Volatile abundances and oxygen isotopes in basaltic to dacitic lavas on mid-ocean ridges: The role of assimilation at spreading centers

Most geochemical variability in MOR basalts is consistent with low- to moderate-pressure fractional crystallization of various mantle-derived parental melts. However, our geochemical data from MOR high-silica glasses, including new volatile and oxygen isotope data, suggest that assimilation of altered crustal material plays a significant role in the petrogenesis of dacites and may be important in the formation of basaltic lavas at MOR in general. MOR high-silica andesites and dacites from diverse areas show remarkably similar major element trends, incompatible trace element enrichments, and isotopic signatures suggesting similar processes control their chemistry. In particular, very high Cl and elevated H2O concentrations and relatively light oxygen isotope ratios (~5.8‰ vs. expected values of ~6.8‰) in fresh dacite glasses can be explained by contamination of magmas from a component of ocean crust altered by hydrothermal fluids. Crystallization of silicate phases and Fe-oxides causes an increase in δ18O in residual magma, but assimilation of material initially altered at high temperatures results in lower δ18O values. The observed geochemical signatures can be explained by extreme fractional crystallization of a MOR basalt parent combined with partial melting and assimilation (AFC) of amphibole-bearing altered oceanic crust. The MOR dacitic lavas do not appear to be simply the extrusive equivalent of oceanic plagiogranites. The combination of partial melting and assimilation produces a distinct geochemical signature that includes higher incompatible trace element abundances and distinct trace element ratios relative to those observed in plagiogranites. © 2011 Elsevier B.V

Accuracy and Reliability of Pallor for Detecting Anaemia: A Hospital-Based Diagnostic Accuracy Study

Anaemia is a common disorder. Most health providers in resource poor settings rely on physical signs to diagnose anaemia. We aimed to determine the diagnostic accuracy of pallor for anaemia by using haemoglobin as the reference standard.In May 2007, we enrolled consecutive patients over 12 years of age, able to consent and willing to participate and who had a haemoglobin measurement taken within a day of assessment of clinical pallor from outpatient and medicine inpatient department of a teaching hospital. We did a blind and independent comparison of physical signs (examination of conjunctivae, tongue, palms and nailbed for pallor) and the reference standard (haemoglobin estimation by an electronic cell counter). Diagnostic accuracy was measured by calculating likelihood ratio values and 95% confidence intervals (CI) at different haemoglobin thresholds and area under the receiver operating characteristic curve. Two observers examined a subset of patients (n = 128) to determine the inter-observer agreement, calculated by kappa statistics. We studied 390 patients (mean age 40.1 [SD 17.08] years); of whom 48% were women. The haemoglobin was <7 g/dL in 8% (95% confidence interval, 5, 10) patients; <9 g/dL in 21% (17, 26) patients and <12 g/dL in 64% (60, 70) patients. Among patients with haemoglobin <7 g/dL, presence of severe tongue pallor yielded a LR of 9.87 (2.81, 34.6) and its absence yielded a LR of 0. The tongue pallor outperformed other pallor sites and was also the best discriminator of anaemia at haemoglobin thresholds of 7 g/dL and 9 g/dL (area under the receiver operating characteristic curves (ROC area  = 0.84 [0.77, 0.90] and 0.71[0.64, 0.76]) respectively. The agreement between the two observers for detection of anaemia was poor (kappa values  = 0.07 for conjunctival pallor and 0.20 for tongue pallor).Clinical assessment of pallor can rule out and modestly rule in severe anaemia

Protracted timescales of lower crustal growth at the fast-spreading East Pacific Rise

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 5 (2012): 275-278, doi:10.1038/ngeo1378.Formation of the oceanic crust at mid-ocean ridges is a fundamental component of plate tectonics. A majority of the crust at many ridges is composed of plutonic rocks that form by crystallization of mantle-derived magmas within the crust. Recent application of U/Pb dating to samples from in-situ oceanic crust has begun to provide exciting new insight into the timing, duration and distribution of magmatism during formation of the plutonic crust1-4. Previous studies have focused on samples from slow-spreading ridges, however, the time scales and processes of crustal growth are expected to vary with plate spreading rate. Here we present the first high-precision dates from plutonic crust formed at the fast-spreading East Pacific Rise (EPR). Individual zircon minerals yielded dates from 1.420–1.271 million years ago, with uncertainties of ± 0.006–0.081 million years. Within individual samples, zircons record a range of dates of up to ~0.124 million years, consistent with protracted crystallization or assimilation of older zircons from adjacent rocks. The variability in dates is comparable to data from the Vema lithospheric section on the Mid-Atlantic Ridge (MAR)3, suggesting that time scales of magmatic processes in the lower crust may be similar at slow- and fast-spreading ridges.This research was partially funded by NSF grant OCE-0727914 (SAB), a Cardiff University International Collaboration Award (CJL) and NERC grant NE/C509023/1 (CJM).2012-07-2

Determining factors of thermoelectric properties of semiconductor nanowires

It is widely accepted that low dimensionality of semiconductor heterostructures and nanostructures can significantly improve their thermoelectric efficiency. However, what is less well understood is the precise role of electronic and lattice transport coefficients in the improvement. We differentiate and analyze the electronic and lattice contributions to the enhancement by using a nearly parameter-free theory of the thermoelectric properties of semiconductor nanowires. By combining molecular dynamics, density functional theory, and Boltzmann transport theory methods, we provide a complete picture for the competing factors of thermoelectric figure of merit. As an example, we study the thermoelectric properties of ZnO and Si nanowires. We find that the figure of merit can be increased as much as 30 times in 8-Å-diameter ZnO nanowires and 20 times in 12-Å-diameter Si nanowires, compared with the bulk. Decoupling of thermoelectric contributions reveals that the reduction of lattice thermal conductivity is the predominant factor in the improvement of thermoelectric properties in nanowires. While the lattice contribution to the efficiency enhancement consistently becomes larger with decreasing size of nanowires, the electronic contribution is relatively small in ZnO and disadvantageous in Si

BICEPP: an example-based statistical text mining method for predicting the binary characteristics of drugs

<p>Abstract</p> <p>Background</p> <p>The identification of drug characteristics is a clinically important task, but it requires much expert knowledge and consumes substantial resources. We have developed a statistical text-mining approach (BInary Characteristics Extractor and biomedical Properties Predictor: BICEPP) to help experts screen drugs that may have important clinical characteristics of interest.</p> <p>Results</p> <p>BICEPP first retrieves MEDLINE abstracts containing drug names, then selects tokens that best predict the list of drugs which represents the characteristic of interest. Machine learning is then used to classify drugs using a document frequency-based measure. Evaluation experiments were performed to validate BICEPP's performance on 484 characteristics of 857 drugs, identified from the Australian Medicines Handbook (AMH) and the PharmacoKinetic Interaction Screening (PKIS) database. Stratified cross-validations revealed that BICEPP was able to classify drugs into all 20 major therapeutic classes (100%) and 157 (of 197) minor drug classes (80%) with areas under the receiver operating characteristic curve (AUC) > 0.80. Similarly, AUC > 0.80 could be obtained in the classification of 173 (of 238) adverse events (73%), up to 12 (of 15) groups of clinically significant cytochrome P450 enzyme (CYP) inducers or inhibitors (80%), and up to 11 (of 14) groups of narrow therapeutic index drugs (79%). Interestingly, it was observed that the keywords used to describe a drug characteristic were not necessarily the most predictive ones for the classification task.</p> <p>Conclusions</p> <p>BICEPP has sufficient classification power to automatically distinguish a wide range of clinical properties of drugs. This may be used in pharmacovigilance applications to assist with rapid screening of large drug databases to identify important characteristics for further evaluation.</p

Distribution and Habitat Associations of Billfish and Swordfish Larvae across Mesoscale Features in the Gulf of Mexico

Ichthyoplankton surveys were conducted in surface waters of the northern Gulf of Mexico (NGoM) over a three-year period (2006–2008) to determine the relative value of this region as early life habitat of sailfish (Istiophorus platypterus), blue marlin (Makaira nigricans), white marlin (Kajikia albida), and swordfish (Xiphias gladius). Sailfish were the dominant billfish collected in summer surveys, and larvae were present at 37.5% of the stations sampled. Blue marlin and white marlin larvae were present at 25.0% and 4.6% of the stations sampled, respectively, while swordfish occurred at 17.2% of the stations. Areas of peak production were detected and maximum density estimates for sailfish (22.09 larvae 1000 m−2) were significantly higher than the three other species: blue marlin (9.62 larvae 1000 m−2), white marlin (5.44 larvae 1000 m−2), and swordfish (4.67 larvae 1000 m−2). The distribution and abundance of billfish and swordfish larvae varied spatially and temporally, and several environmental variables (sea surface temperature, salinity, sea surface height, distance to the Loop Current, current velocity, water depth, and Sargassum biomass) were deemed to be influential variables in generalized additive models (GAMs). Mesoscale features in the NGoM affected the distribution and abundance of billfish and swordfish larvae, with densities typically higher in frontal zones or areas proximal to the Loop Current. Habitat suitability of all four species was strongly linked to physicochemical attributes of the water masses they inhabited, and observed abundance was higher in slope waters with lower sea surface temperature and higher salinity. Our results highlight the value of the NGoM as early life habitat of billfishes and swordfish, and represent valuable baseline data for evaluating anthropogenic effects (i.e., Deepwater Horizon oil spill) on the Atlantic billfish and swordfish populations

Transcriptional Repressor Gfi1 Integrates Cytokine-Receptor Signals Controlling B-Cell Differentiation

Hematopoietic stem cell differentiation is specified by cytokines and transcription factors, but the mechanisms controlling instructive and permissive signalling networks are poorly understood. We provide evidence that CLP1-dependent IL7-receptor mediated B cell differentiation is critically controlled by the transcriptional repressor Gfi1. Gfi1-deficient progenitor B cells show global defects in IL7Rα-dependent signal cascades. Consequently, IL7-dependent trophic, proliferative and differentiation-inducing responses of progenitor B cells are perturbed. Gfi1 directly regulates expression levels of IL7Rα and indirectly controls STAT5 signalling via expression of SOCS3. Thus, Gfi1 selectively specifies IL7-dependent development of B cells from CLP1 progenitors, providing clues to the transcriptional networks integrating cytokine signals and lymphoid differentiation

Differential Epigenetic Regulation of TOX Subfamily High Mobility Group Box Genes in Lung and Breast Cancers

Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190) and 23% breast (n = 80) tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p<0.05). These transcripts were silenced in methylated lung and breast cancer cells and 5-Aza-2-deoxycytidine treatment re-expressed both. Extension of these assays to TOX, TOX3, and TOX4 genes that share similar genomic structure and protein homology with TOX2 revealed distinct methylation profiles by smoking status, histology, and cancer type. TOX was almost exclusively methylated in breast (43%) than lung (5%) cancer, whereas TOX3 was frequently methylated in lung (58%) than breast (30%) tumors. TOX4 was unmethylated in all samples and showed the highest expression in normal lung. Compared to TOX4, expression of TOX, TOX2 and TOX3 in normal lung was 25, 44, and 88% lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. Genome-wide assays revealed that siRNA-mediated TOX2 knockdown modulated multiple pathways while TOX3 inactivation targeted neuronal development and function. Although these knockdowns did not result in further phenotypic changes of lung cancer cells in vitro, the impact on tissue remodeling, inflammatory response, and cell differentiation pathways suggest a potential role for TOX2 in modulating tumor microenvironment

3D finite element electrical model of larval zebrafish ECG signals

Assessment of heart function in zebrafish larvae using electrocardiography (ECG) is a potentially useful tool in developing cardiac treatments and the assessment of drug therapies. In order to better understand how a measured ECG waveform is related to the structure of the heart, its position within the larva and the position of the electrodes, a 3D model of a 3 days post fertilisation (dpf) larval zebrafish was developed to simulate cardiac electrical activity and investigate the voltage distribution throughout the body. The geometry consisted of two main components; the zebrafish body was modelled as a homogeneous volume, while the heart was split into five distinct regions (sinoatrial region, atrial wall, atrioventricular band, ventricular wall and heart chambers). Similarly, the electrical model consisted of two parts with the body described by Laplace’s equation and the heart using a bidomain ionic model based upon the Fitzhugh-Nagumo equations. Each region of the heart was differentiated by action potential (AP) parameters and activation wave conduction velocities, which were fitted and scaled based on previously published experimental results. ECG measurements in vivo at different electrode recording positions were then compared to the model results. The model was able to simulate action potentials, wave propagation and all the major features (P wave, R wave, T wave) of the ECG, as well as polarity of the peaks observed at each position. This model was based upon our current understanding of the structure of the normal zebrafish larval heart. Further development would enable us to incorporate features associated with the diseased heart and hence assist in the interpretation of larval zebrafish ECGs in these conditions

Base-Pair Resolution DNA Methylation Sequencing Reveals Profoundly Divergent Epigenetic Landscapes in Acute Myeloid Leukemia

We have developed an enhanced form of reduced representation bisulfite sequencing with extended genomic coverage, which resulted in greater capture of DNA methylation information of regions lying outside of traditional CpG islands. Applying this method to primary human bone marrow specimens from patients with Acute Myelogeneous Leukemia (AML), we demonstrated that genetically distinct AML subtypes display diametrically opposed DNA methylation patterns. As compared to normal controls, we observed widespread hypermethylation in IDH mutant AMLs, preferentially targeting promoter regions and CpG islands neighboring the transcription start sites of genes. In contrast, AMLs harboring translocations affecting the MLL gene displayed extensive loss of methylation of an almost mutually exclusive set of CpGs, which instead affected introns and distal intergenic CpG islands and shores. When analyzed in conjunction with gene expression profiles, it became apparent that these specific patterns of DNA methylation result in differing roles in gene expression regulation. However, despite this subtype-specific DNA methylation patterning, a much smaller set of CpG sites are consistently affected in both AML subtypes. Most CpG sites in this common core of aberrantly methylated CpGs were hypermethylated in both AML subtypes. Therefore, aberrant DNA methylation patterns in AML do not occur in a stereotypical manner but rather are highly specific and associated with specific driving genetic lesions