bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural characterization of polypropylene/poly(lactic acid) bicomponent meltblown
Authors: Rungiah Selven , Ruamsuk Renukarn , Vroman Philippe , Takarada Wataru , Appert‐Collin Jean‐Christophe , Kikutani Takeshi
Published: December 2016

The bicomponent meltblown process offers to associate two polymers in the same fiber generating fibrous media with new properties. In this study, we associate polypropylene (PP) and poly(lactic acid) (PLA), from renewable sources, polymers. The influence of primary air flow rate and the structural properties of the PP/PLA bicomponent meltblown are compared to PP and PLA monocomponent meltblown. The structural properties include fiber morphology and diameter, packing density, permeability, thermal shrinkage and crystallization. The results relate that the PP/PLA bicomponent meltblown fiber diameters are thinner than those of PLA monocomponent. Moreover, it has higher resistance to thermal shrinkage compared to PP monocomponent meltblown. The packing density and permeability are not affected by the association of PP and PLA due to low crimp effect. Two different filament formations of PP/PLA bicomponent meltblown at low and high primary air flow rate have also been observed. Lastly, this study illustrates that PP and PLA association is viable, showing the production of PP/PLA bicomponent microfiber and limited thermal shrinkage at high temperature. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44540.
In vivo metabolite identification of acotiamide in rats using ultra‐performance liquid chromatography–quadrupole/time‐of‐flight mass spectrometry
Authors: Patel Prinesh N. , Kalariya Pradipbhai D. , Thummar Mohit , Gananadhamu S. , Srinivas R.
Published: December 2016

Acotiamide hydrochloride (ACT) is a drug used for the treatment of functional dyspepsia. Understanding which metabolites are likely to be formed in vivo is essential for interpreting pharmacology, pharmacokinetic and toxicology data. The metabolism of ACT has been investigated using a specific and sensitive liquid chromatography positive ion electrospray ionization high‐resolution tandem mass spectrometry method. In vivo samples including rat plasma, urine and feces were collected separately after dosing healthy Sprague–Dawley rats at a dose of 20 mg kg −1 ACT at different time points up to 24 h. The metabolites were enriched by optimized sample preparation involving protein precipitation using acetonitrile followed by solid‐phase extraction. The mass defect filter technique was used for better detection of both predicted and unexpected drug metabolites with the majority of interference ions removed. The structural elucidation of the metabolites was performed by comparing their [M + H]+ ions and their product ions with those of the parent drug. As a result, a total of seven hitherto unknown metabolites were characterized from the biosamples. The only phase I metabolite detected was N‐despropyl acotiamide, whereas six phase II glucuronide conjugate metabolites were identified.
Schistosomicidal Effects of the Essential Oils of Citrus limonia and Citrus reticulata Against Schistosoma mansoni
Authors: Martins Moara H. G. , Fracarolli Letícia , Vieira Tatiana M. , Dias Herbert J. , Cruz Michele G. , Deus Cássia C. H. , Nicolella Heloiza D. , Stefani Ricardo , Rodrigues Vanderlei , Tavares Denise C. , Magalhães Lizandra G. , Crotti Antônio E. M.
Published: December 2016

We report the in vitro schistosomicidal effects of the essential oil obtained from Citrus limonia leaves (CL‐EO) and C. reticulata fruit peels (CR‐EO), cultivated in Brazil, against Schistosoma mansoni worms. Limonene (29.9%), β‐pinene (12.0%), sabinene (9.0%), citronellal (9.0%), and citronellol (5.8%) are the major constituents of CL‐EO; limonene (26.5%), γ‐terpinene (17.2%), linalool (11.1%), octanal (8.0%), myrcene (6.2%), and capraldehyde (3.9%) predominate in CR‐EO. CL‐EO displayed moderate lethal concentration 50% (LC50) of 81.7 and 38.9 μg/ml against male and female worms at 24 and 72 h, respectively. At concentrations of 25 and 100 μg/ml, CL‐EO separated between 50 and 75% of the coupled worm pairs during the evaluated period. CR‐EO presented moderate LC50 of 81.7 μg/ml against male and female worms at 24 and 72 h. However, this oil separated coupled worm pairs more effectively than CL‐EO and displayed lower cytotoxicity to GM07492‐A cells (IC50 = 987.7 ± 88.9 μg/ml) as compared to CL‐EO (IC50 = 187.8 ± 2.9 μg/ml). The enantiomers (+)‐(R)‐limonene and (−)‐(S)‐limonene did not affect S. mansoni adult worm pairs significantly. Taken together, these data indicate that CL‐EO and CR‐EO exhibit moderate in vitro schistosomicidal activity against adult S. mansoni worms.
Five New C19‐Diterpenoid Alkaloids from Delphinium tianshanicum W.T.Wang
Authors: Zhang Ji‐Fa , Shan Lian‐Hai , Gao Feng , Huang Shuai , Zhou Xian‐Li
Published: December 2016

Five new diterpenoid alkaloids, tianshanitines A‐E (1 – 5), along with ten known compounds (6 – 15), were isolated from the EtOH extracts of the whole plant of Delphinium tianshanicum W.T.Wang. Their structures were determined based on extensive spectroscopic analyses, including 1D‐ and 2D‐NMR, HR‐ESI‐MS, and the structure of tianshanitine C (3) was confirmed by X‐ray diffraction analysis. Tianshanitine A (1) is the first example of natural diterpenoid alkaloid containing a benzoyl group at C(1) position. Tianshanitine B (2) is a rare natural diterpenoid alkaloid bearing a OH group at C(16) position. Compounds 1 – 5, 6, 8, 10, 12 and 14 were evaluated for cytotoxicity against HCT116, MCF‐7 and HepG2 human cancer cell lines.
New Furanone Derivatives and Alkaloids from the Co‐Culture of Marine‐Derived Fungi Aspergillus sclerotiorum and Penicillium citrinum
Authors: Bao Jie , Wang Jie , Zhang Xiao‐Yong , Nong Xu‐Hua , Qi Shu‐Hua
Published: December 2016

Six new compounds including two furanone derivatives sclerotiorumins A and B (1 and 2), one novel oxadiazin derivative sclerotiorumin C (3), one pyrrole derivative 1‐(4‐benzyl‐1H‐pyrrol‐3‐yl)ethanone (4), and two complexes of neoaspergillic acid aluminiumneohydroxyaspergillin (5) and ferrineohydroxyaspergillin (6) were isolated from the co‐culture of marine‐derived fungi Aspergillus sclerotiorum and Penicillium citrinum. Compound 3 was the first natural 1,2,4‐oxadiazin‐6‐one. Compound 5 showed significant and selective cytotoxicity against human histiocytic lymphoma U937 cell line (IC50 = 4.2 μm) and strong toxicity towards brine shrimp (LC50 = 6.1 μm), and oppositely increased the growth and biofilm formation of Staphylococcus aureus.
Variability of Pinus halepensis Mill. Essential Oils and Their Antioxidant Activities Depending on the Stage of Growth During Vegetative Cycle
Authors: Djerrad Zineb , Djouahri Abderrahmane , Kadik Leila
Published: December 2016

The impact of growth stages during vegetative cycle (B0 – B5) on chemical composition and antioxidant activities of Pinus halepensis Mill. needles essential oils was investigated for the first time. GC and GC/MS analyses pointed to a quantitative variability of components; terpene hydrocarbons derivatives, represented by α‐pinene (8.5 – 12.9%), myrcene (17.5 – 21.6%), p‐cymene (7.9 – 11.9%) and (Z)‐β‐caryophyllene (17.3 – 21.2%) as major components, decreased from 88.9% at B0 growth stage to 66.9% at B5 growth stage, whereas oxygenated derivatives, represented by caryophyllene oxide (5.4 – 12.6%) and terpinen‐4‐ol (0.4 – 3.3%) as major components, increased from 7% at B0 growth stage to 28.4% at B5 growth stage. Furthermore, our findings showed that essential oil of P. halepensis needles collected at B5 growth stage possess higher antioxidant activities by four different testing systems than those collected at B0 – B4 growth stages. This highlighted variability led to conclude that we should select essential oils to be investigated carefully depending on growth stage, in order to have the highest effectiveness of essential oil in terms of biological activities for human health purposes.
An Unconventional Acid‐Labile Nucleobase Protection Concept for Guanosine Phosphoramidites in RNA Solid‐Phase Synthesis
Authors: Jud Lukas , Micura Ronald
Published: December 2016

We present an innovative O6‐tert‐butyl/N2‐tert‐butyloxycarbonyl protection concept for guanosine (G) phosphoramidites. This concept is advantageous for 2′‐modified G building blocks because of very efficient synthetic access when compared with existing routes that usually employ O6‐(4‐nitrophenyl)ethyl/N2‐acyl protection or that start from 2‐aminoadenosine involving enzymatic transformation into guanosine later on in the synthetic path. The new phosphoramidites are fully compatible with 2′‐O‐tBDMS or TOM phosphoramidites in standard RNA solid‐phase synthesis and deprotection, and provide excellent quality of tailored RNAs for the growing range of applications in RNA biophysics, biochemistry, and biology.
13C NMR Spectroscopy of N‐Heterocyclic Carbenes Can Selectively Probe σ Donation in Gold(I) Complexes
Authors: Marchione Demian , Izquierdo Maria A. , Bistoni Giovanni , Havenith Remco W. A. , Macchioni Alceo , Zuccaccia Daniele , Tarantelli Francesco , Belpassi Leonardo
Published: December 2016

The Dewar–Chatt–Duncanson (DCD) model provides a successful theoretical framework to describe the nature of the chemical bond in transition‐metal compounds and is especially useful in structural chemistry and catalysis. However, how to actually measure its constituents (substrate‐to‐metal donation and metal‐to‐substrate back‐donation) is yet uncertain. Recently, we demonstrated that the DCD components can be neatly disentangled and the π back‐donation component put in strict correlation with some experimental observables. In the present work we make a further crucial step forward, showing that, in a large set of charged and neutral N‐heterocyclic carbene complexes of gold(I), a specific component of the NMR chemical shift tensor of the carbenic carbon provides a selective measure of the σ donation. This work opens the possibility of 1) to characterize unambiguously the electronic structure of a metal fragment (LAu(I)n+/0 in this case) by actually measuring its σ‐withdrawing ability, 2) to quickly establish a comparative trend for the ligand trans effect, and 3) to achieve a more rigorous control of the ligand electronic effect, which is a key aspect for the design of new catalysts and metal complexes.
Sodium co‐limits and catalyzes macronutrients in a prairie food web
Authors: Kaspari Michael , Roeder Karl A. , Benson Brittany , Weiser Michael D. , Sanders Nathan J.
Published: December 2016

Nitrogen and phosphorus frequently limit terrestrial plant production, but have a mixed record in regulating the abundance of terrestrial invertebrates. We contrasted four ways that Na could interact with anNPfertilizer to shape the plants and invertebrates of an inland prairie. We appliedNPand Na to m2plots in a factorial design. Aboveground invertebrate abundance was independently co‐limited by NaCl andNP, but with +NPplots supporting more individuals. We suggest the disparity arises becauseNPenhanced plant height by 35% (1 SD) over controls, providing both food and habitat, whereas NaCl provides only food. Belowground invertebrates showed evidence of serial co‐limitation, where NaCl additions alone were ineffectual, but catalyzed access toNP. This suggests the increased belowground food availability inNPplots increased Na demand. Na andNPsupply rates vary with climate, land use, and with inputs like urine. The co‐limitation and catalysis of N and P by Na thus has the potential for predicting patterns of abundance and diversity across spatial scales.
Variations in the response of the dune coast of northern France to major storms as a function of available beach sediment volume
Authors: Crapoulet Adrien , Héquette Arnaud , Marin Denis , Levoy Franck , Bretel Patrice
Published: December 2016

A series of airborne topographic LiDAR data were obtained from May 2008 to January 2014 over two coastal sites of northern France (Bay of Wissant and east of Dunkirk). These data were used with wind and tide gauge measurements to assess the impacts of storms on beaches and coastal dunes, and particularly of the series of major storms that hit western Europe during the fall and early winter of 2013. Our results show a high variability in shoreline response from one site to the other, but also within each coastal site. Coastal dune erosion and shoreline retreat occurred at both sites, particularly on the coast of the Bay of Wissant where shoreline retreat up to about 40 m was measured. However, stability or even shoreline advance were also observed despite the occurrence of an extreme water level with a return period >100 years during the storm Xaver in early December 2013. Comparison of shoreline change with variations of coastal dune and upper beach volumes revealed only weak relationships. Our results nevertheless showed that shoreline behavior seems to strongly depend on the initial sediment volume on the upper beach before the occurrence of the storms. According to our measurements, an upper beach volume of about 30 m3 m−1 between the dune toe and the mean high water level is sufficient at these sites to protect the coastal dunes from storm waves associated with high water levels with return periods >10 years. The identification of such thresholds in terms of upper beach width or sediment volume may represent valuable information for improving the management of shoreline change by providing an estimate of the minimum quantity of sand on the upper beach necessary to ensure shoreline stability in this region. Copyright © 2016 John Wiley & Sons, Ltd.
Adaptive smoothing based on Gaussian processes regression increases the sensitivity and specificity of fMRI data
Authors: Strappini Francesca , Gilboa Elad , Pitzalis Sabrina , Kay Kendrick , McAvoy Mark , Nehorai Arye , Snyder Abraham Z.
Published: December 2016

Temporal and spatial filtering of fMRI data is often used to improve statistical power. However, conventional methods, such as smoothing with fixed‐width Gaussian filters, remove fine‐scale structure in the data, necessitating a tradeoff between sensitivity and specificity. Specifically, smoothing may increase sensitivity (reduce noise and increase statistical power) but at the cost loss of specificity in that fine‐scale structure in neural activity patterns is lost. Here, we propose an alternative smoothing method based on Gaussian processes (GP) regression for single subjects fMRI experiments. This method adapts the level of smoothing on a voxel by voxel basis according to the characteristics of the local neural activity patterns. GP‐based fMRI analysis has been heretofore impractical owing to computational demands. Here, we demonstrate a new implementation of GP that makes it possible to handle the massive data dimensionality of the typical fMRI experiment. We demonstrate how GP can be used as a drop‐in replacement to conventional preprocessing steps for temporal and spatial smoothing in a standard fMRI pipeline. We present simulated and experimental results that show the increased sensitivity and specificity compared to conventional smoothing strategies. Hum Brain Mapp 38:1438–1459, 2017. © 2016 Wiley Periodicals, Inc.
Lifetime alcohol intake is associated with an increased risk of KRAS+ and BRAF‐/KRAS‐ but not BRAF+ colorectal cancer
Authors: Jayasekara Harindra , MacInnis Robert J. , Williamson Elizabeth J. , Hodge Allison M. , Clendenning Mark , Rosty Christophe , Walters Rhiannon , Room Robin , Southey Melissa C. , Jenkins Mark A. , Milne Roger L. , Hopper John L. , Giles Graham G. , Buchanan Daniel D. , English Dallas R.
Published: December 2016

Ethanol in alcoholic beverages is a causative agent for colorectal cancer. Colorectal cancer is a biologically heterogeneous disease, and molecular subtypes defined by the presence of somatic mutations in BRAF and KRAS are known to exist. We examined associations between lifetime alcohol intake and molecular and anatomic subtypes of colorectal cancer. We calculated usual alcohol intake for 10‐year periods from age 20 using recalled frequency and quantity of beverage‐specific consumption for 38,149 participants aged 40–69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between lifetime alcohol intake and colorectal cancer risk. Heterogeneity in the HRs across subtypes of colorectal cancer was assessed. A positive dose‐dependent association between lifetime alcohol intake and overall colorectal cancer risk (mean follow‐up = 14.6 years; n = 596 colon and n = 326 rectal cancer) was observed (HR = 1.08, 95% CI: 1.04–1.12 per 10 g/day increment). The risk was greater for rectal than colon cancer (phomogeneity = 0.02). Alcohol intake was associated with increased risks of KRAS+ (HR = 1.07, 95% CI: 1.00–1.15) and BRAF−/KRAS− (HR = 1.05, 95% CI: 1.00–1.11) but not BRAF+ tumors (HR = 0.89, 95% CI: 0.78–1.01; phomogeneity = 0.01). Alcohol intake is associated with an increased risk of KRAS+ and BRAF−/KRAS‐ tumors originating via specific molecular pathways including the traditional adenoma‐carcinoma pathway but not with BRAF+ tumors originating via the serrated pathway. Therefore, limiting alcohol intake from a young age might reduce colorectal cancer originating via the traditional adenoma‐carcinoma pathway.
Non‐internalizing antibody–drug conjugates display potent anti‐cancer activity upon proteolytic release of monomethyl auristatin E in the subendothelial extracellular matrix
Authors: Gébleux Rémy , Stringhini Marco , Casanova Ruben , Soltermann Alex , Neri Dario
Published: December 2016

Antibody–drug conjugates (ADCs) represent a promising class of biopharmaceuticals with the potential to localize at the tumor site and improve the therapeutic index of cytotoxic drugs. While it is generally believed that ADCs need to be internalized into tumor cells in order to display optimal therapeutic activity, it has recently been shown that non‐internalizing antibodies can efficiently liberate disulfide‐linked drugs at the extracellular tumor site, leading to potent anti‐cancer activity in preclinical animal models. Here, we show that engineered variants of the F16 antibody, specific to a splice isoform of tenascin‐C, selectively localize to the subendothelial tumor extracellular matrix in three mouse models of human cancer (U87, A431, MDA‐MB‐231). A site‐specific coupling of F16 in IgG format with a monomethyl auristatin E (MMAE) derivative, featuring a valine‐citrulline dipeptide linker equipped with a self‐immolative spacer, yielded an ADC product, which cured tumor‐bearing mice at a dose of 7 mg/Kg. The observation of an efficient extracellular proteolytic cleavage of the valine‐citrulline linker was surprising, as it has generally been assumed that this peptidic structure would be selectively cleaved by cathepsin B in intracellular compartments. The products described in this article may be useful for the treatment of human malignancies, as their cognate antigen is strongly expressed in the majority of human solid tumors, lymphomas and aggressive leukemias, while being virtually undetectable in most normal adult tissues.
Foscan and foslip based photodynamic therapy in osteosarcoma in vitro and in intratibial mouse models
Authors: Meier Daniela , Botter Sander M. , Campanile Carmen , Robl Bernhard , Gräfe Susanna , Pellegrini Giovanni , Born Walter , Fuchs Bruno
Published: December 2016

Current osteosarcoma therapies cause severe treatment‐related side effects and chemoresistance, and have low success rates. Consequently, alternative treatment options are urgently needed. Photodynamic therapy (PDT) is a minimally invasive, local therapy with proven clinical efficacy for a variety of tumor types. PDT is cytotoxic, provokes anti‐vascular effects and stimulates tumor cell targeting mechanisms of the immune system and, consequently, has potential as a novel therapy for osteosarcoma patients. This study investigated the uptake and the dark‐ and phototoxicity and cytotoxic mechanisms of the photosensitizer (PS) 5,10,15,20‐tetrakis(meta‐hydroxyphenyl) chlorine (mTHPC, Foscan) and a liposomal mTHPC formulation (Foslip) in the human 143B and a mouse K7M2‐derived osteosaroma cell line (K7M2L2) in vitro. Second, the tumor‐ and metastasis‐suppressive efficacies of mTHPC formulations based PDT and associated mechanisms in intratibial, metastasizing osteosarcoma mouse models (143B/SCID and syngeneic K7M2L2/BALB/c) were studied. The uptake of Foscan and Foslip in vitro was time‐ and dose‐dependent and resulted in mTHPC and light dose‐dependent phototoxicity associated with apoptosis. In vivo, the uptake of both i.v. administered mTHPC formulations was higher in tumor than in healthy control tissue. PDT caused significant (Foscan p < 0.05, Foslip p < 0.001) tumor growth inhibition in both models. A significant (Foscan p < 0.001, Foslip p < 0.001) immune system‐dependent suppression of lung metastasis was only observed in the K7M2L2/BALB/c model and was associated with a marked infiltration of T‐lymphocytes at the primary tumor site. In conclusion, mTHPC‐based PDT is effective in clinically relevant experimental osteosarcoma and suppresses lung metastasis in immunocompetent mice with beneficial effects of the liposomal mTHPC formulation Foslip.
ATF for cell culture harvest clarification: mechanistic modelling and comparison with TFF
Authors: Hadpe Sandeep Ramesh , Sharma Abhishek Kumar , Mohite Vipin Vilas , Rathore Anurag S
Published: December 2016

BACKGROUND

Extracellular expression of proteins in mammalian cell culture systems requires clarification in order to separate the cell mass from soluble expressed protein. This task is typically accomplished by membrane based separations. This paper explores the use of alternating tangential flow (ATF) filtration for clarification.

RESULTS

The superiority of ATF over the conventional tangential flow filtration (TFF) has been demonstrated with respect to the required sizing of the filter and both processes have been modeled. Modeling of TFF is based on assumptions of constant conditions of pressure, concentration of foulant, or flux. Modeling of ATF involved simultaneous variations in all three parameters and hence the traditional models that describe fouling of membranes under constant pressure filtration were appropriately modified to incorporate these variations. The resulting models are amenable to ‘exponent analysis’ and allow identification of the mechanism of ATF fouling among pore blocking, intermediate pore blocking, pore constriction, and cake formation. Complete pore blocking has been identified as the dominant mechanism for the system at hand involving clarification of mammalian cell culture harvests using ATF as well as TFF.

CONCLUSIONS

ATF has been implemented and successfully demonstrated to be superior to TFF for mammalian cell culture clarification. The mechanism of fouling with ATF as well as TFF has been identified successfully. The modeling approach proposed here can be applied to a variety of industrial systems to determine the mode of fouling and to mitigate it. Also, sizing predictions based on mechanistic modeling can be useful for process optimization. © 2016 Society of Chemical Industry
ZNF208 polymorphisms associated with ischemic stroke in a southern Chinese Han population
Authors: Yu Jianzhong , Zhou Feng , Luo Dong , Wang Nianzhen , Zhang Chong , Jin Tianbo , Liang Xiongfei , Yu Dan
Published: December 2016

Background

Ischemic stroke is one of the most common diseases with a high burden of neurological deficits, disability and death. Zinc finger protein 208 (ZNF208) was found to be involved in coronary heart disease, although little information is available about its association with ischemic stroke. We performed the present case–control study to clarify the association between single‐nucleotide polymorphisms (SNPs) within ZNF208 and the risk of ischemic stroke in a southern Chinese Han population.

Methods

A total of 799 subjects (400 cases and 399 healthy controls) were enrolled in the present study. Five SNPs within ZNF208 gene were selected and genotyped using Sequenom MassARRY technology (Sequenom, Inc., San Diego, CA, USA). Data management and statistical analyses were conducted using Sequenom Typer, version 4.0, and a chi‐squared test, as well as unconditional logistic regression.

Results

Statistical results showed that three variants were associated with the risk of ischemic stroke under allele models (rs2188971, rs2188972, rs8103163 and rs7248488). The variant rs2188972 was also associated with the risk of ischemic stroke in a recessive model after adjustment for age and sex. Haplotype analysis suggested that a significant difference existed between the Ars2188972 Trs2188971 Ars8103163 Ars7248488 haplotype and the risk of ischemic stroke, although this disappeared after adjustment for sex and age.

Conclusions

The results obtained in the present study indicate a potential association between ZNF208 variants and the risk of ischemic risk in a southern Chinese Han population.
Molecular diversity in irregular or refugee immigrant patients with HBV‐genotype‐E infection living in the metropolitan area of Naples
Authors: Sagnelli Caterina , Ciccozzi Massimo , Coppola Nicola , Minichini Carmine , Lo Presti Alessandra , Starace Mario , Alessio Loredana , Macera Margherita , Cella Eleonora , Gualdieri Luciano , Caprio Nunzio , Pasquale Giuseppe , Sagnelli Evangelista
Published: December 2016

In a recent testing in the metropolitan area of Naples, Italy, on 945 irregular immigrants or refugees, 87 HBsAg chronic carriers were identified, 53 of whom were infected by HBV‐genotype E. The aim of the present study was to identify the genetic diversity of HBV‐genotype E in these 53 immigrants. The 53 immigrant patients with HBV‐genotype‐E infection were born in Africa, central or eastern Asia, eastern Europe or Latin America. These patients had been seen for a clinical consultation at one of the four first‐level units from January 2012 to 2013. The first dataset contained 53 HBV‐S gene isolates plus 128 genotype/subgenotype specific reference sequences downloaded from the National Center for Biotechnology Information. The second dataset, comprising the 53 HBV‐S gene isolates, previously classified as HBV‐genotype E, was used to perform the time‐scaled phylogeny reconstruction using a Bayesian approach. Phylogenetic analysis showed that all 53 HBV‐S isolates belonged to HBV‐genotype E. Bayes factor analysis showed that the relaxed clock exponential growth model fitted the data significantly better than the other models. The time‐scaled Bayesian phylogenetic tree of the second dataset showed that the root of the tree dated back to the year 1990 (95% HPD:1984–2000). Four statistically supported clusters were identified. Cluster A dated back to 2012 (95% HPD:1997–2012); cluster B dated back to 2008 (95% HPD:2001–2015); cluster C to 2006 (95% HPD:1999–2013); cluster D to 2004 (95% HPD:1998–2011). This study disclosed the genetic evolution and phylogenesis in a group of HBV‐genotype‐E‐infected immigrants. J. Med. Virol. 89:1015–1024, 2017. © 2016 Wiley Periodicals, Inc.
Testing the Modified Sediment Delivery Model (MOSEDD) at SPA2 Experimental Basin, Sicily (Italy)
Authors: Di Stefano Costanza , Ferro Vito
Published: December 2016

A new version of a spatially distributed sediment delivery model taking into account the hillslope sediment transport efficiency, named MOSEDD, is presented. This model gives estimates of basin sediment yield at event scale, which are more reliable than those obtained by the original SEDD. For SPA2 basin discretized into morphological units, four different calculation schemes of MOSEDD, including the original SEDD version, were applied. All parameterization schemes of the model were calibrated using 15 events measured at the outlet of the experimental basin in the period February 2005–February 2010. The model calibration was used to determine a relationship between the coefficient βe of the model and the erosivity factor. For the model validation, other six measured events, collected in the period March 2010–February 2014, were used. At event scale, the comparison between measured sediment yield values and calculated ones showed that the three calculation schemes of MOSEDD using a rainfall–runoff erosivity factor (MODB, MODC and MODD) have the best performance in estimating sediment yield with respect to the original version of SEDD. The analysis was also developed at annual scale, for the period 2005–2014, and a relationship between the annual value of the coefficient, βa, of the model and the corresponding erosivity factor was established. This last analysis showed that the sediment delivery distributed approach has also a good predictive ability at annual scale. Copyright © 2016 John Wiley & Sons, Ltd.
On the potential for RF heating in MRI to affect metabolic rates and 18FDG signal in PET/MR: simulations of long‐duration, maximum normal mode heating
Authors: Carluccio Giuseppe , Ding Yu‐Shin , Logan Jean , Collins Christopher M.
Published: December 2016

Purpose

To examine the possibility that MR‐induced RF power deposition (SAR) and the resulting effects on temperature‐dependent metabolic rates or perfusion rates might affect observed 18FDG signal in PET/MR.

Methods

Using numerical simulations of the SAR, consequent temperature increase, effect on rates of metabolism or perfusion, and [18FDG] throughout the body, we simulated the potential effect of maximum‐allowable whole‐body SAR for the entire duration of an hour‐long PET/MR scan on observed PET signal for two different 18FDG injection times: one hour before onset of imaging and concurrent with the beginning of imaging. This was all repeated three times with the head, the heart, and the abdomen (kidneys) at the center of the RF coil.

Results

Qualitatively, little effect of MR‐induced heating is observed on simulated PET images. Maximum relative increases in PET signal (26% and 31% increase, respectively, for the uptake models based on metabolism and the perfusion) occur in regions of low baseline metabolic rate (also associated with low perfusion and, thus, greater potential temperature increase due to high local SAR), such that PET signal in these areas remains comparatively low. Maximum relative increases in regions of high metabolic rate (and also high perfusion: heart, thyroid, brain, etc.) are affected mostly by the relatively small increase in core body temperature and thus are not affected greatly (10% maximum increase).

Conclusions

Even for worst‐case heating, little effect of MR‐induced heating is expected on 18FDG PET images during PET/MR for many clinically relevant applications. For quantitative, dynamic MR/PET studies requiring high SAR for extended periods, it is hoped that methods like those introduced here can help account for such potential effects in design of a given study, including selection of reference locations that should not experience notable increase in temperature.
Direct diffusion tensor estimation using a model‐based method with spatial and parametric constraints
Authors: Zhu Yanjie , Peng Xi , Wu Yin , Wu Ed X. , Ying Leslie , Liu Xin , Zheng Hairong , Liang Dong
Published: December 2016

Purpose

To develop a new model‐based method with spatial and parametric constraints (MB‐SPC) aimed at accelerating diffusion tensor imaging (DTI) by directly estimating the diffusion tensor from highly undersampled k‐space data.

Methods

The MB‐SPC method effectively incorporates the prior information on the joint sparsity of different diffusion‐weighted images using an L1–L2 norm and the smoothness of the diffusion tensor using a total variation seminorm. The undersampled k‐space datasets were obtained from fully sampled DTI datasets of a simulated phantom and an ex‐vivo experimental rat heart with acceleration factors ranging from 2 to 4. The diffusion tensor was directly reconstructed by solving a minimization problem with a nonlinear conjugate gradient descent algorithm. The reconstruction performance was quantitatively assessed using the normalized root mean square error (nRMSE) of the DTI indices.

Results

The MB‐SPC method achieves acceptable DTI measures at an acceleration factor up to 4. Experimental results demonstrate that the proposed method can estimate the diffusion tensor more accurately than most existing methods operating at higher net acceleration factors.

Conclusion

The proposed method can significantly reduce artifact, particularly at higher acceleration factors or lower SNRs. This method can easily be adapted to MR relaxometry parameter mapping and is thus useful in the characterization of biological tissue such as nerves, muscle, and heart tissue.
Converting computed tomography images into photon interaction coefficients by using stoichiometric calibration and parametric fit models
Authors: Shih Cheng‐Ting , Wu Jay
Published: December 2016

Purpose

X ray and γ‐ray are widely applied in radiology, radiotherapy, and nuclear medicine. Linear attenuation coefficients and linear energy absorption coefficients are essential for dose calculation and image correction. In this study, a method that entails combining the stoichiometric calibration and parametric physical models was developed to convert computed tomography (CT) images into the linear attenuation coefficients and linear energy absorption coefficients.

Methods

A calibration scan was performed using standard tissue‐equivalent materials to obtain the characteristics of the x‐ray energy spectrum. Subsequently, relationships between CT numbers and tissue parameters were established using standard soft tissue and bone tissue data adopted from the literature. The linear attenuation coefficient and linear energy absorption coefficient were calculated using the parametric fit model.

Results

The results showed a linear relationship between CT numbers and tissue parameters. The tissue‐equivalent materials differed from real human tissues, leading to considerable errors in estimation of mass attenuation coefficients when the photon energy was lower than 50 keV. Mass attenuation coefficients and mass energy transfer coefficients of five tissues were calculated and validated using clinical CT images. The error was less than ± 5% and ± 8%, compared with the values of the International Commission on Radiation Units (ICRU) 46 report.

Conclusions

The probability of photon interaction with tissues and physical characteristics of tissues can be accurately evaluated by using the proposed method and applied in various clinical applications.
Examining the influence of humidity on reference ionization chamber performance
Authors: McEwen Malcolm R. , Taank Jaswinder
Published: December 2016

Purpose

International dosimetry protocols require measurements made with a vented ionization chamber to be corrected for the influence of air density by using the standard temperature‐pressure correction factor. The effect of humidity, on the other hand, is generally ignored with the provision that the relative humidity (RH) is within certain limits (typically 20% to 80%). However, there is little experimental data in the published literature as to the true effect of humidity on modern reference‐class ionization chambers. This investigation used two different radiation beams – a Co‐60 irradiator and an Sr‐90 check source – to examine the effect of humidity on several Farmer‐type ionization chambers.

Methods

An environmental cabinet controlled the humidity. For the Co‐60 beam, the irradiation was external, whereas for the Sr‐90 measurements, the source itself was placed within the cabinet. Extensive measurements were carried out to ensure that the experimental setup provided reproducible readings. Four chamber types were investigated: IBA FC65‐G, IBA FC65‐P, PTW 30013 and Exradin A19. The different wall materials provided potentially different mechanical responses (i.e., in terms of expansion/contraction) to the water content in the air. The relative humidity was varied between 8% and 98% and measurements were made with both increasing and decreasing humidity to investigate any possible hysteresis effects.

Results

Measurements in Co‐60 were consistent with the published data obtained with primary standard cavity chambers in ICRU Report 31 (i.e., a very small variation <0.1% for RH >10%). The measurements in the Sr‐90 field showed no dependence with the relative humidity, within the measurement uncertainties (0.05%, k = 1). Very good repeatability of the ionization current was obtained over successive wet/dry cycles, no hysteresis was observed, and there was no dependence on chamber type.

Conclusion

These results indicate that humidity has no significant effect on these particular types of ionization chambers, consistent with recommendations in current megavoltage dosimetry protocols.
A 2D silicon detector array for quality assurance in small field dosimetry: DUO
Authors: Shukaili Khalsa Al , Petasecca Marco , Newall Matthew , Espinoza Anthony , Perevertaylo Vladimir L. , Corde Stéphanie , Lerch Michael , Rosenfeld Anatoly B.
Published: December 2016

Purpose

Nowadays, there are many different applications that use small fields in radiotherapy treatments. The dosimetry of small radiation fields is not trivial due to the problems associated with lateral disequilibrium and source occlusion and requires reliable quality assurance (QA). Ideally such a QA tool should provide high spatial resolution, minimal beam perturbation and real time fast measurements. Many different types of silicon diode arrays are used for QA in radiotherapy; however, their application in small filed dosimetry is limited, in part, due to a lack of spatial resolution. The Center of Medical Radiation Physics (CMRP) has developed a new generation of a monolithic silicon diode array detector that will be useful for small field dosimetry in SRS/SRT. The objective of this study is to characterize a monolithic silicon diode array designed for dosimetry QA in SRS/SRT named DUO that is arranged as two orthogonal 1D arrays with 0.2 mm pitch.

Methods

DUO is two orthogonal 1D silicon detector arrays in a monolithic crystal. Each orthogonal array contains 253 small pixels with size 0.04 × 0.8 mm2 and three central pixels are with a size of 0.18 × 0.18 mm2 each. The detector pitch is 0.2 mm and total active area is 52 × 52 mm2. The response of the DUO silicon detector was characterized in terms of dose per pulse, percentage depth dose, and spatial resolution in a radiation field incorporating high gradients. Beam profile of small fields and output factors measured on a Varian 2100EX LINAC in a 6 MV radiation fields of square dimensions and sized from 0.5 × 0.5 cm2 to 5 × 5 cm2. The DUO response was compared under the same conditions with EBT3 films and an ionization chamber.

Results

The DUO detector shows a dose per pulse dependence of 5% for a range of dose rates from 2.7 × 10−4 to 1.2 × 10−4 Gy/pulse and 23% when the rate is further reduced to 2.8 × 10−5 Gy/pulse. The percentage depth dose measured to 25 cm depth in solid water phantom beyond the surface and for a field size of 10 × 10 cm2 agrees with that measured using a Markus IC within 1.5%. The beam profiles in both X and Y orthogonal directions showed a good match with EBT3 film, where the FWHM agreed within 1% and penumbra widths within 0.5 mm. The effect of an air gap above the DUO detector has also been studied. The output factor for field sizes ranging from 0.5 × 0.5 cm2 to 5 × 5 cm2 measured by the DUO detector with a 0.5 mm air gap above silicon surface agrees with EBT3 film and MOSkin detectors within 1.8%.

Conclusions

The CMRP's monolithic silicon detector array, DUO, is suitable for SRS/SRT dosimetry and QA because of its very high spatial resolution (0.2 mm) and real time operation.
Experimental investigation on spontaneous counter‐current imbibition in water‐wet natural reservoir sandstone core using MRI
Authors: Zhao Yuechao , Song Yongchen
Published: December 2016

Counter‐current imbibition is a process whereby a wetting phase spontaneously imbibes into a porous media, displacing the non‐wetting phase. This process is considered an important oil recovery mechanism during water flooding in fractured oil reservoirs. In this study, the dynamic process of counter‐current imbibition for a natural reservoir sandstone core with an all‐face‐open boundary condition was monitored using magnetic resonance imaging (MRI). A series of images and relaxation time T1 spectra were acquired. The movement of water spontaneously entering the core sample while oil escapes, the spatial distribution of oil and water, and the in situ saturation change of oil and water in porous media can be accurately detected using MRI. MRI assists the direct evaluation of the basic mechanisms of imbibitions. Experimental results suggest the remaining oil was trapped in some large pores because of the capillary pressure, and the oil recovery in some large‐pore regions is lower than that in some small‐pore regions at the end of imbibition. Experimental findings show a close agreement between conventional material balance and oil recovery determined from MRI. The in situ oil recovery data agree well with the empirical models. The observations from MRI images could provide test cases to enable the development of mathematical models and to facilitate the evaluation of the proposed imbibition mechanisms. Copyright © 2016 John Wiley & Sons, Ltd.
Autocalibrating motion‐corrected wave‐encoding for highly accelerated free‐breathing abdominal MRI
Authors: Chen Feiyu , Zhang Tao , Cheng Joseph Y. , Shi Xinwei , Pauly John M. , Vasanawala Shreyas S.
Published: December 2016

Purpose

To develop a motion‐robust wave‐encoding technique for highly accelerated free‐breathing abdominal MRI.

Methods

A comprehensive 3D wave‐encoding‐based method was developed to enable fast free‐breathing abdominal imaging: (a) auto‐calibration for wave‐encoding was designed to avoid extra scan for coil sensitivity measurement; (b) intrinsic butterfly navigators were used to track respiratory motion; (c) variable‐density sampling was included to enable compressed sensing; (d) golden‐angle radial‐Cartesian hybrid view‐ordering was incorporated to improve motion robustness; and (e) localized rigid motion correction was combined with parallel imaging compressed sensing reconstruction to reconstruct the highly accelerated wave‐encoded datasets. The proposed method was tested on six subjects and image quality was compared with standard accelerated Cartesian acquisition both with and without respiratory triggering. Inverse gradient entropy and normalized gradient squared metrics were calculated, testing whether image quality was improved using paired t‐tests.

Results

For respiratory‐triggered scans, wave‐encoding significantly reduced residual aliasing and blurring compared with standard Cartesian acquisition (metrics suggesting P < 0.05). For non‐respiratory‐triggered scans, the proposed method yielded significantly better motion correction compared with standard motion‐corrected Cartesian acquisition (metrics suggesting P < 0.01).

Conclusion

The proposed methods can reduce motion artifacts and improve overall image quality of highly accelerated free‐breathing abdominal MRI. Magn Reson Med 78:1757–1766, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Prophylactic window therapy with the clinical poly(ADP‐ribose) polymerase inhibitor olaparib delays BRCA1‐deficient mammary tumour formation in mice
Authors: van de Ven Marieke , van der Burg Eline , van der Gulden Hanneke , Klarenbeek Sjoerd , Bouwman Peter , Jonkers Jos
Published: December 2016

Women with heterozygous germline mutations in the BRCA1 tumour suppressor gene are strongly predisposed to developing early‐onset breast cancer through loss of the remaining wild‐type BRCA1 allele and inactivation of TP53. Although tumour prevention strategies in BRCA1‐mutation carriers are still limited to prophylactic surgery, several therapeutic strategies have been developed to target the DNA repair defects (also known as ‘BRCAness’) of BRCA1‐deficient tumours. In particular, DNA‐damaging agents such as platinum drugs and poly(ADP‐ribose) polymerase (PARP) inhibitors show strong activity against BRCA1‐mutated tumours. However, it is unclear whether drugs that target BRCAness can also be used to prevent tumour formation in BRCA1‐mutation carriers, especially as loss of wild‐type BRCA1 may not be the first event in BRCA1‐associated tumourigenesis. We performed prophylactic treatments in a genetically engineered mouse model in which de novo development of BRCA1‐deficient mammary tumours is induced by stochastic loss of BRCA1 and p53. We found that prophylactic window therapy with nimustine, cisplatin or olaparib reduced the amount and size of mammary gland lesions, and significantly increased the median tumour latency. Similar results were obtained with intermittent prophylactic treatment with olaparib. Importantly, prophylactic window therapy with nimustine and cisplatin resulted in an increased fraction of BRCA1‐proficient mammary tumours, suggesting selective survival and malignant transformation of BRCA1‐proficient lesions upon prophylactic treatment with DNA‐damaging agents. Prophylactic therapy with olaparib significantly prolonged mammary tumour‐free survival without any significant increase in the fraction of BRCA1‐proficient tumours, warranting the evaluation of this PARP inhibitor in prophylactic trials in BRCA1‐mutation carriers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
New additions to the ClusPro server motivated by CAPRI
Authors: Vajda Sandor , Yueh Christine , Beglov Dmitri , Bohnuud Tanggis , Mottarella Scott E. , Xia Bing , Hall David R. , Kozakov Dima
Published: December 2016

The heavily used protein–protein docking server ClusPro performs three computational steps as follows: (1) rigid body docking, (2) RMSD based clustering of the 1000 lowest energy structures, and (3) the removal of steric clashes by energy minimization. In response to challenges encountered in recent CAPRI targets, we added three new options to ClusPro. These are (1) accounting for small angle X‐ray scattering data in docking; (2) considering pairwise interaction data as restraints; and (3) enabling discrimination between biological and crystallographic dimers. In addition, we have developed an extremely fast docking algorithm based on 5D rotational manifold FFT, and an algorithm for docking flexible peptides that include known sequence motifs. We feel that these developments will further improve the utility of ClusPro. However, CAPRI emphasized several shortcomings of the current server, including the problem of selecting the right energy parameters among the five options provided, and the problem of selecting the best models among the 10 generated for each parameter set. In addition, results convinced us that further development is needed for docking homology models. Finally, we discuss the difficulties we have encountered when attempting to develop a refinement algorithm that would be computationally efficient enough for inclusion in a heavily used server. Proteins 2017; 85:435–444. © 2016 Wiley Periodicals, Inc.