Microdosimetry radiation analysis method and device

Apparatus and method for qualitatively and quantitatively analyzing a complex radiation field are provided. A microdosimetry device is provided having an array of microstructure parallel p-n junctions. Each junction defines a predetermined sensitive volume within which a voltage pulse is produced responsive to incident radiation. Circuitry in communication with the detector array generates digital pulse signals representative of the voltage pulses induced within the sensitive volumes responsive to incident radiation, and further provides a summation of the digital pulses occurring at particular energies. The summations of digital pulses are compared to known energies generated by known ionizing particles in comparable sensitive volumes to generate an dose equivalent estimate. Apparatus and method for calculating the total dose from an incident radiation field may also be included

Inter and intra-specific diversity of parasites that cause lymphatic filariasis

AbstractLymphatic filariasis is caused by three closely related nematode parasites: Wuchereria bancrofti, Brugia malayi and Brugia timori. These species have many ecological variants that differ in several aspects of their biology such as mosquito vector species, host range, periodicity, and morphology. Although the genome of B. malayi (the first genome sequenced from a parasitic nematode) has been available for more than five years, very little is known about genetic variability among the lymphatic dwelling filariae. The genetic diversity among these worms is not only interesting from a biological perspective, but it may have important practical implications for the Global Program to Eliminate Lymphatic Filariasis, as the parasites may respond differently to diagnostic tests and/or medical interventions. Therefore, better information on their genetic variability is urgently needed. With improved methods for nucleic acid extraction and recent advances in sequencing chemistry and instrumentation, this gap can be filled relatively inexpensively. Improved information on filarial genetic diversity may increase the chances of success for lymphatic filariasis elimination programs

Passive solid state microdosimeter with electronic readout

Apparatus and method for qualitatively and quantitatively analyzing a complex radiation field are provided. A passive microdosimetry detector device records the energy deposition of incident radiation using an array of microstructure non-volatile memory devices. Each microstructure non-volatile memory device is capable of storing a predetermined initial charge without requiring a power source. A radiation particle incident to a microstructure non-volatile memory device is termed an event . Each such event may generate a charge within a sensitive volume defined by the microstructure non-volatile memory device. The charge generated within the sensitive volume alters the stored initial charge by an amount falling within a range corresponding to the energy deposited by certain particle types. Data corresponding to such charge alterations for a plurality of microstructure non-volatile memory devices within an array of such devices are presented to a qualitative analyzing device. The qualitative analyzing device converts the data to a spectral analysis of the incident radiation field by applying ICRP-recommended weighting factors to individual events or approximations thereof

Localization of Wolbachia-like gene transcripts and peptides in adult Onchocerca flexuosa worms indicates tissue specific expression

BACKGROUND: Most filarial species in the genus Onchocerca depend on Wolbachia endobacteria to successfully carry out their life cycle. O. flexuosa is a Wolbachia-free species, but its genome contains Wolbachia-like sequences presumably obtained from Wolbachia via horizontal gene transfer. Proteogenomic studies have shown that many of these Wolbachia-like sequences are expressed in adult worms. METHODS: Six Wolbachia-like sequences in O. flexuosa were chosen for further study based on their sequence conservation with Wolbachia genes, length of predicted open reading frames, and expression at the RNA and/or protein levels. In situ hybridization and immunohistochemical labeling were used to localize Wolbachia-like transcripts and peptides in adult worm tissues. RESULTS: RNA probes representing three of the six target sequences produced hybridization signals in worm tissues. These probes bound to transcripts in the intestine and lateral chords of both sexes, in the hypodermis, median chords and uteri in females, and in sperm precursor cells in males. Antibodies raised to three peptides corresponding to these transcripts bound to specific bands in a soluble extract of adult O. flexuosa by Western blot that were not labeled by control antibodies in pre-immune serum. Two of the three antibodies produced labeling patterns in adult worm sections that were similar to those of the RNA probes, while the third produced a different pattern. CONCLUSIONS: A subset of the Wolbachia-like sequences present in the genome of the Wolbachia-free filarial species O. flexuosa are transcribed in tissues where Wolbachia reside in infected filarial species. Some of the peptides and/or proteins derived from these transcripts appear to be concentrated in the same tissues while others may be exported to other regions of the worm. These results suggest that horizontally transferred Wolbachia genes and gene products may replicate important Wolbachia functions in uninfected filarial worms

Systems biology studies of adult Paragonimus lung flukes facilitate the identification of immunodominant parasite antigens

Paragonimiasis is a food-borne trematode infection acquired by eating raw or undercooked crustaceans. It is a major public health problem in the far East, but it also occurs in South Asia, Africa, and in the Americas. Paragonimus worms cause chronic lung disease with cough, fever and hemoptysis that can be confused with tuberculosis or other non-parasitic diseases. Treatment is straightforward, but diagnosis is often delayed due to a lack of reliable parasitological or serodiagnostic tests. Hence, the purpose of this study was to use a systems biology approach to identify key parasite proteins that may be useful for development of improved diagnostic tests.The transcriptome of adult Paragonimus kellicotti was sequenced with Illumina technology. Raw reads were pre-processed and assembled into 78,674 unique transcripts derived from 54,622 genetic loci, and 77,123 unique protein translations were predicted. A total of 2,555 predicted proteins (from 1,863 genetic loci) were verified by mass spectrometric analysis of total worm homogenate, including 63 proteins lacking homology to previously characterized sequences. Parasite proteins encoded by 321 transcripts (227 genetic loci) were reactive with antibodies from infected patients, as demonstrated by immunoaffinity purification and high-resolution liquid chromatography-mass spectrometry. Serodiagnostic candidates were prioritized based on several criteria, especially low conservation with proteins in other trematodes. Cysteine proteases, MFP6 proteins and myoglobins were abundant among the immunoreactive proteins, and these warrant further study as diagnostic candidates.The transcriptome, proteome and immunolome of adult P. kellicotti represent a major advance in the study of Paragonimus species. These data provide a powerful foundation for translational research to develop improved diagnostic tests. Similar integrated approaches may be useful for identifying novel targets for drugs and vaccines in the future

Comparing the mitochondrial genomes of Wolbachia-dependent and independent filarial nematode species

BACKGROUND: Many species of filarial nematodes depend on Wolbachia endobacteria to carry out their life cycle. Other species are naturally Wolbachia-free. The biological mechanisms underpinning Wolbachia-dependence and independence in filarial nematodes are not known. Previous studies have indicated that Wolbachia have an impact on mitochondrial gene expression, which may suggest a role in energy metabolism. If Wolbachia can supplement host energy metabolism, reduced mitochondrial function in infected filarial species may account for Wolbachia-dependence. Wolbachia also have a strong influence on mitochondrial evolution due to vertical co-transmission. This could drive alterations in mitochondrial genome sequence in infected species. Comparisons between the mitochondrial genome sequences of Wolbachia-dependent and independent filarial worms may reveal differences indicative of altered mitochondrial function. RESULTS: The mitochondrial genomes of 5 species of filarial nematodes, Acanthocheilonema viteae, Chandlerella quiscali, Loa loa, Onchocerca flexuosa, and Wuchereria bancrofti, were sequenced, annotated and compared with available mitochondrial genome sequences from Brugia malayi, Dirofilaria immitis, Onchocerca volvulus and Setaria digitata. B. malayi, D. immitis, O. volvulus and W. bancrofti are Wolbachia-dependent while A. viteae, C. quiscali, L. loa, O. flexuosa and S. digitata are Wolbachia-free. The 9 mitochondrial genomes were similar in size and AT content and encoded the same 12 protein-coding genes, 22 tRNAs and 2 rRNAs. Synteny was perfectly preserved in all species except C. quiscali, which had a different order for 5 tRNA genes. Protein-coding genes were expressed at the RNA level in all examined species. In phylogenetic trees based on mitochondrial protein-coding sequences, species did not cluster according to Wolbachia dependence. CONCLUSIONS: Thus far, no discernable differences were detected between the mitochondrial genome sequences of Wolbachia-dependent and independent species. Additional research will be needed to determine whether mitochondria from Wolbachia-dependent filarial species show reduced function in comparison to the mitochondria of Wolbachia-independent species despite their sequence-level similarities

Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial.

Importance: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. Objective: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. Design, Setting, and Participants: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF ( Interventions: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. Main Outcomes and Measures: The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). Results: Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P \u3e .05. Conclusions and Relevance: Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. Trial Registration: clinicaltrials.gov Identifier: NCT02188784

Solution processed ZnO homogeneous quasisuperlattice materials

Heterogeneous multilayered oxide channel materials have enabled low temperature, high mobility thin film transistor technology by solution processing. The authors report the growth and characterization of solution-based, highly uniform and c-axis orientated zinc oxide (ZnO) single and multilayered thin films. Quasisuperlattice (QSL) metal oxide thin films are deposited by spin-coating and the structural, morphological, optical, electronic, and crystallographic properties are investigated. In this work, the authors show that uniform, coherent multilayers of ZnO can be produced from liquid precursors using an iterative coating-drying technique that shows epitaxial-like growth on SiO2, at a maximum temperature of 300 °C in air. As QSL films are grown with a greater number of constituent layers, the crystal growth direction changes from m-plane to c-plane, confirmed by x-ray and electron diffraction. The film surface is smooth for all QSLs with root mean square roughness <0.14 nm. X-ray photoelectron spectroscopy (XPS) and photoluminescence (PL) of electronic defects in the QSL structure show a dependence of defect emission on the QSL thickness, and PL mapping demonstrates that the defect signature is consistent across the QSL film in each case. XPS and valence-band analysis shown a remarkably consistent surface composition and electronic structure during the annealing process developed here

Highly-ordered growth of solution-processable ZnO for thin film transistors

We demonstrate that crystalline, epitaxial-like and highly ordered ZnO thin films and quasi-superlattice structures can be achieved from a precursor liquid at relatively low temperature via spin-coating. The synthesised films are smooth, stoichiometric ZnO with controllable thickness. An iterative layer-by-layer coating schematic is employed to demonstrate the effects of film thickness on structure, morphology as well as the surface and internal defects. Characterisation of the crystallinity, morphology, O-vacancy formation, stoichiometry, surface roughness and thickness variation was determined through X-ray diffraction, scanning and transmission electron and atomic force microscopy, X-ray photoelectron and photoluminescence spectroscopy. We demonstrate that iterative spin-coating of deposited ZnO films results in a transition in crystal texture with increasing thickness (number of layers) from the [ ] m-plane to the [ ] c-plane. The films attain a c-axis preferential orientation, with no other crystalline peaks present. Results show that the film’s surface morphology was very smooth, with average rms roughness <0.15 nm. Examination of these films also shows the consistency of the surface composition and defect level while highlighting the effect of temperature and cumulative annealing condition on the internal defect concentration

Optical reflectivity of spin-coated multilayered ZnO and Al:ZnO Thin Films

Controlling growth, doping, crystallization, thickness of thin films of thin film transistor (TFT) channel materials is required in order to improve and control physical properties, primarily electronic conductivity and optical transparency. With the advent of flexible electronics and curved TFT-based display panels, low cost, solution-processed methods are important and provide scalable coating methods on a range of substrates. This work demonstrates the changes to the morphology, crystalline structure, optical reflectivity and electrical conductance of solution-processed ZnO thin films by the inclusion of an aluminium dopant during spin-coating. The measurements also determine the compositional chemical state of the Al:ZnO structures compared to ZnO using X-ray photoelectron spectroscopy in conjunction with detailed X-ray diffraction and transmission electron microscopy examination of the film morphology