bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent complete molecular remission after nilotinib and graft-versus-leukemia effect in an acute lymphoblastic leukemia patient with cytogenetic relapse after allogeneic stem cell transplantation
Authors: Farnsworth Paul , Ward David , Reddy Vijay 
Published: December 2012

Abstract
We report the successful treatment and sustained molecular remission using single agent nilotinib in a relapsed Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia patient after allogeneic hematopoietic stem cell transplantation. Compared to previously published studies, this is the first report where a patient did not receive additional chemotherapy after relapse, nor did she receive donor lymphocyte infusions. With nilotinib, the patient reverted back to normal blood counts and 100% donor reconstitution by single tandem repeat (STR) chimerism analysis in the bone marrow and in peripheral blood, granulocytes, T and B-lymphocytes. This report also highlights the use of nilotinib in combination with extracorporeal photopheresis (ECP) for concomitant graft-versus-host disease. Our data suggests that ECP, together with nilotinib, did not adversely affect the overall Graft-versus-leukemia (GVL) effect.
Purification and properties of S-hydroxymethylglutathione dehydrogenase of Paecilomyces variotii no. 5, a formaldehyde-degrading fungus
Authors: Fukuda Ryohei , Nagahama Kazuhiro , Fukuda Kohsai , Ekino Keisuke , Oka Takuji , Nomura Yoshiyuki 
Published: December 2012

Abstract

S-hydroxymethylglutathione dehydrogenase from Paecilomyces variotii No. 5 strain (NBRC 109023), isolated as a formaldehyde-degrading fungus, was purified by a procedure that included ammonium sulfate precipitation, DEAE-Sepharose and hydroxyapatite chromatography and isoelectrofocusing. Approximately 122-fold purification was achieved with a yield of 10.5%. The enzyme preparation was homogeneous as judged by sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE). The molecular mass of the purified enzyme was estimated to be 49 kDa by SDS-PAGE and gel filtration, suggesting that it is a monomer. Enzyme activity was optimal at pH 8.0 and was stable in the range of pH 7.0–10. The optimum temperature for activity was 40°C and the enzyme was stable up to 40°C. The isoelectric point was pH 5.8. Substrate specificity was very high for formaldehyde. Besides formaldehyde, the only aldehyde or alcohol tested that served as a substrate was pyruvaldehyde. Enzyme activity was enhanced by several divalent cations such as Mn2+ (179%), Ba2+ (132%), and Ca2+ (112%) but was completely inhibited by Ni2+, Fe3+, Hg2+, p-chloromercuribenzoate (PCMB) and cuprizone. Inactivation of the enzyme by sulfhydryl reagents (Hg2+ and PCMB) indicated that the sulfhydryl group of the enzyme is essential for catalytic activity.
Optimization of lipid production by the oleaginous yeast Lipomyces starkeyi by random mutagenesis coupled to cerulenin screening
Authors: Tapia V Eulalia , Anschau Andréia , Coradini Alessandro LV , T Franco Telma , Deckmann Ana Carolina 
Published: December 2012

Abstract
In this work we performed assays for the genetic improvement of the oleaginous yeast Lipomyces starkeyi DSM 70296 focusing on its utilization for lipid biosynthesis from renewable sources. The genetic optimization was carried out by random mutagenesis by ultraviolet irradiation and mutant selection by cerulenin, a compound displaying inhibitory effects on lipid biosynthesis. Mutants demonstrating normal growth in presence of cerulenin were considered as good candidates for further studies. Using this strategy, we selected 6 mutants for further studies, in which their productivities were evaluated by fermentation in shaken flasks and bioreactor. The evaluation of the fermentative performance of mutants was carried out using xylose as sole carbon source; the fermentation of wild-type strain was used as reference. Using this strategy it was possible to identify one mutant (termed A1) presenting a significant increase in the productivity rates of both biomass and lipid in comparison to wild-type strain. A1 mutant was further studied in bioreactor using the same fermentation parameters optimized for L. starkeyi lipid production from a mixed carbon source (xylose:glucose), as previously determined by other studies in our laboratory. A1 presented a productivity increase of 15.1% in biomass and 30.7% in lipid productivity when compared to the wild-type strain with a similar fatty acid composition, despite a slight increase (approx. 7%) on the unsaturated fraction. Our work demonstrates the feasibility of the random mutagenesis strategy coupled with mutant selection based on cerulenin screening for the genetic improvement of the oleaginous yeast L. starkeyi.
FDG-PET is a good biomarker of both early response and acquired resistance in BRAFV600 mutant melanomas treated with vemurafenib and the MEK inhibitor GDC-0973
Authors: Baudy Andreas R , Dogan Taner , Flores-Mercado Judith E , Hoeflich Klaus P , Su Fei , van Bruggen Nicholas , Williams Simon-Peter 
Published: December 2012

Abstract

Background
The BRAF inhibitor, vemurafenib, has recently been approved for the treatment of metastatic melanoma in patients harboring BRAFV600 mutations. Currently, dual BRAF and MEK inhibition are ongoing in clinical trials with the goal of overcoming the acquired resistance that has unfortunately developed in some vemurafenib patients. FDG-PET measures of metabolic activity are increasingly employed as a pharmacodynamic biomarker for guiding single-agent or combination therapies by gauging initial drug response and monitoring disease progression. However, since tumors are inherently heterogeneous, investigating the effects of BRAF and MEK inhibition on FDG uptake in a panel of different melanomas could help interpret imaging outcomes.

Methods

18 F-FDG uptake was measured in vitro in cells with wild-type and mutant (V600) BRAF, and in melanoma cells with an acquired resistance to vemurafenib. We treated the cells with vemurafenib alone or in combination with MEK inhibitor GDC-0973. PET imaging was used in mice to measure FDG uptake in A375 melanoma xenografts and in A375 R1, a vemurafenib-resistant derivative. Histological and biochemical studies of glucose transporters, the MAPK and glycolytic pathways were also undertaken.

Results
We demonstrate that vemurafenib is equally effective at reducing FDG uptake in cell lines harboring either heterozygous or homozygous BRAFV600 but ineffective in cells with acquired resistance or having WT BRAF status. However, combination with GDC-0973 results in a highly significant increase of efficacy and inhibition of FDG uptake across all twenty lines. Drug-induced changes in FDG uptake were associated with altered levels of membrane GLUT-1, and cell lines harboring RAS mutations displayed enhanced FDG uptake upon exposure to vemurafenib. Interestingly, we found that vemurafenib treatment in mice bearing drug-resistant A375 xenografts also induced increased FDG tumor uptake, accompanied by increases in Hif-1α, Sp1 and Ksr protein levels. Vemurafenib and GDC-0973 combination efficacy was associated with decreased levels of hexokinase II, c-RAF, Ksr and p-MEK protein.

Conclusions
We have demonstrated that 18 F-FDG-PET imaging reflects vemurafenib and GDC-0973 action across a wide range of metastatic melanomas. A delayed post-treatment increase in tumor FDG uptake should be considered carefully as it may well be an indication of acquired drug resistance.

Trial registration
ClinicalTrials.gov NCT01271803
Influence of latentToxoplasmainfection on human personality, physiology and morphology: pros and cons of theToxoplasma–human model in studying the manipulation hypothesis
Authors: Flegr Jaroslav 
Published: December 2012

SummaryThe parasitic protozoan Toxoplasma gondii infects about one-third of the population of developed countries. The life-long presence of dormant stages of this parasite in the brain and muscular tissues of infected humans is usually considered asymptomatic from the clinical point of view. In the past 20 years, research performed mostly on military personnel, university students, pregnant women and blood donors has shown that this ‘asymptomatic’ disease has a large influence on various aspects of human life. Toxoplasma-infected subjects differ from uninfected controls in the personality profile estimated with two versions of Cattell’s 16PF, Cloninger’s TCI and Big Five questionnaires. Most of these differences increase with the length of time since the onset of infection, suggesting that Toxoplasma influences human personality rather than human personality influencing the probability of infection. Toxoplasmosis increases the reaction time of infected subjects, which can explain the increased probability of traffic accidents in infected subjects reported in three retrospective and one very large prospective case-control study. Latent toxoplasmosis is associated with immunosuppression, which might explain the increased probability of giving birth to a boy in Toxoplasma-infected women and also the extremely high prevalence of toxoplasmosis in mothers of children with Down syndrome. Toxoplasma-infected male students are about 3 cm taller than Toxoplasma-free subjects and their faces are rated by women as more masculine and dominant. These differences may be caused by an increased concentration of testosterone. Toxoplasma also appears to be involved in the initiation of more severe forms of schizophrenia. At least 40 studies confirmed an increased prevalence of toxoplasmosis among schizophrenic patients. Toxoplasma-infected schizophrenic patients differ from Toxoplasma-free schizophrenic patients by brain anatomy and by a higher intensity of the positive symptoms of the disease. Finally, five independent studies performed in blood donors, pregnant women and military personnel showed that RhD blood group positivity, especially in RhD heterozygotes, protects infected subjects against various effects of latent toxoplasmosis, such as the prolongation of reaction times, an increased risk of traffic accidents and excessive pregnancy weight gain. The modern human is not a natural host of Toxoplasma. Therefore, it can only be speculated which of the observed effects of latent toxoplasmosis are the result of the manipulation activity of the Toxoplasma aimed to increase the probability of its transmission from a natural intermediate to the definitive host by predation, and which are just side effects of chronic infection.
Multidimensionality in parasite-induced phenotypic alterations: ultimateversusproximate aspects
Authors: Cézilly Frank , Favrat Adrien , Perrot-Minnot Marie-Jeanne 
Published: December 2012

SummaryIn most cases, parasites alter more than one dimension in their host phenotype. Although multidimensionality in parasite-induced phenotypic alterations (PIPAs) seems to be the rule, it has started to be addressed only recently. Here, we critically review some of the problems associated with the definition, quantification and interpretation of multidimensionality in PIPAs. In particular, we confront ultimate and proximate accounts, and evaluate their own limitations. We end up by introducing several suggestions for the development of future research, including some practical guidelines for the quantitative analysis of multidimensionality in PIPAs.
Toxoplasma gondii infection and behaviour – location, location, location?
Authors: McConkey Glenn A. , Martin Heather L. , Bristow Greg C. , Webster Joanne P. 
Published: December 2012

Summary
Parasite location has been proposed as an important factor in the behavioural changes observed in rodents infected with the protozoan Toxoplasma gondii. During the chronic stages of infection, encysted parasites are found in the brain but it remains unclear whether the parasite has tropism for specific brain regions. Parasite tissue cysts are found in all brain areas with some, but not all, prior studies reporting higher numbers located in the amygdala and frontal cortex. A stochastic process of parasite location does not, however, seem to explain the distinct and often subtle changes observed in rodent behaviour. One factor that could contribute to the specific changes is increased dopamine production by T. gondii. Recently, it was found that cells encysted with parasites in the brains of experimentally infected rodents have high levels of dopamine and that the parasite encodes a tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of this neurotransmitter. A mechanism is proposed that could explain the behaviour changes due to parasite regulation of dopamine. This could have important implications for T. gondii infections in humans.
Treatment of Methicillin-Resistant Staphylococcus aureus Infections with a Minimal Inhibitory Concentration of 2 μg/mL to Vancomycin: Old (Trimethoprim/Sulfamethoxazole) versus New (Daptomycin or Linezolid) Agents
Authors: Campbell Michelle L , Marchaim Dror , Pogue Jason M , Sunkara Bharath , Bheemreddy Suchitha , Bathina Pradeep , Pulluru Harish , Chugh Neelu , Wilson Melanie N , Moshos Judy , Ku Kimberley , Hayakawa Kayoko , Martin Emily T , Lephart Paul R , Rybak Michael J , Kaye Keith S 
Published: December 2012

Background: Guidelines recommend that agents other than vancomycin be considered for some types of infection due to methicillin-resistant Staphylococcus aureus (MRSA) when the minimum inhibitory concentration (MIC) to vancomycin is 2 μg/mL or more. Alternative therapeutic options include daptomycin and linezolid, 2 relatively new and expensive drugs, and trimethoprim/sulfamethoxazole (TMP/SMX), an old and inexpensive agent. Objective: To compare the clinical efficacy and potential cost savings associated with use of TMP/SMX compared to linezolid and daptomycin. Methods: A retrospective study was conducted at Detroit Medical Center. For calendar year 2009, unique adults (age >18 years) with infections due to MRSA with an MIC to vancomycin of 2 μg/mL were included if they received 2 or more doses of TMP/SMX and/or daptomycin and/or linezolid. Data were abstracted from patient charts and pharmacy records. Results: There were 328 patients included in the study cohort: 143 received TMP/SMX alone, 89 received daptomycin alone, 75 received linezolid alone, and 21 patients received a combination of 2 or more of these agents. In univariate analysis, patients who received TMP/SMX alone had significantly better outcomes, including in-hospital (p = 0.003) and 90-day mortality (p < 0.001) compared to patients treated with daptomycin or linezolid. Patients receiving TMP/SMX were also younger (p < 0.001), had fewer comorbid conditions (p < 0.001), had less severe acute severity of illness (p < 0.001), and received appropriate therapy more rapidly (p = 0.001). In multivariate models the association between TMP/SMX treatment and mortality was no longer significant. Antimicrobial cost savings associated with using TMP/SMX averaged $2067.40 per patient. Conclusions: TMP/SMX monotherapy compared favorably to linezolid and daptomycin in terms of treatment efficacy and mortality. Use of TMP/SMX instead of linezolid or daptomycin could potentially significantly reduce antibiotic costs. TMP/SMX should be considered for the treatment of MRSA infection with MIC of 2 μg/mL to vancomycin.
K-Ar Age Constraints on the Origin Of Micaceous Minerals in Savannah River Site Soils, South Carolina, USA
Authors: Naumann Thomas E. , Elliott W. Crawford , Wampler J. M. 
Published: December 2012

AbstractK-Ar measurements were used in this study of upland Savannah River Site soils to distinguish between sorbed K and the K remaining in remnants of primary minerals. Study of sorbed K contributes to understanding further the interaction of alkali metals (Cs in particular) with the soils. Primary mineral K and the associated radiogenic Ar were studied to characterize soil mica with respect to its provenance and its relationship to hydroxy-interlayered vermiculite. K-Ar age values of Na-saturated clay fractions from five samples of these soils range in age from 270 to 370 Ma. After a moderate acid treatment (6% HNO3 v/v, ~1 mol dm-3, 3 h, 80°C) of the clay fractions, K-Ar age values (270-325 Ma) were little changed on the whole, but they were more closely grouped near 300 Ma. Earlier work had shown that most of the K in these soils is found in material resistant to moderate acid extraction. The K-Ar age values show that this acid-resistant material is much older than any pedogenic minerals could be, even much older than the sedimentary parent rocks from which the soils were derived. These observations support earlier inferences by others that the K in these well leached soils is largely in remnants of primary muscovite from the parent sediments. Age values near 300 Ma suggest that the muscovite is largely from proximal Piedmont terranes of the Appalachian orogen, where the K-Ar relationship in most micas was set by Alleghanian tectonic processes late in the Paleozoic Era. The structural location of the K within mica, shown by the retention of the associated radiogenic Ar, is in contrast to the sorption-dominated behavior of the Cs and most of the Rb in these soils during pedogenesis. Stronger acid treatment (~6 mol dm-3 HNO3, 3 h, 100°C) extracted substantial fractions of both the K and the radiogenic Ar from bulk-soil portions, indicating destruction of some of the primary mica. K-Ar age values for the sand-rich bulk soils were not useful for this study because the sand contains excess radiogenic Ar, probably in sand-sized vein quartz.
Japan's Failed Experiment: The DPJ and Institutional Change for Political Leadership
Authors: Shinoda Tomohito 
Published: December 2012

Abstract
With the establishment of the DPJ government, Prime Minister Hatoyama Yukio introduced a series of institutional changes in order to transform the existing bureaucracy-controlled government and to establish political leadership. These changes, however, created instability and irregularity in Japanese politics. As a result, they were reversed by his successors.
The Monarchy and Party Politics in Malaysia in the Era of Abdullah Ahmad Badawi (2003–09): The Resurgence of the Role of Protector
Authors: Abdul Hamid Ahmad Fauzi , Ismail Muhamad Takiyuddin 
Published: December 2012

Abstract
This article argues that calls for the reassertion of royal power in Malaysia pre-dated the historic twelfth general elections of 2008. The erosion of UMNO’s hegemony accelerated the revival of the monarchy. Ironically, an institution strongly identified with the feudal order found itself reinvigorated in an age of new politics.
The association between papillary thyroid carcinoma and histologically proven Hashimoto's thyroiditis: a meta-analysis
Authors: Lee Ju-Han , Kim Younghye , Choi Jung-Woo , Kim Young-Sik 
Published: December 2012

ObjectiveNo consensus exists on the association between papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT). To resolve this controversy, this study aimed to evaluate the relationship between the two conditions using a meta-analysis.MethodsWe searched relevant published studies using citation databases including PubMed, Embase, and ISI Web of Science. The effect sizes of clinicopathologic parameters were calculated by odds ratio (OR), weighted mean difference, or hazard ratio (HR). The effect sizes were combined using a random-effects model.ResultsThirty-eight eligible studies including 10 648 PTC cases were selected. Histologically proven HT was identified in 2471 (23.2%) PTCs. HT was more frequently observed in PTCs than in benign thyroid diseases and other carcinomas (OR=2.8 and 2.4;P<0.001). PTCs with coexisting HT were significantly related to female patients (OR=2.7;P<0.001), multifocal involvement (OR=1.5;P=0.010), no extrathyroidal extension (OR=1.3;P=0.002), and no lymph node metastasis (OR=1.3;P=0.041). Moreover, PTCs with HT were significantly associated with long recurrence-free survival (HR=0.6;P=0.001).ConclusionsOur meta-analysis showed that PTC is significantly associated with pathologically confirmed HT. PTC patients with HT have favorable clinicopathologic characteristics compared with PTCs without HT. However, patients with HT need to be carefully monitored for the development of PTC.
Surface Plasmon Enhanced Photoluminescence in InAs Quantum Dots by Spherical Ag Nanoparticles
Authors: Mangham Scott C. , Wu Jiang , Lee Seungyong , Reddy Vanga R. , Manasreh Omar 
Published: December 2012

ABSTRACTReported is the photoluminescence enhancement due to surface plasmon from the metallic nanoparticles that are linked to the surface of a GaAs capped InAs quantum dots. In this study, spherical silver (Ag) nanoparticles are investigated where the different densities of Ag nanoparticles are deposited on four InAs/GaAs quantum dot samples. The PL enhancement due to Ag nanoparticles has been observed to be improved with increasing nanoparticle density. The photoluminescence enhancement is interpreted in terms of enhanced scattering from the surface plasmon excited in the Ag nanoparticles.
Depth Profiling of Cu(In,Ga)Se2 by Grazing Incidence X-ray Diffraction
Authors: Kötschau I.M. , Bilger G. , Schock H.W. 
Published: December 2012

AbstractGrazing incidence X-ray diffraction (GIXRD) in conjunction with a layer absorption modeling algorithm is a powerful tool for studying the structural properties of polycrystaline thin films. A typical application is the refinement of compositional depth profiles. Of genera interest are the depth profile of the Ga/(In+Ga)-ratio over the entire thickness of the thin film, as well as the depth profile of th Cu/(In+Ga)-ratio near the surface. In this respect the three stage process is a particular interesting deposition technique. A remarkable recrystalization of the entire thin film at the end of the second stage has a strong impact on Ga-gradients as well as on the Cu-depletion close to the surface. In this contribution we use the GIXRD technique to refine composititional depth profiles obtained by secondary ion mass spectrometry (SIMS). We demonstrate that structura changes near the surface due to the recrystalization can be monitored. In addition we are able measure the depth of a Cu-depleted surface layer with high accuracy.
Silicon Carbide Power Devices and Processing
Authors: Casady J.B. , Bonds J.R. , Draper W.A. , Merrett J.N. , Sankin I. , Seale D. , Mazzola M.S. 
Published: December 2012

AbstractAn overview of silicon carbide (SiC) power device technology is given with an emphasis on processing issues and commercial applications. Schottky Barrier Diodes (SBDs) were the first to be made commercially available in 2001, with power switch and RF amplifiers soon to follow. This paper discusses the performance of current available rectifiers and published power switch development and identifies key issues in processing and device structures which have influenced past and will impact future SiC product development.
Novel Glucose Biosensor Based on the Microcantilever
Authors: Pei Jianhong , Tian Fang , Thundat Thomas 
Published: December 2012

AbstractWe report a novel technique for micromechanical detection of biologically relevant glucose by immobilization of glucose oxidase (GOx) onto a microcantilever surface. Microfabricated cantilevers have recently attracted considerable interest in the development of a wide range of novel physical, chemical, and biological sensors. This paper describes the combination of this novel technology with enzyme specificity to construct a highly selective glucose biosensor. The enzyme-functionalized microcantilever undergoes bending due to a change in surface stress induced by the reaction between glucose and the GOx immobilized on the cantilever surface. The common interferents for glucose detection in other detection schemes have been tested and have shown no effect on the measurement of blood glucose level by this technique.