The molecular basis of antigenic drift was determined for the hemagglutinin (HA) of human influenza A/H3N2 virus. From 1968 to 2003, antigenic change was caused mainly by single amino acid ...substitutions, which occurred at only seven positions in HA immediately adjacent to the receptor binding site. Most of these substitutions were involved in antigenic change more than once. Equivalent positions were responsible for the recent antigenic changes of influenza B and A/H1N1 viruses. Substitution of a single amino acid at one of these positions substantially changed the virus-specific antibody response in infected ferrets. These findings have potentially far-reaching consequences for understanding the evolutionary mechanisms that govern influenza viruses.
Titanium dioxide white pigment consists of particles of various sizes, from which a fraction is in the nano range (<100 nm). It is applied in food as additive E 171 as well as in other products, such ...as food supplements and toothpaste. Here, we assessed whether a human health risk can be expected from oral ingestion of these titanium dioxide nanoparticles (TiO
2
NPs), based on currently available information. Human health risks were assessed using two different approaches: Approach 1, based on intake, i.e. external doses, and Approach 2, based on internal organ concentrations using a kinetic model in order to account for accumulation over time (the preferred approach). Results showed that with Approach 1, a human health risk is not expected for effects in liver and spleen, but a human health risk cannot be excluded for effects on the ovaries. When based on organ concentrations by including the toxicokinetics of TiO
2
NPs (Approach 2), a potential risk for liver, ovaries and testes is found. This difference between the two approaches shows the importance of including toxicokinetic information. The currently estimated risk can be influenced by factors such as absorption, form of TiO
2
, particle fraction, particle size and physico-chemical properties in relation to toxicity, among others. Analysis of actual particle concentrations in human organs, as well as organ concentrations and effects in liver and the reproductive system after chronic exposure to well-characterized TiO
2
(NPs) in animals are recommended to refine this assessment.
The electrocatalytic conversion of furanic compounds, i.e. mainly furfural and 5-hydroxymethylfurfural, has recently emerged as a potentially scalable technology for both oxidation and hydrogenation ...processes because of its highly valuable products. However, its practical application in industry is currently limited by low catalytic activity and product selectivity. Thus, a better understanding of the catalytic reactions as well as a strategy for the catalyst design can bring solutions for a complete and selective conversion into desired products. In this perspective, we review the status and challenges of electrocatalytic oxidation and hydrogenation of furanic compounds, including thermodynamics, voltammetric studies, and bulk electrolysis with important reaction parameters (i.e., catalyst, electrolyte, temperature, etc.) and reaction mechanisms. In addition, we introduce methods of energy-efficient electrocatalytic furanic synthesis by combining yields of anodic and cathodic reactions in a paired reactor or a reactor powered by a renewable energy source (i.e., solar energy). Current challenges and future opportunities are also discussed, aiming at industrial applications.
Quantification of plasma free metanephrine (MN) and normetanephrine (NMN) is considered to be the most accurate test for the clinical chemical diagnosis of pheochromocytoma and follow-up of ...pheochromocytoma patients. Current methods involve laborious, time-consuming, offline sample preparation, coupled with relatively nonspecific detection. Our aim was to develop a rapid, sensitive, and highly selective automated method for plasma free MNs in the nanomole per liter range.
We used online solid-phase extraction coupled with HPLC-tandem mass spectrometric detection (XLC-MS/MS). Fifty microliters plasma equivalent was prepurified by automated online solid-phase extraction, using weak cation exchange cartridges. Chromatographic separation of the analytes and deuterated analogs was achieved by hydrophilic interaction chromatography. Mass spectrometric detection was performed in the multiple reaction monitoring mode using a quadrupole tandem mass spectrometer in positive electrospray ionization mode.
Total run-time including sample cleanup was 8 min. Intra- and interassay analytical variation (CV) varied from 2.0% to 4.7% and 1.6% to 13.5%, respectively, whereas biological intra- and interday variation ranged from 9.4% to 45.0% and 8.4% to 23.2%. Linearity in the 0 to 20 nmol/L calibration range was excellent (R(2) > 0.99). For all compounds, recoveries ranged from 74.5% to 99.6%, and detection limits were <0.10 nmol/L. Reference intervals for 120 healthy adults were 0.07 to 0.33 nmol/L (MN), 0.23 to 1.07 nmol/L (NMN), and <0.17 nmol/L (3-methoxytyramine).
This automated high-throughput XLC-MS/MS method for the measurement of plasma free MNs is precise and linear, with short analysis time and low variable costs. The method is attractive for routine diagnosis of pheochromocytoma because of its high analytical sensitivity, the analytical power of MS/MS, and the high diagnostic accuracy of free MNs.
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•Humins are original unique macromolecules, sub-products during polysaccharide conversion.•Furfuryl alcohol/humins resins with good viscosity, stability and curing behaviour were ...prepared.•New thermosetting materials suitable for applications in a.o. building products were produced.
Nowadays biobased building materials are used in various fields and for a wide range of applications such as polymers, fillers, coatings, adhesives, impregnation materials or high performance composites. This work focuses on humins, a biomacromolecular by-product of a HydroxyMethylFurfural/FuranDiCarboxylic Acid biorefinery. Humins are obtained by acidic treatment of polysaccharides and show very interesting potential as a reactive, semi-ductile thermoset matrix to impregnate cellulosic fibres. Therefore, humins have the essential characteristics to develop a new class of thermoset materials and composites, offering excellent possibilities to increase the renewable carbon content of the final products and improve its properties. A proper characterization of the neat humins in terms of solubility, flow behaviour and thermal resistance is essential in order to find the optimal parameters of processing humins solutions as well as co-reactive mixtures for impregnations or to prepare composites. In addition the study further indicates that humins enhance the modulus and the tensile strength of pure polyfurfurylalcohol resins. It was also shown that there is a difference in behaviour when sulfuric acid or maleic anhydride is used as initiator. The most optimal initiator will depend on application and preferred processing conditions. These encouraging results assure an important future for humins as economic green matrix for the production of composites and wood impregnation.
Familial clustering of adult idiopathic interstitial pneumonias (IIP) suggests that genetic factors might play an important role in disease development. Mutations in the gene encoding surfactant ...protein C (SFTPC) have been found in children and families with idiopathic pneumonias, whereas cocarriage of a mutation in ATP-binding cassette subfamily A member 3 (ABCA3) was postulated to have a disease-modifying effect.
To investigate the contribution of SFTPC mutations to adult familial pulmonary fibrosis (FPF) and the disease-modifying effect of mutations in ABCA3 within their families.
Twenty-two unrelated patients with FPF (10%) were identified within our single-center cohort of 229 patients with IIP. SFTPC was sequenced in 20 patients with FPF and 20 patients with sporadic IIP. In patients with an SFTPC mutation, sequencing of ABCA3 was performed. Discovered variants were typed in more than 100 control subjects and 121 additional patients with sporadic IIP.
In 5/20 unrelated patients with FPF (25%; confidence interval, 10-49) a mutation in SFTPC was detected: M71V, IVS4+2, and three times I73T. No mutations were detected in the sporadic or control cohort. Patients with SFTPC mutations presented with a histopathological pattern of usual interstitial pneumonia and nodular septa thickening and multiple lung cysts in combination with ground glass or diffuse lung involvement on chest high-resolution computed tomography. Two variants in ABCA3 were found in adult patients with FPF but not in affected children.
Mutations in SFTPC are a frequent cause of FPF in adult patients in our cohort. Nonclassifiable radiological patterns with cystic changes and histopathological patterns of usual interstitial pneumonia are characteristics of adult SFTPC mutation carriers.
Antigenic and genetic analysis of the hemagglutinin of ~13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and ...Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.
Objectives
To determine the effect of computer-aided-detection (CAD) software for automated breast ultrasound (ABUS) on reading time (RT) and performance in screening for breast cancer.
Material and ...methods
Unilateral ABUS examinations of 120 women with dense breasts were randomly selected from a multi-institutional archive of cases including 30 malignant (20/30 mammography-occult), 30 benign, and 60 normal cases with histopathological verification or ≥ 2 years of negative follow-up. Eight radiologists read once with (CAD-ABUS) and once without CAD (ABUS) with > 8 weeks between reading sessions. Readers provided a BI-RADS score and a level of suspiciousness (0-100). RT, sensitivity, specificity, PPV and area under the curve (AUC) were compared.
Results
Average RT was significantly shorter using CAD-ABUS (133.4 s/case, 95% CI 129.2-137.6) compared with ABUS (158.3 s/case, 95% CI 153.0-163.3) (
p
< 0.001). Sensitivity was 0.84 for CAD-ABUS (95% CI 0.79-0.89) and ABUS (95% CI 0.78-0.88) (
p
= 0.90). Three out of eight readers showed significantly higher specificity using CAD. Pooled specificity (0.71, 95% CI 0.68-0.75 vs. 0.67, 95% CI 0.64-0.70,
p
= 0.08) and PPV (0.50, 95% CI 0.45-0.55 vs. 0.44, 95% CI 0.39-0.49,
p
= 0.07) were higher in CAD-ABUS vs. ABUS, respectively, albeit not significantly. Pooled AUC for CAD-ABUS was comparable with ABUS (0.82 vs. 0.83,
p
= 0.53, respectively).
Conclusion
CAD software for ABUS may decrease the time needed to screen for breast cancer without compromising the screening performance of radiologists.
Key Points
•
ABUS with CAD software may speed up reading time without compromising radiologists’ accuracy.
• CAD software for ABUS might prevent non-detection of malignant breast lesions by radiologists.
• Radiologists reading ABUS with CAD software might improve their specificity without losing sensitivity.
The antigenic evolution of influenza A (H3N2) virus was quantified and visualized from its introduction into humans in 1968 to 2003. Although there was remarkable correspondence between antigenic and ...genetic evolution, significant differences were observed: Antigenic evolution was more punctuated than genetic evolution, and genetic change sometimes had a disproportionately large antigenic effect. The method readily allows monitoring of antigenic differences among vaccine and circulating strains and thus estimation of the effects of vaccination. Further, this approach offers a route to predicting the relative success of emerging strains, which could be achieved by quantifying the combined effects of population level immune escape and viral fitness on strain evolution.
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