relative survival (relative excess risks of death = 2.36 (95% CI, 1.22 to 3.68); P = .016). Ten-year relative survival risk was 57% in ALDH1-positive patients compared to 83% in ALDH1-negative patients.

Conclusion

ALDH1 expression and its prognostic effect are age-dependent. Our results support the hypothesis that breast cancer biology is different in elderly patients compared to their younger counterparts and emphasizes the importance of taking into consideration age-specific interactions in breast cancer research.
Identification of a biomarker panel for colorectal cancer diagnosis
Authors: García-Bilbao Amaia , Armañanzas Rubén , Ispizua Ziortza , Calvo Begoña , Alonso-Varona Ana , Inza Iñaki , Larrañaga Pedro , López-Vivanco Guillermo , Suárez-Merino Blanca , Betanzos Mónica
Published: January 2012

Background

Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries.

Methods

A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60-mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables.

Results

After an exhaustive process of pre-processing to ensure data quality--lost values imputation, probes quality, data smoothing and intraclass variability filtering--the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples.

Conclusions

We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955).
Failure of a repeat course of cyclooxygenase inhibitor to close a PDA is a risk factor for developing chronic lung disease in ELBW infants
Authors: Adrouche-Amrani Lynda , Green Robert S , Gluck Karen M , Lin Jing
Published: January 2012

Background

The optimal treatment regimen or protocol for managing a persistent patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants has not been well established. This study was aimed at evaluating the failure rate of a cyclooxygenase (COX) inhibitor (COI) for PDA closure and to determine the incidence of a PDA requiring ligation in ELBW infants. We examined the clinical characteristics and risk factors that may predict the clinical consequences of failure of PDA closure by COI.

Methods

Medical information on 138 infants with birth weight (BW) < 1000 gm who survived for > 48 hours was retrieved. Clinical characteristics and outcomes of patients whose PDAs closed with COI were compared with those who did not close.

Results

Of the 138 patients, 112 survived to discharge. Eighty (71.4%) of those who survived received 1-3 courses of COI treatment for a symptomatic PDA. A total of 32 (40%) failed COI treatment and underwent PDA ligation. Multivariable logistic regression analysis suggests that the observed differences in the outcomes in infants with or without symptomatic PDA can be explained by the babies with symptomatic PDA being more immature and sicker. No significant difference was seen in the incidence of chronic lung disease (CLD) in infants whose PDA was treated medically versus those who failed medical treatment and then underwent ligation. However, after adjusting for disease severity and other known risk factors, the odds ratio of developing CLD for surviving babies with a persistent PDA compared to those whose PDA was successfully closed with 1-2 courses of COI is 3.24 (1.07-9.81; p = 0.038).

Conclusions

When successfully treated, PDA in ELBW infants did not contribute significantly to the adverse outcomes such as CLD, retinopathy of prematurity (ROP) and age at discharge. This suggests that it is beneficial for a hemodynamically significant PDA to be closed. The failure of a repeat course of COI to close a PDA is a major risk factor for developing CLD in ELBW infants.
A multilevel analysis of social capital and self-reported health: evidence from Seoul, South Korea
Authors: Han Sehee , Kim Heaseung , Lee Hee-Sun
Published: January 2012

Background

This study aims to resolve two limitations of previous studies. First, as only a few studies examining social capital have been conducted in non-western countries, it is inconclusive that the concept, which has been developed in Western societies, applies similarly to an Asian context. Second, this study considers social capital at the individual-level, area-level and cross-levels of interaction and examines its associations with health while simultaneously controlling for various confounders at both the individual-level and area-level, whereas previous studies only considered one of the two levels. The purpose of this study is therefore to examine the associations between social capital and health by using multilevel analysis after controlling for various confounders both at the individual and area-levels (i.e., concentrated disadvantage) in non-western countries.

Methods

We conducted a cross-sectional survey from December 2010 to April 2011 in Seoul, South Korea. The target population included respondents aged 25 years and older who have resided in the same administrative area since 2008. The final sample for this study consisted of 4,730 respondents within all 25 of Seoul's administrative areas.

Results

In our final model, individual-level social capital, including network sources (OR = 1.23; 95% CI = 1.11-1.37) and organizational participation (OR = 2.55; 95% CI = 2.11-3.08) was positively associated with good/very good health. Interestingly, the individual × area organizational participation cross-level interaction was negatively associated with good/very good health (OR = 0.40; 95% CI = 0.32-0.50), indicating that in areas with higher organizational participation, individuals with high organizational participation were less likely to report good/very good health when compared to low organizational participation individuals.

Conclusion

Our study provides evidence that individual-level social capital is associated with self-reported health, even after controlling for both individual and area-level confounders. Although this study did not find significant relationships between area-level organizational participation and self-reported health, this study found the cross-level interaction for social capital. Hence, in areas with lower organizational participation, the probability of reporting good/very good health is higher for individuals with high organizational participation than individuals with low organizational participation. This study, albeit tentatively, suggests that policy makers should focus upon social capital when making policies which aim to enhance one's health.
Antitumor activity of sorafenib-incorporated nanoparticles of dextran/poly(dl-lactide-co-glycolide) block copolymer
Authors: Kim Do Hyung , Kim Min-Dae , Choi Cheol-Woong , Chung Chung-Wook , Ha Seung Hee , Kim Cy Hyun , Shim Yong-Ho , Jeong Young-Il , Kang Dae Hwan
Published: January 2012

Sorafenib-incoporated nanoparticles were prepared using a block copolymer that is composed of dextran and poly(DL-lactide-co-glycolide) [Dexb LG] for antitumor drug delivery. Sorafenib-incorporated nanoparticles were prepared by a nanoprecipitation-dialysis method. Sorafenib-incorporated Dexb LG nanoparticles were uniformly distributed in an aqueous solution regardless of the content of sorafenib. Transmission electron microscopy of the sorafenib-incorporated Dexb LG nanoparticles revealed a spherical shape with a diameter < 300 nm. Sorafenib-incorporated Dexb LG nanoparticles at a polymer/drug weight ratio of 40:5 showed a relatively uniform size and morphology. Higher initial drug feeding was associated with increased drug content in nanoparticles and in nanoparticle size. A drug release study revealed a decreased drug release rate with increasing drug content. In an in vitro anti-proliferation assay using human cholangiocarcinoma cells, sorafenib-incorporated Dexb LG nanoparticles showed a similar antitumor activity as sorafenib. Sorafenib-incorporated Dexb LG nanoparticles are promising candidates as vehicles for antitumor drug targeting.
Global transgenerational gene expression dynamics in two newly synthesized allohexaploid wheat (Triticum aestivum) lines
Authors: Qi Bao , Huang Wei , Zhu Bo , Zhong Xiaofang , Guo Jianhua , Zhao Na , Xu Chunming , Zhang Huakun , Pang Jinsong , Han Fangpu , Liu Bao
Published: January 2012

Background

Alteration in gene expression resulting from allopolyploidization is a prominent feature in plants, but its spectrum and extent are not fully known. Common wheat (Triticum aestivum) was formed via allohexaploidization about 10,000 years ago, and became the most important crop plant. To gain further insights into the genome-wide transcriptional dynamics associated with the onset of common wheat formation, we conducted microarray-based genome-wide gene expression analysis on two newly synthesized allohexaploid wheat lines with chromosomal stability and a genome constitution analogous to that of the present-day common wheat.

Results

Multi-color GISH (genomic in situ hybridization) was used to identify individual plants from two nascent allohexaploid wheat lines between Triticum turgidum (2n = 4x = 28; genome BBAA) and Aegilops tauschii (2n = 2x = 14; genome DD), which had a stable chromosomal constitution analogous to that of common wheat (2n = 6x = 42; genome BBAADD). Genome-wide analysis of gene expression was performed for these allohexaploid lines along with their parental plants from T. turgidum and Ae. tauschii, using the Affymetrix Gene Chip Wheat Genome-Array. Comparison with the parental plants coupled with inclusion of empirical mid-parent values (MPVs) revealed that whereas the great majority of genes showed the expected parental additivity, two major patterns of alteration in gene expression in the allohexaploid lines were identified: parental dominance expression and non-additive expression. Genes involved in each of the two altered expression patterns could be classified into three distinct groups, stochastic, heritable and persistent, based on their transgenerational heritability and inter-line conservation. Strikingly, whereas both altered patterns of gene expression showed a propensity of inheritance, identity of the involved genes was highly stochastic, consistent with the involvement of diverse Gene Ontology (GO) terms. Nonetheless, those genes showing non-additive expression exhibited a significant enrichment for vesicle-function.

Conclusions

Our results show that two patterns of global alteration in gene expression are conditioned by allohexaploidization in wheat, that is, parental dominance expression and non-additive expression. Both altered patterns of gene expression but not the identity of the genes involved are likely to play functional roles in stabilization and establishment of the newly formed allohexaploid plants, and hence, relevant to speciation and evolution of T. aestivum.
Exacerbation of experimental autoimmune encephalomyelitis in prion protein (PrPc)-null mice: evidence for a critical role of the central nervous system
Authors: Gourdain Pauline , Ballerini Clara , Nicot Arnaud B , Carnaud Claude
Published: January 2012

Background

The cellular prion protein (PrPc) is a host-encoded glycoprotein whose transconformation into PrP scrapie (PrPSc) initiates prion diseases. The role of PrPc in health is still obscure, but many candidate functions have been attributed to the protein, both in the immune and the nervous systems. Recent data show that experimental autoimmune encephalomyelitis (EAE) is worsened in mice lacking PrPc. Disease exacerbation has been attributed to T cells that would differentiate into more aggressive effectors when deprived of PrPc. However, alternative interpretations such as reduced resistance of neurons to autoimmune insult and exacerbated gliosis leading to neuronal deficits were not considered.

Method

To better discriminate the contribution of immune cells versus neural cells, reciprocal bone marrow chimeras with differential expression of PrPc in the lymphoid or in the central nervous system (CNS) were generated. Mice were subsequently challenged with MOG35-55 peptide and clinical disease as well as histopathology were compared in both groups. Furthermore, to test directly the T cell hypothesis, we compared the encephalitogenicity of adoptively transferred PrPc-deficient versus PrPc-sufficient, anti-MOG T cells.

Results

First, EAE exacerbation in PrPc-deficient mice was confirmed. Irradiation exacerbated EAE in all the chimeras and controls, but disease was more severe in mice with a PrPc-deleted CNS and a normal immune system than in the reciprocal construction. Moreover, there was no indication that anti-MOG responses were different in PrPc-sufficient and PrPc-deficient mice. Paradoxically, PrPc-deficient anti-MOG 2D2 T cells were less pathogenic than PrPc-expressing 2D2 T cells.

Conclusions

In view of the present data, it can be concluded that the origin of EAE exacerbation in PrPc-ablated mice resides in the absence of the prion protein in the CNS. Furthermore, the absence of PrPc on both neural and immune cells does not synergize for disease worsening. These conclusions highlight the critical role of PrPc in maintaining the integrity of the CNS in situations of stress, especially during a neuroinflammatory insult.
The W100 pocket on HIV-1 gp120 penetrated by b12 is not a target for other CD4bs monoclonal antibodies
Authors: Dueñas-Decamp Maria J , O'Connell Olivia J , Corti Davide , Zolla-Pazner Susan , Clapham Paul R
Published: January 2012

Background

The conserved CD4 binding site (CD4bs) on HIV-1 gp120 is a major target for vaccines. It is a priority to determine sites and structures within the CD4bs that are important for inclusion in vaccines. We studied a gp120 pocket penetrated by W100 of the potent CD4bs monoclonal antibody (mab), b12. We compared HIV-1 envelopes and corresponding mutants that carried blocked W100 pockets to evaluate whether other CD4bs mabs target this site.

Findings

All CD4bs mabs tested blocked soluble CD4 binding to gp120 consistent with their designation as CD4bs directed antibodies. All CD4bs mabs tested neutralized pseudovirions carrying NL4.3 wild type (wt) envelope. However, only b12 failed to neutralize pseudoviruses carrying mutant envelopes with a blocked W100 pocket. In addition, for CD4bs mabs that neutralized pseudovirions carrying primary envelopes, mutation of the W100 pocket had little or no effect on neutralization sensitivity.

Conclusions

Our data indicate that the b12 W100 pocket on gp120 is infrequently targeted by CD4bs mabs. This site is therefore not a priority for preservation in vaccines aiming to elicit antibodies targeting the CD4bs.
Divergent lineage of a novel hantavirus in the banana pipistrelle (Neoromicia nanus) in Côte d'Ivoire
Authors: Sumibcay Laarni , Kadjo Blaise , Gu Se Hun , Kang Hae Ji , Lim Burton K , Cook Joseph A , Song Jin-Won , Yanagihara Richard
Published: January 2012

Recently identified hantaviruses harbored by shrews and moles (order Soricomorpha) suggest that other mammals having shared ancestry may serve as reservoirs. To investigate this possibility, archival tissues from 213 insectivorous bats (order Chiroptera) were analyzed for hantavirus RNA by RT-PCR. Following numerous failed attempts, hantavirus RNA was detected in ethanol-fixed liver tissue from two banana pipistrelles (Neoromicia nanus), captured near Mouyassué village in Côte d'Ivoire, West Africa, in June 2011. Phylogenetic analysis of partial L-segment sequences using maximum-likelihood and Bayesian methods revealed that the newfound hantavirus, designated Mouyassué virus (MOUV), was highly divergent and basal to all other rodent- and soricomorph-borne hantaviruses, except for Nova virus in the European common mole (Talpa europaea). Full genome sequencing of MOUV and further surveys of other bat species for hantaviruses, now underway, will provide critical insights into the evolution and diversification of hantaviruses.
Study of compartmentalization in the visna clinical form of small ruminant lentivirus infection in sheep
Authors: Ramírez Hugo , Reina Ramsés , Bertolotti Luigi , Cenoz Amaia , Hernández Mirna-Margarita , San Román Beatriz , Glaria Idoia , de Andrés Ximena , Crespo Helena , Jáuregui Paula , Benavides Julio , Polledo Laura , Pérez Valentín , García-Marín Juan F , Rosati Sergio , Amorena Beatriz , de Andrés Damián
Published: January 2012

Background

A central nervous system (CNS) disease outbreak caused by small ruminant lentiviruses (SRLV) has triggered interest in Spain due to the rapid onset of clinical signs and relevant production losses. In a previous study on this outbreak, the role of LTR in tropism was unclear and env encoded sequences, likely involved in tropism, were not investigated. This study aimed to analyze heterogeneity of SRLV Env regions - TM amino terminal and SU V4, C4 and V5 segments - in order to assess virus compartmentalization in CNS.

Results

Eight Visna (neurologically) affected sheep of the outbreak were used. Of the 350 clones obtained after PCR amplification, 142 corresponded to CNS samples (spinal cord and choroid plexus) and the remaining to mammary gland, blood cells, bronchoalveolar lavage cells and/or lung. The diversity of the env sequences from CNS was 11.1-16.1% between animals and 0.35-11.6% within each animal, except in one animal presenting two sequence types (30% diversity) in the CNS (one grouping with those of the outbreak), indicative of CNS virus sequence heterogeneity. Outbreak sequences were of genotype A, clustering per animal and compartmentalizing in the animal tissues. No CNS specific signature patterns were found.

Conclusions

Bayesian approach inferences suggested that proviruses from broncoalveolar lavage cells and peripheral blood mononuclear cells represented the common ancestors (infecting viruses) in the animal and that neuroinvasion in the outbreak involved microevolution after initial infection with an A-type strain. This study demonstrates virus compartmentalization in the CNS and other body tissues in sheep presenting the neurological form of SRLV infection.
The epidemiology and clinical correlates of HIV‐1 co‐receptor tropism in non‐subtype B infections from India, Uganda and South Africa
Authors: Ataher Quazi , Portsmouth Simon , Napolitano Laura A , Eng Sybil , Greenacre Anna , Kambugu Andrew , Wood Robin , Badal‐Faesen Sharlaa , Tressler Randy
Published: January 2012

Background

The introduction of C‐C chemokine receptor type‐5 (CCR5) antagonists as antiretroviral therapy has led to the need to study HIV co‐receptor tropism in different HIV‐1 subtypes and geographical locations. This study was undertaken to evaluate HIV‐1 co‐receptor tropism in the developing world where non‐B subtypes predominate, in order to assess the therapeutic and prophylactic potential of CCR5 antagonists in these regions.

Methods

HIV‐1‐infected patients were recruited into this prospective, cross‐sectional, epidemiologic study from HIV clinics in South Africa, Uganda and India. Patients were infected with subtypes C (South Africa, India) or A or D (Uganda). HIV‐1 subtype and co‐receptor tropism were determined and analyzed with disease characteristics, including viral load and CD4+ and CD8+ T cell counts.

Results

CCR5‐tropic (R5) HIV‐1 was detected in 96% of treatment‐naïve (TN) and treatment‐experienced (TE) patients in India, 71% of TE South African patients, and 86% (subtype A/A1) and 71% (subtype D) of TN and TE Ugandan patients. Dual/mixed‐tropic HIV‐1 was found in 4% of Indian, 25% of South African and 13% (subtype A/A1) and 29% (subtype D) of Ugandan patients. Prior antiretroviral treatment was associated with decreased R5 tropism; however, this decrease was less in subtype C from India (TE: 94%, TN: 97%) than in subtypes A (TE: 59%; TN: 91%) and D (TE: 30%; TN: 79%). R5 virus infection in all three subtypes correlated with higher CD4+ count.

Conclusions

R5 HIV‐1 was predominant in TN individuals with HIV‐1 subtypes C, A, and D and TE individuals with subtypes C and A. Higher CD4+ count correlated with R5 prevalence, while treatment experience was associated with increased non‐R5 infection in all subtypes.
Development and validation of 'AutoRIF': software for the automated analysis of radiation-induced foci
Authors: McVean Andrew , Kent Simon , Bakanov Alexei , Hobbs Tom , Anderson Rhona
Published: January 2012

Background

The quantification of radiation-induced foci (RIF) to investigate the induction and subsequent repair of DNA double strands breaks is now commonplace. Over the last decade systems specific for the automatic quantification of RIF have been developed for this purpose, however to ask more mechanistic questions on the spatio-temporal aspects of RIF, an automated RIF analysis platform that also quantifies RIF size/volume and relative three-dimensional (3D) distribution of RIF within individual nuclei, is required.

Results

A java-based image analysis system has been developed (AutoRIF) that quantifies the number, size/volume and relative nuclear locations of RIF within 3D nuclear volumes. Our approach identifies nuclei using the dynamic Otsu threshold and RIF by enhanced Laplacian filtering and maximum entropy thresholding steps and, has an application 'batch optimisation' process to ensure reproducible quantification of RIF. AutoRIF was validated by comparing output against manual quantification of the same 2D and 3D image stacks with results showing excellent concordance over a whole range of sample time points (and therefore range of total RIF/nucleus) after low-LET radiation exposure.

Conclusions

This high-throughput automated RIF analysis system generates data with greater depth of information and reproducibility than that which can be achieved manually and may contribute toward the standardisation of RIF analysis. In particular, AutoRIF is a powerful tool for studying spatio-temporal relationships of RIF using a range of DNA damage response markers and can be run independently of other software, enabling most personal computers to perform image analysis. Future considerations for AutoRIF will likely include more complex algorithms that enable multiplex analysis for increasing combinations of cellular markers.
Comprehensive analysis of published phase I/II clinical trials between 1990-2010 in osteosarcoma and Ewing sarcoma confirms limited outcomes and need for translational investment
Authors: van Maldegem Annemiek M , Bhosale Aparna , Gelderblom Hans J , Hogendoorn Pancras CW , Hassan Andrew B
Published: January 2012

Background

High grade primary bone sarcomas are rare cancers that affect mostly children and young adults. Osteosarcoma and Ewing sarcoma are the most common histological subtypes in this age group, with current multimodality treatment strategies achieving 55-70% overall survival. As there remains an urgent need to develop new therapeutic interventions, we have reviewed published phase I/II trials that have been reported for osteosarcoma and Ewing sarcoma in the last twenty years.

Results

We conducted a literature search for clinical trials between 1990 and 2010, either for trials enrolling bone sarcoma patients as part of a general sarcoma indication or trials specifically in osteosarcoma and Ewing sarcoma. We identified 42 clinical trials that fulfilled our search criteria for general sarcoma that enrolled these patient groups, and eight and twenty specific trials for Ewing and osteosarcoma patients, respectively. For the phase I trials which enrolled different tumour types our results were incomplete, because the sarcoma patients were not mentioned in the PubMed abstract. A total of 3,736 sarcoma patients were included in these trials over this period, 1,114 for osteosarcoma and 1,263 for Ewing sarcoma. As a proportion of the worldwide disease burden over this period, these numbers reflect a very small percentage of the potential patient recruitment, approximately 0.6% for Ewing sarcoma and 0.2% for osteosarcoma. However, these data show an increase in recent activity overall and suggest there is still much room for improvement in the current trial development structures.

Conclusion

Lack of resources and commercial investment will inevitably limit opportunity to develop sufficiently rapid improvements in clinical outcomes. International collaboration exists in many well founded co-operative groups for phase III trials, but progress may be more effective if there were also more investment of molecular and translational research into disease focused phase I/II clinical trials. Examples of new models for early translational and early phase trial collaboration include the European based EuroBoNeT network, the Sarcoma Alliance for Research through Collaboration network (SARC) and the new European collaborative translational trial network, EuroSarc.
Effect of TiO2 nanoparticles in the earthworm reproduction test
Authors: Schlich Karsten , Terytze Konstantin , Hund-Rinke Kerstin
Published: January 2012

Background

The increasing use of nanotechnology means that nanomaterials will enter the environment. Ecotoxicological data are therefore required so that adequate risk assessments can be carried out. In this study, we used a standardized earthworm reproduction test with Eisenia andrei to evaluate three types of TiO2 nanoparticles (NM-101, NM-102, NM-103). The test was performed in natural sandy soil (RefeSol 01A) following Organisation for Economic Co-operation and Development Test Guideline No. 222. The nanoparticles differed in several aspects, such as crystalline structure, size, and the presence or absence of a coating.

Results

Uncoated nanoparticles stimulated earthworm reproduction in a concentration-dependent manner during winter testing, increasing the number of offspring by up to 50% compared to the control. However, there was no stimulation when the same test was performed in the summer. This reflected an underlying circannual rhythm observed in the control soil, characterized by the production of a significantly larger number of juveniles in summer compared with that in winter. The effect of the uncoated TiO2 nanoparticles was to reduce or eliminate the circannual differences by increasing the reproductive rate in winter. Coated TiO2 nanoparticles did not influence earthworm reproduction.

Conclusion

TiO2 appears to affect earthworm reproductive activity by abolishing the circannual rhythm that depresses reproduction in the winter. Further experiments will be necessary to determine (1) the mode of action of the nanoparticles, (2) the important parameters causing the effect (e.g., relevant soil parameters), and (3) the environmental relevance of continuous earthworm reproduction we observed under laboratory conditions.
Heterologous expression and optimization using experimental designs allowed highly efficient production of the PHY US417 phytase in Bacillus subtilis 168
Authors: Farhat-Khemakhem Ameny , Ben Farhat Mounira , Boukhris Ines , Bejar Wacim , Bouchaala Kameleddine , Kammoun Radhouane , Maguin Emmanuelle , Bejar Samir , Chouayekh Hichem
Published: January 2012

To attempt cost-effective production of US417 phytase inBacillus subtilis, we developed an efficient system for its large-scale production in the generally recognized as safe microorganismB. subtilis168. Hence, thephyUS417 corresponding gene was cloned in the pMSP3535 vector, and for the first time for a plasmid carrying the pAMβ1 replication origin, multimeric forms of the resulting plasmid were used to transform naturally competentB. subtilis168 cells. Subsequently, a sequential optimization strategy based on Plackett-Burman and Box-Behnken experimental designs was applied to enhance phytase production by the recombinantBacillus. The maximum phytase activity of 47 U ml-1was reached in the presence of 12.5 g l-1of yeast extract and 15 g l-1of ammonium sulphate with shaking at 300 rpm. This is 73 fold higher than the activity produced by the native US417 strain before optimization. Characterization of the produced recombinant phytase has revealed that the enzyme exhibited improved thermostability compared to the wild type PHY US417 phytase strengthening its potential for application as feed supplement. Together, our findings strongly suggest that the strategy herein developed combining heterologous expression using a cloning vector carrying the pAMβ1 replication origin and experimental designs optimization can be generalized for recombinant proteins production inBacillus.
Elliptical dip moveout for 3D seismic imaging in the presence of azimuthal anisotropy
Authors: Shragge Jeffrey , Lumley David
Published: January 2012

Seismic images of the earth’s interior can be significantly distorted by complex wave propagation effects arising from 3D structural velocity variations, combined with the presence of azimuthal velocity anisotropy within some of the rock layers. Most image-processing techniques attempt to separate and compensate for both of these phenomena sequentially; they rarely address both simultaneously. These approaches implicitly assume that the effects of 3D structural velocity and azimuthal anisotropy are separable, whereas in fact, both effects are coupled together in the seismic data. In the presence of strong azimuthal velocity anisotropy, this can lead to significant errors in seismic velocity estimation and degraded quality of subsurface images, especially for large source-receiver offsets, wide azimuths, and steep geologic dips. Such imaging errors can greatly increase the uncertainty associated with exploring, characterizing, developing and monitoring subsurface geologic features for hydrocarbons, geothermal energy, [Formula: see text] sequestration, and other important geophysical imaging applications. Our approach simultaneously addressed velocity structure and azimuthal anisotropy by development of an elliptic dip moveout (DMO) operator. We combined the structural-velocity insensitivity of isotropic DMO with elliptic moveout representative of azimuthal velocity anisotropy. Forward and adjoint elliptical DMO operators were then cascaded together to form a single elliptical moveout (EMO) operation, which had a skewed saddle-like impulse response that resembles an isotropic azimuthal moveout operator. The EMO operator can be used as a prestack data conditioner, to estimate azimuthal anisotropy in a domain that is relatively insensitive to 3D velocity structure, or to compensate and map the data back to its original prestack domain in its approximately equivalent isotropic wavefield form. We demonstrated that EMO can reduce structural dip image errors of 10°–20° or more for realistic azimuthal velocity anisotropy values at far offsets.
Development of Nondestructive and Quantitative Elemental Analysis Method Using Calibration Curve between Muonic X-ray Intensity and Elemental Composition in Bronze
Authors: Ninomiya Kazuhiko , Nagatomo Takashi , Kubo Kenya , Ito Takashi U , Higemoto Wataru , Kita Makoto , Shinohara Atsushi , Strasser Patrick , Kawamura Naritoshi , Shimomura Koichiro , Miyake Yasuhiro , Saito Tsutomu
Published: January 2012

Quantitative elemental analysis method of a bulk material by examining the relation between intensity of muonic X-rays and elemental composition was developed. Using this new calibration method, we demonstrated quantitatively determination of the elemental composition inside of an ancient Chinese coin without sample destruction.
Exploration of Boundary between Charge-Density-Wave and Mott–Hubbard States in Quasi-One-Dimensional Halogen-Bridged Metal Complexes
Authors: Takaishi Shinya
Published: January 2012

In spite of a long history of quasi-one-dimensional halogen-bridged complexes (MX-chains), all Pt and Pd complexes form charge-density-wave (CDW) state (–X···M2+···X–M4+–X···), while all Ni complexes form Mott–Hubbard (MH) state (–X–Ni3+–X–Ni3+–X–), without exception. Although an interesting charge dynamics are expected at the boundary between the two states, no compound thus far reported forms both states. Thus, we have sought a phase boundary in bromo-bridged Pd compounds by decreasing Pd···Pd distance. In this article, we introduce the following two methods to decrease Pd···Pd distances: introduction of long alkyl chains which can afford attractive force between them, and partial substitution with smaller Ni ions, [Ni1−xPdx(chxn)2Br]Br2. In both systems, we have succeeded in realizing Pd3+ MH state. It has been revealed that the electronic state of bromo-bridged Pd compounds is determined by the Pd···Pd distances, in other words, CDW and MH states are stabilized when Pd···Pd distances are longer and shorter than 5.26 Å, respectively.
Dynamical Electron Mechanism of Double Proton Transfer in Formic Acid Dimer
Authors: Okuyama Michihiro , Takatsuka Kazuo
Published: January 2012

We study the dynamical electron mechanism of “double proton transfer” in formic acid dimer, which is a prototype of many double proton transfers in chemical and biological systems. Since the present double proton transfer takes place in a cyclic molecular system (a ring structure of dimerizing formic acids), and since the molecular structures before and after the double proton transfer are isomorphic to each other, the pathway of electron flow associated with the reaction cannot be determined in principle within the adiabatic electronic structures based on the Born–Oppenheimer approximation. It is also hard to determine whether “protons” are shifted in formic acid dimer or “hydrogen atoms” are migrated. The general distinction between them is often controversial in experimental studies, too. We identify the mechanism of such dynamics by highlighting the electron current and its pathway. To extract such information of dynamical electrons, we apply the semiclassical Ehrenfest theory, which takes an explicit account of all nuclei nonadiabatic electron wave packet dynamics. It turns out that the reaction proceeds in a concerted manner so that the chance of radical separation is very low and as though the net electronic flow is kept as low as possible to minimize the charge separation within a molecular complex.
Transition-metal-free Coupling Reactions of Aryl Halides
Authors: Shirakawa Eiji , Hayashi Tamio
Published: January 2012

Transition metal catalysis plays a leading role in C(sp2)–C(sp2) bond formation through substitution reactions. On the other hand, a similar type of substitution reaction has recently been achieved without the aid of transition-metal catalysts. In this review, recent transition-metal-free coupling reactions of aryl halides with arenes, alkenes, or aryl Grignard reagents are summarized in view of SRN1 reaction.
Single-component Layered Molecular Conductor, [Au(ptdt)2]
Authors: Zhou Biao , Yajima Hiroyuki , Idobata Yuki , Kobayashi Akiko , Kobayashi Tetsuya , Nishibori Eiji , Sawa Hiroshi , Kobayashi Hayao
Published: January 2012

A single-component layered molecular conductor, [Au(ptdt)2] (ptdt: propylenedithiotetrathiafulvalenedithiolate) was prepared. Unlike the single-component molecular metal, [Au(tmdt)2] (tmdt: trimethylenetetrathiafulvalenedithiolate) exhibiting three-dimensional compact molecular packing and antiferromagnetic transition at 110 K, the compressed pellet of the microcrystals of [Au(ptdt)2] exhibited fairly high conductivity and small temperature-independent paramagnetic susceptibility.
An unusual presentation of pulmonary cryptococcosis with co-existing disseminated tuberculosis in an AIDS patient
Authors: Chandrashekar U K , Acharya Vasudeva , Varghese George K , Rao Lakshmi
Published: January 2012

Although cryptococcosis with lung involvement is not rare in patients with HIV, it is rarely considered in the differential diagnosis of an abnormal chest roentgenogram. Pulmonary cryptococcosis with concomitant opportunistic infections is frequently seen among AIDS and its association with tuberculosis (TB) has been previously reported. Untreated pulmonary cryptococcosis in immunocompromised hosts usually becomes disseminated and results in considerable mortality despite antifungal therapy. We report a case of cryptococcosis with pulmonary involvement in a patient with coexisting disseminated TB in HIV infection.
Plant community dynamics in shortgrass steppe with grazing relaxation and imposition by large and small herbivores
Authors: Milchunas D.G.
Published: January 2012

Semiarid rangelands often respond slowly to rest/relaxation of grazing pressure by large herbivores, and the effects of grazing are most often inferred from this direction of study because the imposition of grazing onto previous ungrazed/lightly grazed areas occurred prior to the age of scientific studies. These rangelands host a diversity of small and large herbivores, but grazing studies most often concern effects of the large generalists. Here, the effects of herbivore body size on plant species richness and dominant species, and imposition and relaxation of grazing by large herbivores were studied by opening half of exclosures established in 1939 and building new exclosures to large herbivores, and to small-plus-large herbivores. Plant richness using sensitive species-area sampling was studied in a dry and a wet year, about 62 years after initiating the long-term experiment and about 6-10 years after initiating the altered designs. Convergence of the newly opened to large herbivore grazing treatment to the long-term grazed treatment occurred within 10 years, but convergence of the newly excluded to large herbivore treatment to the long-term excluded treatment had only partly occurred. This indicated that recovery from grazing is slow relative to imposition of grazing by large herbivores, but effects of the additional exclusion of small-plus-large herbivores occurred relatively rapidly. These results were mirrored by trajectories of convergence of the dominant species, and this is discussed with respect to implications for state-and-transition models. Short-term exclusion of small-plus-large herbivores resulted in greater richness than even long-term exclusion of only large herbivores, even though quantities consumed by small herbivores are much less than by large. Grazing effects on plant richness were large in the wet year, but the very dry year suppressed richness on all treatments. When sampling effort and area are the same, the numbers and attributes of species unique to a treatment are indicators of rareness of the richness and traits selected for by the treatment. More unique species were sampled in the small-plus-large herbivore exclosures when comparing body size, and the long-term large herbivore exclosures when comparing time of exclosure. Unique species encountered during sampling the ungrazed treatments were generally forbs, exotic and/or weedy invasive species, and often tall, annual species.