bluuebunny/crossref_metadata_2025 huggingface dataset:
The Responsibility to Protect in the Asia-Pacific Region
Authors: Bellamy Alex J. , Davies Sara E.
Published: December 2009

In 2005, governments around the world unanimously agreed to the principle of the responsibility to protect (R2P), which holds that all states have a responsibility to protect their populations from genocide and mass atrocities, that the international community should assist them to fulfil this duty, and that the international community should take timely and decisive measures to protect populations from such crimes when their host state fails to do so. Progressing R2P from words to deeds requires international consensus about the principle’s meaning and scope. To achieve a global consensus on this, we need to better understand the position of governments around the world, including in the Asia-Pacific region, which has long been associated with an enduring commitment to a traditional concept of sovereignty. The present article contributes to such an endeavour through its three sections. The first part charts the nature of the international consensus on R2P and examines the UN secretary-general’s approach. The second looks in detail at the positions of the Asia-Pacific region’s governments on the R2P principle. The final part explores the way forward for progressing the R2P principle in the Asia-Pacific region.
Enhancement of Energy Harvested from a Random Vibration Source by Magnetic Coupling of a Piezoelectric Cantilever
Authors: Lin Ji-Tzuoh , Alphenaar Bruce
Published: December 2009

It is demonstrated experimentally that the energy harvested from a random noise source by a piezoelectric cantilever can be substantially enhanced by introducing a magnetic coupling force. The coupled cantilever responds to a 1/f vibration spectrum (‘pink noise’) with chaotic motion that on average has larger amplitude than the non-chaotic motion of an uncoupled cantilever. A 50% increase in output voltage was observed in the coupled cantilever compared to the uncoupled cantilever. Calculations show that the magnetic force transforms the quadratic spring potential of the cantilever into a double valley of two potential wells. Fluctuations between the two potential minima increase the amplitude of the cantilever motion over a range of vibration frequencies.
Outsider in: Race, Attraction, and Research in New Orleans
Authors: Hawkins Robert L.
Published: December 2009

This article discusses how race, attraction, and a researcher’s identity with a community can both hamper and help qualitative research. Using a critical perspective, the author reflects on the experiences that shaped his research in New Orleans following Hurricane Katrina. He raises a series of ethical questions about the nexus of race, attraction, and identity in conducting qualitative interviews as a Black man with a largely low-income, female, and African American population. He explores the role that his self-identity played in study design, recruitment, and participation and addresses how he experienced race and dealt with attraction in his attempts to be regarded as an external insider by the community. Research considerations and ethical implications are explored.
Immunoglobulin-like transcript 3, an inhibitor of T cell activation, is reduced on blood monocytes during multiple sclerosis relapses and is induced by interferon β-1b
Authors: Jensen Mark A , Yanowitch Rachel N , Reder Anthony T , White David M , Arnason Barry GW
Published: December 2009

Immunoglobulin-like transcripts (ILTs) are immunoregulatory proteins that either activate or inhibit immune responses. ILT3 is inhibitory and is expressed preferentially by antigen-presenting cells. When its extracellular domain binds to an unidentified ligand of activated T cells, the T cell is silenced. Our objective was to study the expression of ILT3 on circulating monocytes in RRMS. Freshly isolated peripheral blood mononuclear cells were analyzed by multicolored flow cytometry. The proportion of ILT3+CD14+ monocytes in blood, and ILT3 levels expressed by them, is lower in untreated multiple sclerosis in relapse than in: (1) untreated multiple sclerosis in remission (p < 0.009); (2) stable interferon β-treated relapsing—remitting multiple sclerosis (p < 0.001) and; (3) healthy controls (p < 0.009). Glatiramer acetate-stimulated CD4 + T cells, co-cultured with freshly isolated monocytes, proliferate significantly better (p = 0.0017 for multiple sclerosis; p = 0.0015 for controls) when T cell interaction with monocyte-expressed ILT3 is blocked by anti-ILT3 antibody. Interferon β is beneficial in multiple sclerosis; why so remains unclear. Interferon β-1b markedly increases ILT3 expression in vitro by monocytes from multiple sclerosis patients and controls. These findings identify a putative novel mechanism for the therapeutic benefit bestowed by Interferon β and a new target for therapeutic intervention in relapsing—remitting multiple sclerosis.
Data extraction from a semi-structured electronic medical record system for outpatients: A model to facilitate the access and use of data for quality control and research
Authors: Kristianson Krister J. , Ljunggren Henrik , Gustafsson Lars L.
Published: December 2009

The use of clinical data from electronic medical records (EMRs) for clinical research and for evaluation of quality of care requires an extraction process. Many efforts have failed because the extracted data seemed to be unstructured, incomplete and ridden by errors. We have developed and tested a concept of extracting semi-structured EMRs (Journal III®, Profdoc®) data from 776 diabetes patients in a general practice clinic over a 5 year period. We used standard database management techniques commonly applied in clinical research in the pharmaceutical industry to clean up the data and make the data available for statistical analysis. The key problem was difficulties locating the data, as no standard way to enter the data in the EMR system was reinforced. Furthermore, no built-in edit checks to facilitate data entry were available. Laboratory, drug information and diagnostic data could be used directly while other data such as vital signs required much work to locate and become useful.
New Learnings from Old Understandings
Authors: Pere Lynne , Barnes Alex
Published: December 2009

This article demonstrates the absolute place of tikanga in research with Māori; tikanga being those ways of doing what is right for a given context centred in Māori values, beliefs, traditions and customs. A qualitative study involving Māori participants exposed large gaps in understanding of this importance beyond rhetoric. Western research processes surrounding consultation, consent and ownership of data were challenged by Māori philosophies and principles governed by tapu and noa. Adherence to understandings of ‘kanohi ki te kanohi’, ‘he kanohi kitea’, manaakitanga, ‘tangata mauri’, pōwhiri, mihimihi and karakia ensured informed and consensual participation. The rights and responsibilities of Iwi to conduct research in keeping with local kawa also ensured this participation was safe and respectful. This acknowledgement of ‘tino rangatiratanga’ was poorly understood, highlighting the significance of undertaking research with Māori in a way that takes for granted the validity and legitimacy of Māori in a context where Māori worldviews are centred.
Understanding Youth Resilience in Papua New Guinea through Life Story
Authors: Mafile'o Tracie , Kaise Api Unia
Published: December 2009

This life story qualitative research with Papua New Guinea youth shows how resilience is negotiated in a communal cultural context with limited access to formal social services. Using extracts from one life story, themes of family, faith and future are discussed. Implications for human services are the need to: engage informal social support systems through community development; recognize that young people have potential to change dramatically; and use a strengths-based approach. Implications for life story research are: methods can be culturally bound; stories are complex; stories can be collectively owned; and broad cultural representation is limited.
A Simulation Validation Method Based on Bootstrapping Applied to an Agent-based Simulation of the Bay of Biscay Historical Scenario
Authors: Champagne Lance E. , Hill Raymond R.
Published: December 2009

Combat, unlike many real-world processes, tends to be singular in nature. This makes statistical analysis of the combat data problematic. Building stochastic simulation models of combat scenarios provides a means of studying in some detail the particulars of a combat scenario provided that the model accurately captures the scenario. The scenario of interest in this paper is the WWII Bay of Biscay U-boat campaign, and the model is an agent-based simulation. The challenge is how to validate, or ensure the adequacy of, the simulation representation of the combat scenario with the actual scenario on the basis of comparing simulation output to typically small-sample-size actual combat data. In this paper we give the details of a new statistical methodology for use in validating a mission-level, agent-based model of a historical combat scenario. We use the Bay of Biscay agent-based simulation and develop a bootstrapping technique applied to the small-sample-size actual data from the Bay of Biscay campaign. Results from this bootstrapping statistical technique are compared with commonly used statistical techniques and are shown to improve the comparison of agent-based simulation output to actual real-world data.
Use of human amniotic membrane wrap in reducing perineural adhesions in a rabbit model of ulnar nerve neurorrhaphy
Authors: Kim S. S. , Sohn S. K. , Lee K. Y. , Lee M. J. , Roh M. S. , Kim C. H.
Published: December 2009

The object of this experimental study was to assess the effect of wrapping human amniotic membrane around a repaired ulnar nerve in a rabbit model of perineural adhesion. Ulnar nerves from 10 white New Zealand rabbits were exposed bilaterally, dissected and repaired. Human amniotic membrane was then wrapped around the repair site in one limb with no such wrap in the neurorrhaphy of the contralateral limb. Three months later, the same nerves were re-explored and removed using microsurgical external neurolysis. Perineural adhesion around the ulnar nerve was evaluated by blinded surgical dissection and scored using a visual 4-point qualitative scale. Extent and grade of fibrosis around repair sites were measured microscopically (×200) after Masson trichrome staining using measure of the depth of fibrosis and the grading criteria of adhesion. Quantitative morphometric analysis was also performed under light microscopy (×200) with the aid of a digital counter and virtual slide imaging software (ScanScope T2, Vista, CA, USA). Human amniotic membrane wrapped nerves showed significantly less perineural adhesion and fibrosis than controls ( P < 0.05). No nerve healing problems were encountered. This study suggests that human amniotic membrane application can reduce fibrosis and adhesion around neurorrhaphy sites in this animal model.
Structural and chemical evolution of super duplex stainless steel on activated tungsten inert gas welding process
Authors: Berthier A. , Paillard P. , Christien F.
Published: December 2009

In the present work, the welding parameters of tungsten inert gas (TIG) and activated tungsten inert gas (ATIG) welding processes were compared on duplex stainless steel with two protective gases (Ar and ArHeN2). The addition of an activating flux can improve the TIG welding process. The ATIG process involves an increase in the penetration as well as a reduction in the number of passes for a thickness higher than 2 mm for stainless steel or other metallic materials. Metallographic observations, chemical analyses and mechanical tests were performed. The results show the importance of the welding parameters, the protective gas and the use of a flux on the characteristics of the weld beads, its microstructure, its hardness and its behaviour in corrosion after welding.
Determinants of platelet number and regulation of thrombopoiesis
Authors: Kaushansky Kenneth
Published: December 2009

Our understanding of thrombopoiesis has improved greatly in the last two decades with the availability of in vitro assays of megakaryocyte progenitor cell growth, with the cloning and characterization of stem cell factor (SCF) and thrombopoietin (Tpo), the latter the primary humoral regulator of this process, and with the generation of genetically altered murine models of thrombopoietic failure and excess. While SCF affects developmentally early aspects of megakaryocyte growth, Tpo affects nearly all aspects of platelet production, from hematopoietic stem cell (HSC) self-renewal and expansion, through stimulation of megakaryocyte progenitor cell proliferation, to supporting their maturation into platelet-producing cells. The molecular and cellular mechanisms through which the marrow microenvironment and humoral mediators affect platelet production provide new insights into the interplay between intrinsic and extrinsic influences on hematopoiesis, and highlight new opportunities to translate basic biology into clinical advances.
Transfusion in the age of molecular diagnostics
Authors: Reid Marion E.
Published: December 2009

DNA-based tests are increasingly being used to predict a blood group phenotype to improve transfusion medicine. This is possible because genes encoding 29 of the 30 blood group systems have been cloned and sequenced, and the molecular bases associated with most antigens have been determined. RBCs carrying a particular antigen, if introduced into the circulation of an individual who lacks that antigen (through transfusion or pregnancy), can elicit an immune response. It is the antibody from such an immune response that causes problems in clinical practice and the reason why antigen-negative blood is required for safe transfusion. The classical method of testing for blood group antigens and antibodies is hemagglutination; however, it has certain limitations, some of which can be overcome by testing DNA. Such testing allows conservation of antibodies for confirmation by hemagglutination of predicted antigen-negativity. High-throughput platforms provide a means to test relatively large numbers of donors, thereby opening the door to change the way antigen-negative blood is provided to patients and to prevent immunization. This review summarizes how molecular approaches, in conjunction with conventional hemagglutination, can be applied in transfusion medicine.
ASH evidence-based guidelines: is the IgG-specific anti-PF4/heparin ELISA superior to the polyspecific ELISA in the laboratory diagnosis of HIT?
Authors: Cuker Adam , Ortel Thomas L.
Published: December 2009

You are asked to consult on a 76-year-old man admitted to the hospital with pneumonia and thrombocytopenia. Ten days before the current admission, he had undergone surgery to repair a small bowel obstruction. A preoperative platelet count had been normal. Following surgery, he received subcutaneous unfractionated heparin thromboprophylaxis until his discharge on post-operative day 5. In your differential diagnosis for the patient’s thrombocytopenia, you consider heparin-induced thrombocytopenia (HIT) and wish to order laboratory testing. In addition to a polyspecific anti-PF4/heparin ELISA for the diagnosis of HIT, your laboratory has recently begun to offer an IgG-specific ELISA. You wonder which of these assays performs better in the diagnosis of HIT.
Risk of future arterial cardiovascular events in patients with idiopathic venous thromboembolism
Authors: Green David
Published: December 2009

Venous and arterial thromboses have traditionally been considered distinct pathophysiologic entities. However, the two disorders have many features in common, and there is evidence that persons with venous thrombosis may be at greater risk for arterial events. The pathogenesis of both disorders includes endothelial injury, platelet activation, elevated levels of intrinsic clotting factors and inflammatory markers, increased fibrinogen, and impaired fibrinolysis. In addition, older age, obesity, dyslipidemia, and smoking predispose to both venous and arterial thrombosis. While the evidence that arterial disease is a risk factor for venous thrombosis is inconclusive, arterial disease does appear to occur with a modestly increased frequency in patients with a history of venous thromboembolism. Reported odds ratios in such patients were 1.2 for myocardial infarction, 1.3 for stroke, 2.3 for carotid plaque, and 4.3 for coronary calcification. Of note, in persons under age 40 with unprovoked venous thrombosis, the odds ratio for acute myocardial infarction was as high as 3.9. In general, however, venous disease is considered to be a weak risk factor for arterial thrombosis, and the use of agents specifically targeted to the prevention of heart attack or stroke in the majority of persons with VTE cannot be recommended at present.
ASH evidence-based guidelines: is there a role for second allogeneic transplant after relapse?
Authors: Thakar Monica S. , Forman Stephen J.
Published: December 2009

A 35-year-old male with a FLT3+ AML underwent allogeneic peripheral blood stem cell transplant using a myeloablative non-total body irradiation (TBI) conditioning regimen from his HLA-matched sibling donor. Following transplantation, he developed grade II acute graft-versus-host disease (GVHD) that resolved with increasing immunosuppression. The medications were subsequently discontinued, and he did not develop any evidence of chronic GVHD. Eighteen months after transplant, while off all immunosuppression, he developed fatigue and a blood count showed circulating blasts consistent with relapse of his disease. Among the various therapeutic questions is whether there is a role for a second allogeneic transplant to treat his disease and if so, at what time, with what conditioning, and with which type of donor.
The incidence, natural history, biology, and treatment of transformed lymphomas
Authors: Bernstein Steven H. , Burack W. Richard
Published: December 2009

Treatment of patients with transformed lymphoma presents a significant challenge to the practicing physician. Indeed, the transformation of follicular lymphoma to a more aggressive histology is inherent to the biology of this disease and is often associated with an aggressive clinical course, resulting in a poor prognosis. Recent population-based studies have better defined the incidence of this event, and recent laboratory studies have defined the molecular and immunological processes associated with transformation. These studies will be discussed in this review, as will the treatment options for these patients.
ASH evidence-based guidelines: what is the role of maintenance therapy in the treatment of multiple myeloma?
Authors: Ghobrial Irene M. , Stewart A. Keith
Published: December 2009

A 51-year-old male was diagnosed with an IgA multiple myeloma (MM) after having back pain for several months. His bone marrow showed 30% involvement with plasma cells and his cytogenetics showed t(4:14). His β2-microglobulin was 6.5 mg/dL at diagnosis and he had multiple lytic lesions, along with a creatinine of 2.3 mg/dL and significant anemia. Induction therapy with lenalidomide, bortezomib and dexamethasone was used, and he was able to achieve complete remission after 4 cycles of therapy. He then went on to receive high-dose chemotherapy with a single autologous stem cell transplant. He tolerated it well and now comes to discuss follow-up treatment plans. He wants to discuss maintenance therapy.
Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice
Authors: Caudell David , Harper David P. , Novak Rachel L. , Pierce Rachel M. , Slape Christopher , Wolff Linda , Aplan Peter D.
Published: December 2009

The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10.
Interconnecting molecular pathways in the pathogenesis and drug sensitivity of T-cell acute lymphoblastic leukemia
Authors: Sanda Takaomi , Li Xiaoyu , Gutierrez Alejandro , Ahn Yebin , Neuberg Donna S. , O'Neil Jennifer , Strack Peter R. , Winter Christopher G. , Winter Stuart S. , Larson Richard S. , von Boehmer Harald , Look A. Thomas
Published: December 2009

To identify dysregulated pathways in distinct phases of NOTCH1-mediated T-cell leukemogenesis, as well as small-molecule inhibitors that could synergize with or substitute for γ-secretase inhibitors (GSIs) in T-cell acute lymphoblastic leukemia (T-ALL) therapy, we compared gene expression profiles in a Notch1-induced mouse model of T-ALL with those in human T-ALL. The overall patterns of NOTCH1-mediated gene expression in human and mouse T-ALLs were remarkably similar, as defined early in transformation in the mouse by the regulation of MYC and its target genes and activation of nuclear factor-κB and PI3K/AKT pathways. Later events in murine Notch1-mediated leukemogenesis included down-regulation of genes encoding tumor suppressors and negative cell cycle regulators. Gene set enrichment analysis and connectivity map algorithm predicted that small-molecule inhibitors, including heat-shock protein 90, histone deacetylase, PI3K/AKT, and proteasome inhibitors, could reverse the gene expression changes induced by NOTCH1. When tested in vitro, histone deacetylase, PI3K and proteasome inhibitors synergized with GSI in suppressing T-ALL cell growth in GSI-sensitive cells. Interestingly, alvespimycin, a potent inhibitor of the heat-shock protein 90 molecular chaperone, markedly inhibited the growth of both GSI-sensitive and -resistant T-ALL cells, suggesting that its loss disrupts signal transduction pathways crucial for the growth and survival of T-ALL cells.
The hydrogenosomes of Psalteriomonas lanterna
Authors: de Graaf Rob M , Duarte Isabel , van Alen Theo A , Kuiper Jan WP , Schotanus Klaas , Rosenberg Jörg , Huynen Martijn A , Hackstein Johannes HP
Published: December 2009

Background

Hydrogenosomes are organelles that produce molecular hydrogen and ATP. The broad phylogenetic distribution of their hosts suggests that the hydrogenosomes of these organisms evolved several times independently from the mitochondria of aerobic progenitors. Morphology and 18S rRNA phylogeny suggest that the microaerophilic amoeboflagellate Psalteriomonas lanterna, which possesses hydrogenosomes and elusive "modified mitochondria", belongs to the Heterolobosea, a taxon that consists predominantly of aerobic, mitochondriate organisms. This taxon is rather unrelated to taxa with hitherto studied hydrogenosomes.

Results

Electron microscopy of P. lanterna flagellates reveals a large globule in the centre of the cell that is build up from stacks of some 20 individual hydrogenosomes. The individual hydrogenosomes are surrounded by a double membrane that encloses a homogeneous, dark staining matrix lacking cristae. The "modified mitochondria" are found in the cytoplasm of the cell and are surrounded by 1-2 cisterns of rough endoplasmatic reticulum, just as the mitochondria of certain related aerobic Heterolobosea. The ultrastructure of the "modified mitochondria" and hydrogenosomes is very similar, and they have the same size distribution as the hydrogenosomes that form the central stack.

The phylogenetic analysis of selected EST sequences (Hsp60, Propionyl-CoA carboxylase) supports the phylogenetic position of P. lanterna close to aerobic Heterolobosea (Naegleria gruberi). Moreover, this analysis also confirms the identity of several mitochondrial or hydrogenosomal key-genes encoding proteins such as a Hsp60, a pyruvate:ferredoxin oxidoreductase, a putative ADP/ATP carrier, a mitochondrial complex I subunit (51 KDa), and a [FeFe] hydrogenase.

Conclusion

Comparison of the ultrastructure of the "modified mitochondria" and hydrogenosomes strongly suggests that both organelles are just two morphs of the same organelle. The EST studies suggest that the hydrogenosomes of P. lanterna are physiologically similar to the hydrogenosomes of Trichomonas vaginalis and Trimastix pyriformis. Phylogenetic analysis of the ESTs confirms the relationship of P. lanterna with its aerobic relative, the heterolobosean amoeboflagellate Naegleria gruberi, corroborating the evolution of hydrogenosomes from a common, mitochondriate ancestor.
Genome-based polymorphic microsatellite development and validation in the mosquito Aedes aegypti and application to population genetics in Haiti
Authors: Lovin Diane D , Washington Katie O , deBruyn Becky , Hemme Ryan R , Mori Akio , Epstein Sarah R , Harker Brent W , Streit Thomas G , Severson David W
Published: December 2009

Background

Microsatellite markers have proven useful in genetic studies in many organisms, yet microsatellite-based studies of the dengue and yellow fever vector mosquito Aedes aegypti have been limited by the number of assayable and polymorphic loci available, despite multiple independent efforts to identify them. Here we present strategies for efficient identification and development of useful microsatellites with broad coverage across the Aedes aegypti genome, development of multiplex-ready PCR groups of microsatellite loci, and validation of their utility for population analysis with field collections from Haiti.

Results

From 79 putative microsatellite loci representing 31 motifs identified in 42 whole genome sequence supercontig assemblies in the Aedes aegypti genome, 33 microsatellites providing genome-wide coverage amplified as single copy sequences in four lab strains, with a range of 2-6 alleles per locus. The tri-nucleotide motifs represented the majority (51%) of the polymorphic single copy loci, and none of these was located within a putative open reading frame. Seven groups of 4-5 microsatellite loci each were developed for multiplex-ready PCR. Four multiplex-ready groups were used to investigate population genetics of Aedes aegypti populations sampled in Haiti. Of the 23 loci represented in these groups, 20 were polymorphic with a range of 3-24 alleles per locus (mean = 8.75). Allelic polymorphic information content varied from 0.171 to 0.867 (mean = 0.545). Most loci met Hardy-Weinberg expectations across populations and pairwise FST comparisons identified significant genetic differentiation between some populations. No evidence for genetic isolation by distance was observed.

Conclusion

Despite limited success in previous reports, we demonstrate that the Aedes aegypti genome is well-populated with single copy, polymorphic microsatellite loci that can be uncovered using the strategy developed here for rapid and efficient screening of genome supercontig assemblies. These loci are suitable for genetic and population studies using multiplex-PCR.
A recent duplication revisited: phylogenetic analysis reveals an ancestral duplication highly-conserved throughout the Oryza genus and beyond
Authors: Jacquemin Julie , Laudié Michèle , Cooke Richard
Published: December 2009

Background

The role of gene duplication in the structural and functional evolution of genomes has been well documented. Analysis of complete rice (Oryza sativa) genome sequences suggested an ancient whole genome duplication, common to all the grasses, some 50-70 million years ago and a more conserved segmental duplication between the distal regions of the short arms of chromosomes 11 and 12, whose evolutionary history is controversial.

Results

We have carried out a comparative analysis of this duplication within the wild species of the genusOryza, using a phylogenetic approach to specify its origin and evolutionary dynamics. Paralogous pairs were isolated for nine genes selected throughout the region in allOryzagenome types, as well as in two outgroup species,Leersia perrieriandPotamophila parviflora. AllOryzaspecies display the same global evolutionary dynamics but some lineage-specific features appear towards the proximal end of the duplicated region. The same level of conservation is observed between the redundant copies of the tetraploid speciesOryza minuta. The presence of orthologous duplicated blocks in the genome of the more distantly-related species,Brachypodium distachyon, strongly suggests that this duplication between chromosomes 11 and 12 was formed as part of the whole genome duplication common to all Poaceae.

Conclusion

Our observations suggest that recurrent but heterogeneous concerted evolution throughout theOryzagenus and in related species has led specifically to the extremely high sequence conservation occurring in this region of more than 2 Mbp.
Evaluation of prescribing patterns in a German network of CAM physicians for the treatment of patients with hypertension: a prospective observational study
Authors: Jeschke Elke , Ostermann Thomas , Vollmar Horst C , Kröz Matthias , Bockelbrink Angelina , Witt Claudia M , Willich Stefan N , Matthes Harald
Published: December 2009

Background

The management of hypertension is a key challenge in modern health systems. This study aimed to investigate hypertension treatment strategies among physicians specialized in complementary and alternative medicine (CAM) in Germany by analysing prescribing patterns and comparing these to the current treatment guidelines issued by the German Hypertension Society.

Methods

In this prospective, multicentre observational study, which included 25 primary care physicians specialized in CAM treatment, prescriptions and diagnoses were analysed for each consecutive hypertensive patient using routine electronic data. Data analysis was performed using univariate statistical tests (Chi square test, Cochran-Armitage trend test). Multiple logistic regression was used to determine factors associated with antihypertensive medication.

Results

In the year 2005, 1320 patients with 3278 prescriptions were included (mean age = 64.2 years (SD = 14.5), 63.5% women). Most patients were treated with conventional antihypertensive monotherapies (n = 838, 63.5%). Beta-blockers were the most commonly prescribed monotherapy (30.7%), followed by ACE inhibitors (24.0%). Combination treatment usually consisted of two antihypertensive drugs administered either as separate agents or as a coformulation. The most common combination was a diuretic plus an ACE inhibitor (31.2% of dual therapies). Patient gender, age, and comorbidities significantly influenced which treatment was prescribed. 187 patients (14.2%) received one or more CAM remedies, most of which were administered in addition to classic monotherapies (n = 104). Men (OR = 0.66; 95% CI: 0.54-0.80) and patients with diabetes (OR = 0.55; 95% CI: 0.42-0.0.73), hypercholesterolaemia (OR = 0.59; 95% CI: 0.47-0.75), obesity (OR = 0.74; 95% CI: 0.57-0.97), stroke (OR = 0.54; 95% CI: 0.40-0.74), or prior myocardial infarction (OR = 0.37; 95% CI: 0.17-0.81) were less likely to receive CAM treatment.

Conclusions

The large majority of antihypertensive treatments prescribed by CAM physicians in the present study complied with the current German Hypertension Society treatment guidelines. Deviations from the guidelines were observed in one of every seven patients receiving some form of CAM treatment.
Cadmium burden and the risk and phenotype of prostate cancer
Authors: Chen Yi-Chun , Pu Yeong S , Wu Hsi-Chin , Wu Tony T , Lai Ming Kuen , Yang Chun Y , Sung Fung-Chang
Published: December 2009

Background

Studies on the association between prostate cancer and cadmium exposure have yielded conflicting results. This study explored cadmium burden on the risk and phenotype of prostate cancer in men with no evident environmental exposure.

Methods

Hospital-based 261 prostate cancer cases and 267 controls with benign diseases were recruited from four hospitals in Taiwan. Demographic, dietary and lifestyle data were collected by standardized questionnaires. Blood cadmium (BCd) and creatinine-adjusted urine cadmium (CAUCd) levels were measured for each participant. Statistical analyses measured the prostate cancer risk associated with BCd and CAUCd separately, controlling for age, smoking and institution. BCd and CAUCd levels within cases were compared in relation to the disease stage and the Gleason score.

Results

High family income, low beef intake, low dairy product consumption and positive family history were independently associated with the prostate carcinogenesis. There was no difference in BCd levels between cases and controls (median, 0.88 versus 0.87 μg/l, p = 0.45). Cases had lower CAUCd levels than controls (median, 0.94 versus 1.40 μg/g creatinine, p = 0.001). However, cases with higher BCd and CAUCd levels tended to be at more advanced stages and to have higher Gleason scores. The prostate cancer cases with Gleason scores of ≥ 8 had an odds ratio of 2.89 (95% confidence interval 1.25-6.70), compared with patients with scores of 2-6.

Conclusion

Higher CAUCd and BCd levels may be associated with advanced cancer phenotypes, but there was only a tenuous association between cadmium and prostate cancer.
Overexpression of inhibitor of DNA-binding (ID)-1 protein related to angiogenesis in tumor advancement of ovarian cancers
Authors: Maw Min Khine , Fujimoto Jiro , Tamaya Teruhiko
Published: December 2009

Background

The inhibitor of DNA-binding (ID) has been involved in cell cycle regulation, apoptosis and angiogenesis. This prompted us to study ID functions in tumor advancement of ovarian cancers.

Methods

Sixty patients underwent surgery for ovarian cancers. In ovarian cancers, the levels of ID-1, ID-2 and ID-3 mRNAs were determined by real-time reverse transcription-polymerase chain reaction. The histoscore with the localization of ID-1 was determined by immunohistochemistry. Patient prognosis was analyzed with a 36-month survival rate. Microvessel counts were determined by immunohistochemistry for CD34 and factor VIII-related antigen.

Results

ID-1 histoscores and mRNA levels both significantly (p < 0.001) increased in ovarian cancers according to clinical stage, regardless of histopathological type. Furthermore, 30 patients with high ID-1 expression had a lower survival rate (53%) compared to patients with low ID-1 expression (80%). ID-1 histoscores and mRNA levels significantly (p < 0.0001) correlated with microvessel counts in ovarian cancers.

Conclusion

ID-1 increased in ovarian cancer cells during tumor progression. Moreover, ID-1 expression levels correlated with microvessel counts. Therefore, ID-1 might work on tumor advancement via angiogenesis and is considered to be a candidate for a prognostic indicator in ovarian cancers.
IL4 gene polymorphism and previous malaria experiences manipulate anti-Plasmodium falciparum antibody isotype profiles in complicated and uncomplicated malaria
Authors: Tangteerawatana Piyatida , Perlmann Hedvig , Hayano Masashi , Kalambaheti Thareerat , Troye-Blomberg Marita , Khusmith Srisin
Published: December 2009

Background

TheIL4-590 gene polymorphism has been shown to be associated with elevated levels of anti-Plasmodium falciparumIgG antibodies and parasite intensity in the malaria protected Fulani of West Africa. This study aimed to investigate the possible impact ofIL4-590C/T polymorphism on anti-P. falciparumIgG subclasses and IgE antibodies levels and the alteration of malaria severity in complicated and uncomplicated malaria patients with or without previous malaria experiences.

Methods

Anti-P.falciparumIgG subclasses and IgE antibodies in plasma of complicated and uncomplicated malaria patients with or without previous malaria experiences were analysed using ELISA.IL4-590 polymorphisms were genotyped using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by Oneway ANOVA. Genotype differences were tested by Chi-squared test.

Results

TheIL4-590T allele was significantly associated with anti-P. falciparumIgG3 antibody levels in patients with complicated (P= 0.031), but not with uncomplicated malaria (P= 0.622). Complicated malaria patients with previous malaria experiences carryingIL4-590TT genotype had significantly lower levels of anti-P. falciparumIgG3 (P= 0.0156), while uncomplicated malaria patients with previous malaria experiences carrying the same genotype had significantly higher levels(P= 0.0206) compared to theirIL4-590 counterparts. The different anti-P. falciparumIgG1 and IgG3 levels among IL4 genotypes were observed. Complicated malaria patients with previous malaria experiences tended to have lower IgG3 levels in individuals carrying TT when compared to CT genotypes (P= 0.075). In contrast, complicated malaria patients without previous malaria experiences carrying CC genotype had significantly higher anti-P. falciparumIgG1 than those carrying either CT or TT genotypes (P= 0.004,P= 0.002, respectively).

Conclusion

The results suggest thatIL4-590C or T alleles participated differently in the regulation of anti-malarial antibody isotype profiles in primary and secondary malaria infection and, therefore, could play an important role in alteration of malaria severity.
A replication study of the association between the IL12B promoter allele CTCTAA and susceptibility to cerebral malaria in Thai population
Authors: Naka Izumi , Patarapotikul Jintana , Tokunaga Katsushi , Hananantachai Hathairad , Tsuchiya Naoyuki , Ohashi Jun
Published: December 2009

Background

Interleukin-12 (IL-12), a heterodimeric cytokine composed of p35 and p40 subunits, has been thought to play an important role in the pathogenesis of malaria. The IL-12p40 subunit is encoded by the IL12B gene. An IL12B promoter allele, CTCTAA, at rs17860508 has been reported to be associated with susceptibility to cerebral malaria in African populations. However, this association has not so far been replicated in non-African populations.

Methods

To examine whether the CTCTAA allele is associated with susceptibility to cerebral malaria in Asian populations, 303 Thai patients with Plasmodium falciparum malaria (109 cerebral malaria and 194 mild malaria patients) were genotyped for rs17860508 by PCR-direct sequencing.

Results

The CTCTAA allele showed a significant association with susceptibility to cerebral malaria in the Thai population (allelic OR = 1.37; one sided P-value = 0.030).

Conclusions

The existence of a significant association between the CTCTAA allele and susceptibility to cerebral malaria was confirmed in Southeast Asian population, which was previously reported in African populations.
Intein-mediated site-specific conjugation of Quantum Dots to proteins in vivo
Authors: Charalambous Anna , Andreou Maria , Skourides Paris A
Published: December 2009

We describe an intein based method to site-specifically conjugate Quantum Dots (QDs) to target proteins in vivo. This approach allows the covalent conjugation of any nanostructure and/or nanodevice to any protein and thus the targeting of such material to any intracellular compartment or signalling complex within the cells of the developing embryo. We genetically fused a pleckstrin-homology (PH) domain with the N-terminus half of a split intein (IN). The C-terminus half (IC) of the intein was conjugated to QDs in vitro. IC-QD's and RNA encoding PH-IN were microinjected into Xenopus embryos. In vivo intein-splicing resulted in fully functional QD-PH conjugates that could be monitored in real time within live embryos. Use of Near Infra Red (NIR)-emitting QDs allowed monitoring of QD-conjugates within the embryo at depths where EGFP is undetectable demonstrating the advantages of QD's for this type of experiment. In conclusion, we have developed a novel in vivo methodology for the site-specific conjugation of QD's and other artificial structures to target proteins in different intracellular compartments and signaling complexes.
Adolescent body satisfaction: the role of perceived parental encouragement for physical activity
Authors: Savage Jennifer S , DiNallo Jennifer M , Downs Danielle Symons
Published: December 2009

Background

Parents play an important role in the development of children's health behaviors, but less is known about the role of parental encouragement for physical activity (PA) on youth PA behavior and body image satisfaction. The purposes of this study were to: (1) longitudinally assess whether adolescent PA at age 15 mediates the effect of perceived parental encouragement for PA at age 15 for predicting adolescent body satisfaction at age 16, while controlling for body mass index (BMI), and (2) examine the extent to which adolescent sex moderates this association.

Methods

Participants were 379 boys and girls assessed at 15 and 16 years of age, who completed surveys as part of a larger longitudinal study in their health/physical education classes in a school district in Central Pennsylvania. Participants completed measures of their perception of parental encouragement for PA, PA behavior, body satisfaction, and height and weight to calculate BMI at age 15 and 16 (i.e., 10th and 11th grades). Pearson correlations were used to examine the association among the study variables and hierarchical regression analyses were used to predict body satisfaction at age 16.

Results

Perceived encouragement for PA from fathers, but not mothers, at age 15, was significantly associated with adolescent PA at age 15 and body satisfaction scores at age 16. Adolescents reporting higher PA behavior and perceived encouragement for PA from fathers at age 15 had higher body satisfaction scores at age 16. Moreover, adolescent PA at age 15 mediated the association between perceived fathers' encouragement for PA at age 15 and adolescent body satisfaction at age 16, when controlling for BMI. Examining the moderating effect of adolescent sex on this association revealed that adolescent PA no longer mediated the association between perceived encouragement for PA from fathers and adolescent body satisfaction, and sex moderated this association.

Discussion

These findings suggest that, regardless of adolescent BMI, fathers may play an instrumental role in adolescents' body image satisfaction by positively influencing PA behavior. However, the influence of perceived encouragement for PA from fathers on adolescent body satisfaction and PA behavior may differ for boys and girls.
Increased immunogenicity of surviving tumor cells enables cooperation between liposomal doxorubicin and IL-18
Authors: Alagkiozidis Ioannis , Facciabene Andrea , Carpenito Carmine , Benencia Fabian , Jonak Zdenka , Adams Sarah , Carroll Richard G , Gimotty Phyllis A , Hammond Rachel , Danet-Desnoyers Gwen-äel , June Carl H , Powell Daniel J , Coukos George
Published: December 2009

Background

Liposomal doxorubicin (Doxil) is a cytotoxic chemotherapy drug with a favorable hematologic toxicity profile. Its active drug, doxorubicin, has interesting immunomodulatory properties. Here, the effects of Doxil on surviving tumor cell immunophenotype were investigated.

Methods

Using ID8 murine ovarian cancer cells, the immunomodulatory effects of Doxil were studied by measuring its impact on ovarian cancer cell expression of MHC class-I and Fas, and susceptibility to immune attack in vitro. To evaluate the ability of Doxil to cooperate with cancer immunotherapy, the interaction between Doxil and Interleukin 18 (IL-18), a pleiotropic immunostimulatory cytokine, was investigated in vivo in mice bearing ID8-Vegf tumors.

Results

While Doxil killed ID8 tumor cells in a dose-dependent manner, tumor cells escaping Doxil-induced apoptosis upregulated surface expression of MHC-I and Fas, and were sensitized to CTL killing and Fas-mediated death in vitro. We therefore tested the hypothesis that the combination of immunotherapy with Doxil provides positive interactions. Combination IL-18 and Doxil significantly suppressed tumor growth compared with either monotherapy in vivo and uniquely resulted in complete tumor regression and long term antitumor protection in a significant proportion of mice.

Conclusion

These data demonstrate that Doxil favorably changes the immunophenotype of a large fraction of the tumor that escapes direct killing thus creating an opportunity to expand tumor killing by immunotherapy, which can be capitalized through addition of IL-18 in vivo.
Computer aided data acquisition tool for high-throughput phenotyping of plant populations
Authors: Vankadavath Raju Naik , Hussain Appibhai Jakir , Bodanapu Reddaiah , Kharshiing Eros , Basha Pinjari Osman , Gupta Soni , Sreelakshmi Yellamaraju , Sharma Rameshwar
Published: December 2009

Background

The data generated during a course of a biological experiment/study can be sometimes be massive and its management becomes quite critical for the success of the investigation undertaken. The accumulation and analysis of such large datasets often becomes tedious for biologists and lab technicians. Most of the current phenotype data acquisition management systems do not cater to the specialized needs of large-scale data analysis. The successful application of genomic tools/strategies to introduce desired traits in plants requires extensive and precise phenotyping of plant populations or gene bank material, thus necessitating an efficient data acquisition system.

Results

Here we describe newly developed software "PHENOME" for high-throughput phenotyping, which allows researchers to accumulate, categorize, and manage large volume of phenotypic data. In this study, a large number of individual tomato plants were phenotyped with the "PHENOME" application using a Personal Digital Assistant (PDA) with built-in barcode scanner in concert with customized database specific for handling large populations.

Conclusion

The phenotyping of large population of plants both in the laboratory and in the field is very efficiently managed using PDA. The data is transferred to a specialized database(s) where it can be further analyzed and catalogued. The "PHENOME" aids collection and analysis of data obtained in large-scale mutagenesis, assessing quantitative trait loci (QTLs), raising mapping population, sampling of several individuals in one or more ecological niches etc.