bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral prion disease pathogenesis is unaltered in the absence of sialoadhesin (Siglec‐1/CD169)
Authors: Bradford Barry M. , Crocker Paul R. , Mabbott Neil A.
Published: March 2014

Prions are a unique group of pathogens, which are considered to comprise solely of an abnormally folded isoform of the cellular prion protein. The accumulation and replication of prions within secondary lymphoid organs is important for their efficient spread from the periphery to the brain where they ultimately cause neurodegeneration and death. Mononuclear phagocytes (MNP) play key roles in prion disease pathogenesis. Some MNP appear to facilitate the propagation of prions to and within lymphoid tissues, whereas others may aid their clearance by phagocytosis and by destroying them. Our recent data show that an intact splenic marginal zone is important for the efficient delivery of prions into the B‐cell follicles where they subsequently replicate upon follicular dendritic cells before infecting the nervous system. Sialoadhesin is an MNP‐restricted cell adhesion molecule that binds sialylated glycoproteins. Sialoadhesin is constitutively expressed upon splenic marginal zone metallophilic and lymph node sub‐capsular sinus macrophage populations, where it may function to bind sialylated glycoproteins, pathogens and exosomes in the blood and lymph via recognition of terminal sialic acid residues. As the prion glycoprotein is highly sialylated, we tested the hypothesis that sialoadhesin may influence prion disease pathogenesis. We show that after peripheral exposure, prion pathogenesis was unaltered in sialoadhesin‐deficient mice; revealing that lymphoid sequestration of prions is not mediated via sialoadhesin. Hence, although an intact marginal zone is important for the efficient uptake and delivery of prions into the B‐cell follicles of the spleen, this is not influenced by sialoadhesin expression by the MNP within it.
Accumulation of functionally immature myeloid dendritic cells in lymph nodes of rhesus macaques with acute pathogenic simian immunodeficiency virus infection
Authors: Wijewardana Viskam , Bouwer Anthea L. , Brown Kevin N. , Liu Xiangdong , Barratt‐Boyes Simon M.
Published: March 2014

Myeloid dendritic cells (mDC) are key mediators of innate and adaptive immunity to virus infection, but the impact of HIV infection on the mDC response, particularly early in acute infection, is ill‐defined. We studied acute pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques to address this question. The mDC in blood and bone marrow were depleted within 12 days of intravenous infection with SIVmac251, associated with a marked proliferative response. In lymph nodes, mDC were apoptotic, activated and proliferating, despite normal mDC numbers, reflecting a regenerative response that compensated for mDC loss. Blood mDC had increased expression of MHC class II, CCR7 and CD40, whereas in lymph nodes these markers were significantly decreased, indicating that acute infection induced maturation of mDC in blood but resulted in accumulation of immature mDC in lymph nodes. Following SIV infection, lymph node mDC had an increased capacity to secrete tumour necrosis factor‐α upon engagement with a Toll‐like receptor 7/8 ligand that mimics exposure to viral RNA, and this was inversely correlated with MHC class II and CCR7 expression. Lymph node mDC had an increased ability to capture and cleave soluble antigen, confirming their functionally immature state. These data indicate that acute SIV infection results in increased mDC turnover, leading to accumulation in lymph nodes of immature mDC with an increased responsiveness to virus stimulation.
North‐African house martins endure greater haemosporidian infection than their European counterparts
Authors: van Rooyen Juan , Jenkins Tania , Lahlah Naouel , Christe Philippe
Published: March 2014

Afro‐Palearctic migrant species are exposed to parasites at both breeding and over‐wintering grounds. The house martin Delichon urbicum is one such migratory species facing high instances of blood parasite infection. In an attempt to determine whether breeding European house martins harbour similar blood parasite communities to populations breeding in North Africa, birds were sampled at their breeding grounds in Switzerland and Algeria. Moreover, haemosporidian prevalence and parasite communities were compared to published data sets on Spanish and Dutch breeding populations. This study furthermore wanted to establish whether co‐infection with multiple genera or lineages of parasites had negative eﬀects on host body condition. Breeding house martins caught in Algeria showed a higher prevalence of avian haemosporidian parasites than did European populations. Swiss house martins showed a prevalence comparable to that of Spanish and Dutch populations. There were slight differences in the haemosporidian community between European and North‐African populations in terms of composition and abundance of each lineage. Similar to the Dutch house martins, but in contrast to the Spanish population, infection status and number of genera of parasites infecting single hosts did not inﬂuence Swiss house martin body condition.
West to east dispersal in a widespread animal‐dispersed woody angiosperm genus (Aglaia, Meliaceae) across the Indo‐Australian Archipelago
Authors: Grudinski Melanie , Wanntorp Livia , Pannell Caroline M. , Muellner‐Riehl Alexandra Nora
Published: March 2014

Aim

Despite increasing scientific interest in the Indo‐Australian Archipelago (IAA), this geographically complex region, hosting an outstanding level of marine and terrestrial biodiversity, remains only partly understood biogeographically. We present an updated and resolved phylogenetic tree for the woody genus Aglaia, and we investigate the origin and dispersal history of Aglaia.

Location

Australasia, Indo‐Australian Archipelago, Indomalesia, Pacific islands.

Methods

Sequence data from the nuclear ribosomal internal transcribed spacers (ITS) were used to reconstruct the phylogenetic relationships of 182 taxa. The phylogeny was then used in combination with fossil data and secondary calibration information to estimate divergence times using a relaxed molecular clock approach. Biogeographical scenarios and potential ancestral areas were investigated using statistical dispersal–vicariance analysis (S‐DIVA) and the dispersal–extinction–cladogenesis (DEC) method.

Results

Our study showed that the crown group of Aglaia dates back to the Oligocene/Miocene boundary (c. 23.0 Ma), with major divergence events beginning in the middle Miocene (c. 13.8 Ma). Sundaland was confirmed as the area of origin of modern Aglaia. The results further provided evidence that dispersal routes existed between the Sunda Shelf and Wallacea and further east to the Pacific islands, crossing both Wallace's and Lydekker's lines.

Main conclusions

The directionality of dispersal events to or across Wallacea was predominantly eastwards, following the expansion of wet tropical forest across Wallace's Line and beyond. However, several reversal dispersal events occurred as well. During the Pleistocene (0.1–2.6 Ma) there were long‐distance dispersal events from the western Pacific islands back to Sundaland or the Philippines, which might have been facilitated by birds. In summary, our study confirms that Aglaia had a Sundanian origin and started to disperse eastwards during the Miocene (5.3–23.0 Ma), with limited dispersal across Lydekker's Line. The comparison of the age of clades with the proposed age of their areas of distribution based on independent geological evidence showed good temporal agreement.
A Distinct Subpopulation of Cauliflower mosaic virus (CaMV) in South Iran
Authors: Farzadfar Shirin , Pourrahim Reza
Published: March 2014

Cauliflower mosaic virus (CaMV) with a high incidence and widespread distribution on Brassica crops in Iran reduces the yield and quality of these crops. The complete sequences of three open reading frames (ORFs) 2, 4 and 6 coding for aphid transmission (AT), coat protein (CP) and inclusion body protein/translation transactivator (TAV) genes, respectively, were determined for two Iranian CaMV isolates from Kerman (south Iran). They induced latent or mild mottle (L/MMo) infection in Brassica oleracea var. capitata so are considered as the (L/MMo) biotype. Clear recombination breakpoints were detected between ORF2 and ORF6 in two Kerman isolates using concatenate fragments. Phylogenetic analysis revealed three Iranian CaMV subpopulations in which the two Kerman isolates in the new subgroup C were added to the two previously reported Iranian subpopulations A (central and west Iran) and B (north‐east Iran). Also three regions of pairwise identity were detected which representing: 97.1–100, 93.8–97.1 and 90.6–93.8% for subgroups A, C and B, respectively. Our analysis showed the high variability of Iranian CaMV population and provided valuable new information for understanding the diversity and evolution of caulimoviruses. Furthermore, star phylogeny was found in the subgroup C with overall lack of nt diversity and high haplotype diversity as evidence of a recent population expansion after a genetic bottleneck although this may have been modified subsequently by clinal genetic drift. The appearance of new genetic types demonstrates a high potential of risks and should be considered in the planning of efficient control programmes.
Mode of Action and Genetic Analysis of Resistance to Fluazinam in Ustilago maydis
Authors: Vitoratos Andrew G.
Published: March 2014

Ustilago maydis strains, with low to moderate resistance to fluazinam (Rf ranging from 11.8 to 80), were isolated in a mutation frequency of 0.75 × 10−7 after chemical mutagenesis with N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG). Genetic analysis resulted in the identification of two chromosomal genes. A study of the effect of mutant genes in the phytopathogenic fitness of U. maydis revealed that the resistance mutations had no apparent effect on mycelia growth rate and pathogenicity on young corn plants. Cross‐resistant studies showed that the mutations for resistance to fluazinam were also responsible for resistance to oligomycin, but not to dinitrophenol. A dose‐dependent inhibition of glucose oxidation in whole cells was observed by both fluazinam and oligomycin, and a complete inhibition was found at 40 μg/ml. The results obtained provide strong evidence that the mode of action of fluazinam consists of the inhibition the fungal cell's energy production process through direct inhibition of the ATP synthetase.
The pharmacokinetics of a single oral or rectal dose of concurrently administered isoniazid, rifampin, pyrazinamide, and ethambutol in Asian elephants (Elephas maximus)
Authors: P. Brock A. , Isaza R. , Egelund E. F. , Hunter R. P. , Peloquin C. A.
Published: March 2014

Tuberculosis, caused by Mycobacterium tuberculosis, is a disease of concern in captive Asian elephants (Elephas maximus). Treatment for tuberculosis in elephants utilizes multidrug protocols combining isoniazid, rifampin, pyrazinamide, and/or ethambutol. In this study, a single, coformulated dose of isoniazid 5 mg/kg, rifampin 10 mg/kg, pyrazinamide 30 mg/kg, and ethambutol 30 mg/kg was administered orally to six Asian elephants, and rectally to five elephants using a cross‐over design. Blood samples were collected serially over 24 h. Pyrazinamide and ethambutol concentrations were determined using validated gas chromatography assays. Isoniazid and rifampin concentrations were determined using validated high‐performance liquid chromatography assays. Rectal isoniazid produced an earlier Tmax compared with oral administration. Oral isoniazid resulted in a comparatively lower Cmax, but higher AUC values compared with rectal isoniazid. Oral rifampin and oral ethambutol were well absorbed while rectal rifampin was not. Oral pyrazinamide produced comparatively higher Cmax and AUC values compared with rectal pyrazinamide. Results of this study indicate that currently recommended therapeutic monitoring sample collection times for rectal isoniazid and oral rifampin do not provide an accurate assessment of exposure for these drugs. This study demonstrates notable individual variability, indicating that dosing of these medications requires individual monitoring and provides additional information to guide the clinician when treating elephants.
Geochemical zoning and magnetic mineralogy at Fe,Ni‐alloy–troilite interfaces of three iron meteorites from Morasko, Coahuila II, and Mundrabilla
Authors: Luecke W. , Kontny A. , Kramar U.
Published: March 2014

We combined high‐resolution and space‐resolved elemental distribution with investigations of magnetic minerals across Fe,Ni‐alloy and troilite interfaces for two nonmagmatic (Morasko and Mundrabilla) IAB group iron meteorites and an octahedrite found in 1993 in Coahuila/Mexico (Coahuila II) preliminarily classified on Ir and Au content as IIAB group. The aim of this study was to elucidate the crystallization and thermal history using gradients of the siderophile elements Ni, Co, Ge, and Ga and the chalcophile elements Cr, Cu, and Se with a focus on magnetic minerals. The Morasko and Coahuila II meteorite show a several mm‐thick carbon‐ and phosphorous‐rich transition zone between Fe,Ni‐alloy and troilite, which is characterized by magnetic cohenite and nonmagnetic or magnetic schreibersite. At Morasko, these phases have a characteristic trace element composition with Mo enriched in cohenite. In both Morasko and Coahuila II, Ni is enriched in schreibersite. The minerals have crystallized from immiscible melts, either by fractional crystallization and C‐ and P‐enrichment in the melt, or by partial melting at temperatures slightly above the eutectic point. During crystallization of Mundrabilla, the field of immiscibility was not reached. Independent of meteorite group and cooling history, the magnetic mineralogy (daubreelite, cohenite and/or schreibersite, magnetite) is very similar to the troilite (and transition zone) for all three investigated iron meteorites. If these minerals can be separated from the metal, they might provide important information about the early solar system magnetic field. Magnetite is interpreted as a partial melting or a terrestrial weathering product of the Fe,Ni‐alloy under oxidizing conditions.
Aromatase and regulation of the estrogen‐to‐androgen ratio in synovial tissue inflammation: common pathway in both sexes
Authors: Capellino Silvia , Straub Rainer H. , Cutolo Maurizio
Published: March 2014

Sex hormones play an active role in inflammatory responses, with androgens being anti‐inflammatory, whereas estrogens have both pro‐ and anti‐inflammatory effects. In rheumatoid arthritis (RA) patients, low levels of androgens and high levels of estrone are found in the synovial fluid. Aromatase is the key enzyme for the conversion of androgens into estrogens. Proinflammatory cytokines stimulate aromatase activity so that the inflammatory milieu can induce conversion of androgens to estrogens. Moreover, testosterone inhibits aromatase activity. As local androgen levels are low in RA, this can contribute to high aromatase activity in the synovium. Importantly, aromatase‐converted estrogens are converted into proproliferative and proinflammatory 16‐hydroxylated estrogens. A hormone involved in aromatase activity is vitamin D, which downregulates aromatase in human RA macrophages. Collectively, evidence suggests a key role of aromatase in sex hormone balance during chronic inflammation and points to the importance of vitamin D as a possible new tool for aromatase modulation.
Influence of inherited topography on gravitational slope failure: three‐dimensional numerical modelling of the La Clapière slope, Alpes‐Maritimes, France
Authors: Bois Thomas , Tric Emmanuel , Lebourg Thomas
Published: March 2014

Gravitational slope failure involves rock slopes at various scales. Nowadays, it is accepted that different factors influence slope destabilization, including topography. In many cases, slope failure occurs between tributary valleys cutting the slope. In this study, we ask what influence tributary valleys have on slope failure. To tackle this question, we developed a 3‐D numerical model of the La Clapière Slope and then examined a series of simplified 3‐D models with different geometries of tributary valleys (spacing and depth). Our results show that: (1) whatever considered in situ stresses are, including the third dimension reduces the destabilization threshold compared with 2‐D models; and (2) the spacing and the depth of tributary valleys influence slope failure. For shallow incisions, increasing the lateral spacing between tributary valleys does not affect failure localization but does increase slope damage (to a stable value from 2000 m). However, deeper incision does not affect slope damage but does contribute to failure localization. When the spacing is less than 1500 m, the part of the slope between tributary valleys is not involved in the failure process, but for spacings above 1500 m slope failure occurs between tributary valleys.
Apple MdABCF assists in the transportation of S‐RNase into pollen tubes
Authors: Meng Dong , Gu Zhaoyu , Li Wei , Wang Aide , Yuan Hui , Yang Qing , Li Tianzhong
Published: March 2014

Self‐incompatibility (SI) is a reproductive isolation mechanism in flowering plants. Plants in the Solanaceae, Rosaceae and Plantaginaceae belong to the gametophytic self‐incompatibility type. S‐RNase, which is encoded by a female‐specific gene located at the S locus, degrades RNA in the pollen tube and causes SI. Recent studies have provided evidence that S‐RNase is transported non‐selectively into the pollen tube, but have not specified how this transportation is accomplished. We show here that the apple (Malus domestica) MdABCF protein, which belongs to group F of the ABC transporter family, assists in transportation of S‐RNase into the pollen tube. MdABCF is located in the pollen tube membrane and interacts with S‐RNase. S‐RNase was unable to enter the pollen tube when MdABCF was silenced by antisense oligonucleotide transfection. Our results show that MdABCF assists in transportation of either self or non‐self S‐RNase into the pollen tube. Moreover, MdABCF coordinates with the cytoskeleton to transport S‐RNase. Blockage of S‐RNase transport disrupts self‐incompatibility in this system.
Higher Chow cycles on Abelian surfaces and a non-Archimedean analogue of the Hodge--conjecture
Authors: Sreekantan Ramesh
Published: March 2014

We construct new indecomposable elements in the higher Chow group $CH^2(A,1)$ of a principally polarized Abelian surface over a $p$-adic local field, which generalize an element constructed by Collino [Griffiths’ infinitesimal invariant and higher K-theory on hyperelliptic Jacobians, J. Algebraic Geom. 6 (1997), 393–415]. These elements are constructed using a generalization, due to Birkenhake and Wilhelm [Humbert surfaces and the Kummer plane, Trans. Amer. Math. Soc. 355 (2003), 1819–1841 (electronic)], of a classical construction of Humbert. They can be used to prove a non-Archimedean analogue of the Hodge-${\mathcal{D}}$-conjecture – namely, the surjectivity of the boundary map in the localization sequence – in the case where the Abelian surface has good and ordinary reduction.
Effects of a sucrose‐enriched diet on the pattern of gene expression, contraction and Ca2+ transport in Goto–Kakizaki type 2 diabetic rat heart
Authors: Gaber E. M. , Jayaprakash P. , Qureshi M. A. , Parekh K. , Oz M. , Adrian T. E. , Howarth F. C.
Published: March 2014

New Findings

What is the central question of this study?

Poor diet is a risk factor for development of type 2 diabetes mellitus and its associated complications. In this study, the effects of sucrose‐enriched diet on the pattern of gene expression, contraction and Ca2+ transport in type 2 diabetic heart are explored.

What is the main finding and its importance?

The altered pattern of gene expression in type 2 diabetic hearts was further altered in diabetic and control rats that received a sucrose‐enriched diet, and these alterations were associated with changes in ventricular myocyte shortening and Ca2+ transport.

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM), and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar‐sweetened beverages has been linked to rising rates of obesity, which in turn is a risk factor for development of T2DM. In this study, the effects of a sucrose‐enriched diet on the pattern of gene expression, contraction and Ca2+ transport in the Goto–Kakizaki T2DM rat heart were investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3 and Mylpf), intercellular proteins (Gja4), cell membrane transport (Atp1b1), calcium channels (Cacna1c, Cacna1g and Cacnb1) and potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared with control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3 and Tnn2), intercellular proteins (Gja1 and Gja4), intracellular Ca2+ transport (Atp2a1 and Ryr2), cell membrane transport (Atp1a2 and Atp1b1) and potassium channel proteins (Kcnj2 and Kcnj8) were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in control rats fed sucrose compared with control rats. Genes encoding cardiac muscle proteins (Myh7) and potassium channel proteins (Kcnj11) were downregulated in control and GK rats fed sucrose compared with control and GK rats, respectively. The amplitude of shortening was reduced in myocytes from the control–sucrose group compared with control rats and in the GK–sucrose group compared with GK rats. The amplitude of the Ca2+ transient was increased in myocytes from control–sucrose compared with control rats and decreased in GK–sucrose compared with GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intracellular Ca2+ transport in ventricular myocytes from GK T2DM and control rats fed a sucrose‐enriched diet.
Cartilage Nominal Strain Correlates With Shear Modulus and Glycosaminoglycans Content in Meniscectomized Joints
Authors: Song Yongnam , Carter Dennis R. , Giori Nicholas J.
Published: March 2014

Postmeniscectomy osteoarthritis (OA) is hypothesized to be the consequence of abnormal mechanical conditions, but the relationship between postsurgical alterations in articular cartilage strain and in vivo biomechanical/biochemical changes in articular cartilage is unclear. We hypothesized that spatial variations in cartilage nominal strain (percentile thickness change) would correlate with previously reported in vivo articular cartilage property changes following meniscectomy. Cadevaric sheep knees were loaded in cyclic compression which was previously developed to mimic normal sheep gait, while a 4.7 T magnetic resonance imaging (MRI) imaged the whole joint. 3D cartilage strain maps were compared with in vivo sheep studies that described postmeniscectomy changes in shear modulus, phase lag, proteoglycan content and collagen organization/content in the articular cartilage. The area of articular cartilage experiencing high (overloaded) and low (underloaded) strain was significantly increased in the meniscectomized tibial compartment by 10% and 25%, respectively, while no significant changes were found in the nonmeniscectomized compartment. The overloaded and underloaded regions of articular cartilage in our in vitro specimens correlated with regions of in vivo shear modulus reduction. Glycosaminoglycans (GAG) content only increased at the underloaded articular cartilage but decreased at the overloaded articular cartilage. No significant correlation was found in phase lag and collagen organization/content changes with the strain variation. Comparisons between postsurgical nominal strain and in vivo cartilage property changes suggest that both overloading and underloading after meniscectomy may directly damage the cartilage matrix stiffness (shear modulus). Disruption of superficial cartilage by overloading might be responsible for the proteoglycan (GAG) loss in the early stage of postmeniscectomy OA.
ZrN coatings deposited by high power impulse magnetron sputtering and cathodic arc techniques
Authors: Purandare Yashodhan , Ehiasarian Arutiun , Santana Antonio , Hovsepian Papken
Published: March 2014

Zirconium nitride (ZrN) coatings were deposited on 1 μm finish high speed steel and 316L stainless steel test coupons. Cathodic Arc (CA) and High Power Impulse Magnetron Sputtering (HIPIMS) + Unbalanced Magnetron Sputtering (UBM) techniques were utilized to deposit coatings. CA plasmas are known to be rich in metal and gas ions of the depositing species as well as macroparticles (droplets) emitted from the arc sports. Combining HIPIMS technique with UBM in the same deposition process facilitated increased ion bombardment on the depositing species during coating growth maintaining high deposition rate. Prior to coating deposition, substrates were pretreated with Zr+ rich plasma, for both arc deposited and HIPIMS deposited coatings, which led to a very high scratch adhesion value (LC2) of 100 N. Characterization results revealed the overall thickness of the coatings in the range of 2.5 μm with hardness in the range of 30–40 GPa depending on the deposition technique. Cross-sectional transmission electron microscopy and tribological experiments such as dry sliding wear tests and corrosion studies have been utilized to study the effects of ion bombardment on the structure and properties of these coatings. In all the cases, HIPIMS assisted UBM deposited coating fared equal or better than the arc deposited coatings, the reasons being discussed in this paper. Thus H+U coatings provide a good alternative to arc deposited where smooth, dense coatings are required and macrodroplets cannot be tolerated.
Experimental validation of a kilovoltage x‐ray source model for computing imaging dose
Authors: Poirier Yannick , Kouznetsov Alexei , Koger Brandon , Tambasco Mauro
Published: March 2014

Purpose:

To introduce and validate a kilovoltage (kV) x‐ray source model and characterization method to compute absorbed dose accrued from kV x‐rays.

Methods:

The authors propose a simplified virtual point source model and characterization method for a kV x‐ray source. The source is modeled by: (1) characterizing the spatial spectral and fluence distributions of the photons at a plane at the isocenter, and (2) creating a virtual point source from which photons are generated to yield the derived spatial spectral and fluence distribution at isocenter of an imaging system. The spatial photon distribution is determined by in‐air relative dose measurements along the transverse (x) and radial (y) directions. The spectrum is characterized using transverse axis half‐value layer measurements and the nominal peak potential (kVp). This source modeling approach is used to characterize a Varian® on‐board‐imager (OBI®) for four default cone‐beam CT beam qualities: beams using a half bowtie filter (HBT) with 110 and 125 kVp, and a full bowtie filter (FBT) with 100 and 125 kVp. The source model and characterization method was validated by comparing dose computed by the authors’ inhouse software (kVDoseCalc) to relative dose measurements in a homogeneous and a heterogeneous block phantom comprised of tissue, bone, and lung‐equivalent materials.

Results:

The characterized beam qualities and spatial photon distributions are comparable to reported values in the literature. Agreement between computed and measured percent depth‐dose curves is ⩽2% in the homogeneous block phantom and ⩽2.5% in the heterogeneous block phantom. Transverse axis profiles taken at depths of 2 and 6 cm in the homogeneous block phantom show an agreement within 4%. All transverse axis dose profiles in water, in bone, and lung‐equivalent materials for beams using a HBT, have an agreement within 5%. Measured profiles of FBT beams in bone and lung‐equivalent materials were higher than their computed counterparts resulting in an agreement within 2.5%, 5%, and 8% within solid water, bone, and lung, respectively.

Conclusions:

The proposed virtual point source model and characterization method can be used to compute absorbed dose in both the homogeneous and heterogeneous block phantoms within of 2%–8% of measured values, depending on the phantom and the beam quality. The authors’ results also provide experimental validation for their kV dose computation software, kVDoseCalc.
Deriving adaptive MRF coefficients from previous normal‐dose CT scan for low‐dose image reconstruction via penalized weighted least‐squares minimization
Authors: Zhang Hao , Han Hao , Wang Jing , Ma Jianhua , Liu Yan , Moore William , Liang Zhengrong
Published: March 2014

Purpose:

Repeated computed tomography (CT) scans are required for some clinical applications such as image‐guided interventions. To optimize radiation dose utility, a normal‐dose scan is often first performed to set up reference, followed by a series of low‐dose scans for intervention. One common strategy to achieve the low‐dose scan is to lower the x‐ray tube current and exposure time (mAs) or tube voltage (kVp) setting in the scanning protocol, but the resulted image quality by the conventional filtered back‐projection (FBP) method may be severely degraded due to the excessive noise. Penalized weighted least‐squares (PWLS) image reconstruction has shown the potential to significantly improve the image quality from low‐mAs acquisitions, where the penalty plays an important role. In this work, the authorsˈ explore an adaptive Markov random field (MRF)‐based penalty term by utilizing previous normal‐dose scan to improve the subsequent low‐dose scans image reconstruction.

Methods:

In this work, the authors employ the widely‐used quadratic‐form MRF as the penalty model and explore a novel idea of using the previous normal‐dose scan to obtain the MRF coefficients for adaptive reconstruction of the low‐dose images. In the coefficients determination, the authors further explore another novel idea of using the normal‐dose scan to obtain a scale map, which describes an optimal neighborhood for the coefficients determination such that a local uniform region has a small spread of frequency spectrum and, therefore, a small MRF window, andvice versa. The proposed penalty term is incorporated into the PWLS image reconstruction framework, and the low‐dose images are reconstructed via the PWLS minimization.

Results:

The presented adaptive MRF based PWLS algorithm was validated by physical phantom and patient data. The experimental results demonstrated that the presented algorithm is superior to the PWLS reconstruction using the conventional Gaussian MRF penalty or the edge‐preserving Huber penalty and the conventional FBP method, in terms of image noise reduction and edge/detail/contrast preservation.

Conclusions:

This study demonstrated the feasibility and efficacy of the proposed scheme in utilizing previous normal‐dose CT scan to improve the subsequent low‐dose scans.
Tumor detection in automated breast ultrasound images using quantitative tissue clustering
Authors: Moon Woo Kyung , Lo Chung‐Ming , Chen Rong‐Tai , Shen Yi‐Wei , Chang Jung Min , Huang Chiun‐Sheng , Chen Jeon‐Hor , Hsu Wei‐Wen , Chang Ruey‐Feng
Published: March 2014

Purpose:

A computer‐aided detection (CADe) system based on quantitative tissue clustering algorithm was proposed to identify potential tumors in automated breast ultrasound (ABUS) images.

Methods:

Our three‐dimensional (3D) ABUS images database included 148 biopsy‐verified lesions (size 0.4–7.9 cm; mean 1.76 cm). An ABUS volume was comprised of 229–282 slices of two‐dimensional (2D) images. For tumor detection, the fast 3D mean shift method was used to remove the speckle noise and the segment tissues with similar properties. The hypoechogenic regions, i.e., the tumor candidates, were extracted using fuzzy c‐means clustering. Seven features related to echogenicity and morphology were quantified and used to predict the likelihood of identifying a tumor and filtering out the false‐positive (FP) regions.

Results:

The sensitivity of the proposed CADe system achieved 89.19% (132/148) with 2.00 FPs per volume. For the volumes without lesion, the FP rate was 1.27. The sensitivity was 92.50% (74/80) for malignant tumors and 85.29% (58/68) for benign tumors.

Conclusions:

The proposed CADe system provides an automatic and quantitative procedure for tumor detection in ABUS images. Further studies are needed to reduce the FP rate of the CADe algorithm.
Computerized segmentation of pulmonary nodules depicted in CT examinations using freehand sketches
Authors: Qiang Yongqian , Wang Qiuping , Xu Guiping , Ma Hongxia , Deng Lei , Zhang Lei , Pu Jiantao , Guo Youmin
Published: March 2014

Purpose:

To aid a consistent segmentation of pulmonary nodules, the authors describe a novel computerized scheme that utilizes a freehand sketching technique and an improved break‐and‐repair strategy.

Methods:

This developed scheme consists of two primary parts. The first part is freehand sketch analysis, where the freehand sketching not only serves a natural way of specifying the location of a nodule, but also provides a mechanism for inferring adaptive information (e.g., the mass center, the density, and the size) in regard to the nodule. The second part is an improved break‐and‐repair strategy. The improvement avoids the time‐consuming ray‐triangle intersections using spherical bins and replaces the original global implicit surface reconstruction with a local implicit surface fitting and blending scheme. The performance of this scheme, including accuracy and consistence, was assessed using 50 CT examinations in the Lung Image Database Consortium (LIDC). For each of these examinations, a single nodule was selected under the aid of a publically available tool to assure these nodules were diverse in size, location, and density. Two radiologists were asked to use the developed tool to segment these nodules twice at different times (at least three months apart). A Hausdorff distance based method was used to assess the discrepancies (agreements) between the computerized results and the results by the four radiologists in the LIDC as well as the inter‐ and intrareader agreements in freehand sketching.

Results:

The maximum and mean discrepancies in boundary outlines between the computerized scheme and the radiologists were 2.73 ± 1.32 mm and 1.01 ± 0.47 mm, respectively. When the nodules were classified (binned) into different size ranges, the maximum errors ranged from 1.91 to 4.13 mm; but smaller nodules had larger percentage discrepancies in term of size. Under the aid of the developed scheme, the inter‐ and intrareader variability in averaged maximum discrepancy across all types of pulmonary nodules were consistently smaller than 0.15 ± 0.07 mm. The computational cost in time of segmenting a pulmonary nodule ranged from 0.4 to 2.3 s with an average of 1.1 s for a typical desktop computer.

Conclusions:

The experiments showed that this scheme could achieve a reasonable performance in nodule segmentation and demonstrated the merits of incorporating freehand sketching into pulmonary nodule segmentation.
Autoregressive model for high-resolution wavenumber estimation in a shallow water environment using a broadband source
Authors: Le Courtois Florent , Bonnel Julien
Published: March 2014

In a shallow water environment, wavenumbers can be estimated by computing time and spatial Fourier transforms of horizontal array measurements. The frequency-wavenumber representation allows wide band estimation but a sufficient number of hydrophones are required for accurate wavenumber resolution. This paper presents the application of an autoregressive (AR) model to compute the high resolution wavenumber spectrum. The smallest number of required sensors for the AR model is found using a stabilization diagram. The method is validated on simulated and experimental data. The wavenumbers are accurately estimated over a wide frequency band using fewer sensors than are needed for the spatial Fourier Transform.
Microbial Community Stratification Linked to Utilization of Carbohydrates and Phosphorus Limitation in a Boreal Peatland at Marcell Experimental Forest, Minnesota, USA
Authors: Lin Xueju , Tfaily Malak M. , Steinweg J. Megan , Chanton Patrick , Esson Kaitlin , Yang Zamin K. , Chanton Jeffrey P. , Cooper William , Schadt Christopher W. , Kostka Joel E.
Published: March 2014

This study investigated the abundance, distribution, and composition of microbial communities at the watershed scale in a boreal peatland within the Marcell Experimental Forest (MEF), Minnesota, USA. Through a close coupling of next-generation sequencing, biogeochemistry, and advanced analytical chemistry, a biogeochemical hot spot was revealed in the mesotelm (30- to 50-cm depth) as a pronounced shift in microbial community composition in parallel with elevated peat decomposition. The relative abundance of
Acidobacteria
and the
Syntrophobacteraceae
, including known hydrocarbon-utilizing genera, was positively correlated with carbohydrate and organic acid content, showing a maximum in the mesotelm. The abundance of
Archaea
(primarily crenarchaeal groups 1.1c and 1.3) increased with depth, reaching up to 60% of total small-subunit (SSU) rRNA gene sequences in the deep peat below the 75-cm depth. Stable isotope geochemistry and potential rates of methane production paralleled vertical changes in methanogen community composition to indicate a predominance of acetoclastic methanogenesis mediated by the
Methanosarcinales
in the mesotelm, while hydrogen-utilizing methanogens predominated in the deeper catotelm. RNA-derived pyrosequence libraries corroborated DNA sequence data to indicate that the above-mentioned microbial groups are metabolically active in the mid-depth zone. Fungi showed a maximum in rRNA gene abundance above the 30-cm depth, which comprised only an average of 0.1% of total bacterial and archaeal rRNA gene abundance, indicating prokaryotic dominance. Ratios of C to P enzyme activities approached 0.5 at the acrotelm and catotelm, indicating phosphorus limitation. In contrast, P limitation pressure appeared to be relieved in the mesotelm, likely due to P solubilization by microbial production of organic acids and C-P lyases. Based on path analysis and the modeling of community spatial turnover, we hypothesize that P limitation outweighs N limitation at MEF, and microbial communities are structured by the dominant shrub,
Chamaedaphne calyculata
, which may act as a carbon source for major consumers in the peatland.
Development of a Homologous Expression System for and Systematic Site-Directed Mutagenesis Analysis of Thurincin H, a Bacteriocin Produced by Bacillus thuringiensis SF361
Authors: Wang Gaoyan , Manns David C. , Churey John J. , Worobo Randy W.
Published: March 2014

Thurincin H is an antimicrobial peptide produced by
Bacillus thuringiensis
SF361. With a helical back bone, the 31 amino acids of thurincin H form a hairpin structure maintained by four pairs of very unique sulfur-to-α-carbon thioether bonds. The production of thurincin H depends on a putative gene cluster containing 10 open reading frames. The gene cluster includes three tandem structural genes (
thnA1
,
thnA2
, and
thnA3
) encoding three identical 40-amino-acid thurincin H prepeptides and seven other genes putatively responsible for prepeptide processing, regulation, modification, exportation, and self-immunity. A homologous thurincin H expression system was developed by transforming a thurincin H-deficient host with a novel expression vector, pGW133. The host, designated
B. thuringiensis
SF361 Δ
thnA1
Δ
thnA2
Δ
thnA3
, was constructed by deletion of the three tandem structural genes from the chromosome of the natural thurincin H producer. The thurincin H expression vector pGW133 was constructed by cloning the thurincin H native promoter,
thnA1
, and a Cry protein terminator into the
Escherichia coli
-
B. thuringiensis
shuttle vector pHT315. Thirty-three different pGW133 variants, each containing a different point mutation in the
thnA1
gene, were generated and separately transformed into
B. thuringiensis
SF361 Δ
thnA1
Δ
thnA2
Δ
thnA3
. Those site-directed mutants contained either a single radical or conservative amino acid substitution on the thioether linkage-forming positions or a radical substitution on all other nonalanine amino acids. The bacteriocin activities of
B. thuringiensis
SF361 Δ
thnA1
Δ
thnA2
Δ
thnA3
carrying different pGW133 variants against three different indicator strains were subsequently compared.
Directed Evolution of Unspecific Peroxygenase from Agrocybe aegerita
Authors: Molina-Espeja Patricia , Garcia-Ruiz Eva , Gonzalez-Perez David , Ullrich René , Hofrichter Martin , Alcalde Miguel
Published: March 2014

Unspecific peroxygenase (UPO) represents a new type of heme-thiolate enzyme with self-sufficient mono(per)oxygenase activity and many potential applications in organic synthesis. With a view to taking advantage of these properties, we subjected the
Agrocybe aegerita
UPO1-encoding gene to directed evolution in
Saccharomyces cerevisiae
. To promote functional expression, several different signal peptides were fused to the mature protein, and the resulting products were tested. Over 9,000 clones were screened using an
ad hoc
dual-colorimetric assay that assessed both peroxidative and oxygen transfer activities. After 5 generations of directed evolution combined with hybrid approaches, 9 mutations were introduced that resulted in a 3,250-fold total activity improvement with no alteration in protein stability. A breakdown between secretion and catalytic activity was performed by replacing the native signal peptide of the original parental type with that of the evolved mutant; the evolved leader increased functional expression 27-fold, whereas an 18-fold improvement in the
k
cat
/

K
m

value for oxygen transfer activity was obtained. The evolved UPO1 was active and highly stable in the presence of organic cosolvents. Mutations in the hydrophobic core of the signal peptide contributed to enhance functional expression up to 8 mg/liter, while catalytic efficiencies for peroxidative and oxygen transfer reactions were increased by several mutations in the vicinity of the heme access channel. Overall, the directed-evolution platform described is a valuable point of departure for the development of customized UPOs with improved features and for the study of structure-function relationships.
Raman Spectroscopy of Microbial Pigments
Authors: Jehlička Jan , Edwards Howell G. M. , Oren Aharon
Published: March 2014

Raman spectroscopy is a rapid nondestructive technique providing spectroscopic and structural information on both organic and inorganic molecular compounds. Extensive applications for the method in the characterization of pigments have been found. Due to the high sensitivity of Raman spectroscopy for the detection of chlorophylls, carotenoids, scytonemin, and a range of other pigments found in the microbial world, it is an excellent technique to monitor the presence of such pigments, both in pure cultures and in environmental samples. Miniaturized portable handheld instruments are available; these instruments can be used to detect pigments in microbiological samples of different types and origins under field conditions.
Spontaneously Induced Prophages in Lactobacillus gasseri Contribute to Horizontal Gene Transfer
Authors: Baugher J. L. , Durmaz E. , Klaenhammer T. R.
Published: March 2014

Lactobacillus gasseri
is an endogenous species of the human gastrointestinal tract and vagina. With recent advances in microbial taxonomy, phylogenetics, and genomics,
L. gasseri
is recognized as an important commensal and is increasingly being used in probiotic formulations.
L. gasseri
strain ADH is lysogenic and harbors two inducible prophages. In this study, prophage ϕadh was found to spontaneously induce in broth cultures to populations of ∼10
7
PFU/ml by stationary phase. The ϕadh prophage-cured ADH derivative NCK102 was found to harbor a new, second inducible phage, vB_Lga_jlb1 (jlb1). Phage jlb1 was sequenced and found to be highly similar to the closely related phage LgaI, which resides as two tandem prophages in the neotype strain
L. gasseri
ATCC 33323. The common occurrence of multiple prophages in
L. gasseri
genomes, their propensity for spontaneous induction, and the high degree of homology among phages within multiple species of
Lactobacillus
suggest that temperate bacteriophages likely contribute to horizontal gene transfer (HGT) in commensal lactobacilli. In this study, the host ranges of phages ϕadh and jlb1 were determined against 16
L. gasseri
strains. The transduction range and the rate of spontaneous transduction were investigated in coculture experiments to ascertain the degree to which prophages can promote HGT among a variety of commensal and probiotic lactobacilli. Both ϕadh and jlb1 particles were confirmed to mediate plasmid transfer. As many as ∼10
3
spontaneous transductants/ml were obtained. HGT by transducing phages of commensal lactobacilli may have a significant impact on the evolution of bacteria within the human microbiota.
Genes of the
N
-Methylglutamate Pathway Are Essential for Growth of Methylobacterium extorquens DM4 with Monomethylamine
Authors: Gruffaz Christelle , Muller Emilie E. L. , Louhichi-Jelail Yousra , Nelli Yella R. , Guichard Gilles , Bringel Françoise
Published: March 2014

Monomethylamine (MMA, CH
3
NH
2
) can be used as a carbon and nitrogen source by many methylotrophic bacteria.
Methylobacterium extorquens
DM4 lacks the MMA dehydrogenase encoded by
mau
genes, which in
M. extorquens
AM1 is essential for growth on MMA. Identification and characterization of minitransposon mutants with an MMA-dependent phenotype showed that strain DM4 grows with MMA as the sole source of carbon, energy, and nitrogen by the
N
-methylglutamate (NMG) pathway. Independent mutations were found in a chromosomal region containing the genes
gmaS
,
mgsABC
, and
mgdABCD
for the three enzymes of the pathway, γ-glutamylmethylamide (GMA) synthetase, NMG synthase, and NMG dehydrogenase, respectively. Reverse transcription-PCR confirmed the operonic structure of the two divergent gene clusters
mgsABC-gmaS
and
mgdABCD
and their induction during growth with MMA. The genes
mgdABCD
and
mgsABC
were found to be essential for utilization of MMA as a carbon and nitrogen source. The gene
gmaS
was essential for MMA utilization as a carbon source, but residual growth of mutant DM4
gmaS
growing with succinate and MMA as a nitrogen source was observed. Plasmid copies of
gmaS
and the
gmaS
homolog METDI4690, which encodes a protein 39% identical to GMA synthetase, fully restored the ability of mutants DM4
gmaS
and DM4
gmaS
Δmetdi4690 to use MMA as a carbon and nitrogen source. Similarly, chemically synthesized GMA, the product of GMA synthetase, could be used as a nitrogen source for growth in the wild-type strain, as well as in DM4
gmaS
and DM4
gmaS
Δmetdi4690 mutants. The NADH:ubiquinone oxidoreductase respiratory complex component NuoG was also found to be essential for growth with MMA as a carbon source.