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  • Wiley-Blackwell  (474,673)
  • American Institute of Physics (AIP)  (154,287)
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  • 1
    Publication Date: 2018-01-03
    Description: ABSTRACT The CO 2 solubility data in the ionic liquid (IL) 1-allyl-3-methylimidazolium bis(trifluoromethyl sulfonyl)imide, methanol (MeOH), and their mixture with different combinations at temperatures of (313.2, 333.2, and 353.2 K) and pressures up to 6.50 MPa were measured experimentally. New group binary interaction parameters of the predictive UNIFAC-Lei model, which has been continually advanced by our group, were introduced by correlating the experimental data of this work and the literature. The consistency between experimental data and predicted results proves the reliability of UNIFAC-Lei model for CO 2 -IL-organic solvent systems. The newly obtained parameters were incorporated into the UNIFAC property model of Aspen Plus software to optimize a conceptual process developed for the purification of a CO 2 -containing gas stream. The simulation results indicate that the use of IL either mixed with MeOH or purely considerably lowers the process power consumption, and improves the process performance in terms of CO 2 capture rate and solvent loss. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 2
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    Wiley-Blackwell
    Publication Date: 2018-01-03
    Print ISSN: 0248-4900
    Electronic ISSN: 1768-322X
    Topics: Biology
    Published by Wiley-Blackwell
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  • 3
    Publication Date: 2018-01-03
    Description: Vibrational circular dichroism (VCD) has become a standard method for determination of absolute stereochemistry, particularly now that reliable commercial instrumentation has become available. These instruments use a now well-documented Fourier transform infrared-based approach to measure VCD that has virtually displaced initial dispersive infrared-based designs. Nonetheless, many papers have appeared reporting dispersive VCD data, especially for biopolymers. Instrumentation designed with these original methods, particularly after more recent updates optimizing performance in selected spectral regions, has been shown still to have advantages for specific applications. This article presents a mini-review of dispersive VCD instrument designs and includes sample spectra obtained for various biopolymer (particularly peptide) samples. Complementary reviews of Fourier transform-VCD designs are broadly available.
    Print ISSN: 0899-0042
    Electronic ISSN: 1520-636X
    Topics: Chemistry and Pharmacology
    Published by Wiley-Blackwell
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  • 4
    Publication Date: 2018-01-03
    Description: Severe heart pathology upon virus infection is closely associated with the immunological equipment of the host. Since there is no specific treatment available, current research focuses on identifying new drug targets to positively modulate predisposing immune factors. Utilizing a murine model with high susceptibility to coxsackievirus B3-induced myocarditis, this study describes ONX 0914—an immunoproteasome-specific inhibitor—as highly protective during severe heart disease. Represented by reduced heart infiltration of monocytes/macrophages and diminished organ damage, ONX 0914 treatment reversed fulminant pathology. Virus-induced immune response features like overwhelming pro-inflammatory cytokine and chemokine production as well as a progressive loss of lymphocytes all being reminiscent of a sepsis-like disease course were prevented by ONX 0914. Although the viral burden was only minimally affected in highly susceptible mice, resulting maintenance of immune homeostasis improved the cardiac output, and saved animals from severe illness as well as high mortality. Altogether, this could make ONX 0914 a potent drug for the treatment of severe virus-mediated inflammation of the heart and might rank immunoproteasome inhibitors among drugs for preventing pathogen-induced immunopathology. Resembling disease course in patients pre-disposed for severe pathogen-induced cardiac pathology, A/J mice exhibit high susceptibility for virus-induced adverse immune response activation. Systemic application of the LMP7-specific immunoproteasome inhibitor ONX 0914 inversed this hereditary predisposition.
    Print ISSN: 1757-4676
    Electronic ISSN: 1757-4684
    Topics: Medicine
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  • 5
    Publication Date: 2018-01-03
    Description: Imbalanced T-helper (TH)1/Th2 response contributes significantly to asthma pathogenesis. Our study indicated that HMGB1 play an important role in the release of Th2-associated cytokines of asthma. However, the specific mechanism about HMGB1-induced imbalanced TH1/Th2 response is not known. In vivo, an OVA-induced asthma mouse model was set up and mice treated with anti-HMGB1 IgG. The mice treated with the anti-HMGB1 IgG ameliorated airway hyper-reactivity, disruption of Th1/Th2 balance and the upregulation of GRP75 induced by OVA. In vitro, the exposure of normal human bronchial epithelial cells to HMGB1 resulted in the upregulation of GRP75, proinflammatory cytokine production, enhanced ER–Mitochondrial Ca 2+ transfer and enhancement of reactive oxygen species (ROS). While HMGB1-induced these changes were attenuated by GRP75 siRNA treatment. Sequentially, pretreatment with 2-APB, SKF960365 (SKF) and Ru360 which inhibit ER–Mitochondrial Ca 2+ transfer significantly lowered HMGB1-induced the generation of ROS and the release of Th2 cytokines in 16HBE cells. Meanwhile, N-acetylcysteine (NAC) significantly attenuated the HMGB1-mediated pro-inflammatory cytokines release. Therefore, these results indicate that GRP75-mediated ER–Mitochondrial Ca 2+ transfer may be an important contributor in imbalanced of Th1/Th2 balance of asthma. Moreover, HMGB1 specifically induces the release of Th2 cytokines through GRP75-mediated enhancement of ER–Mitochondrial Ca 2+ transfer and ROS increased. This article is protected by copyright. All rights reserved
    Electronic ISSN: 0091-7419
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 6
    Publication Date: 2018-01-03
    Description: Many clinical laboratories now sequence the tumors from advanced cancer patients to identify oncogenic drivers and guide targeted therapies and clinical trials. One limitation of tumor sequencing is that it cannot distinguish between tumor-specific somatic (acquired) mutations and patients’ germline (constitutional) variants. To definitively identify somatic variants, some clinical labs sequence both a normal sample from a patient alongside their tumor to subtract the germline variants from the somatic variants. Having a paired normal sample also allows for the identification of secondary germline mutations in cancer patients who may not meet the current clinical guidelines for genetic testing of cancer predisposition syndromes. Such simultaneous detection of somatic alterations and germline mutations during tumor-normal sequencing can guide therapeutic decision making for cancer patients and the identification and screening of at-risk family members. Here, we review the clinical workflow, advantages and disadvantages, and clinical utility of tumor-normal sequencing in management of cancer patients.
    Print ISSN: 0022-3417
    Electronic ISSN: 1096-9896
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 7
    Publication Date: 2018-01-04
    Description: The kinetic characteristics of microwave-assisted pyrolysis of biomass components were investigated in a self-designed microwave TGA using the KAS model and the master plot method. Compared with conventional pyrolysis, the initial decomposition temperatures of biomass components were reduced by 50-100°C and the fastest weight loss regions were shifted to lower temperatures. The average apparent activation energies of cellulose, hemicellulose and lignin were 47.82, 44.81 and 51.54 kJ/mol, respectively. Analysis with master plot method suggested the MAP of cellulose followed the 2-D diffusion reaction model, while hemicellulose and lignin could be interpreted by 3rd order-based and 3-D diffusion model. The change of dielectric properties was consistent with the weight loss behaviors of biomass components during the pyrolysis process. The increase of dielectric properties with temperature can lead to a thermal gradient and “hot spots” within biomass, which accelerated the pyrolysis process at low temperatures and reduced the apparent activation energy. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 8
    Publication Date: 2018-01-04
    Description: The challenging of this work is to present a thorough study of implementing heat transfer intensification in heat exchanger network (HEN) retrofitting, including all details of exchanger geometry, stream bypassing and splitting, temperature-variation of properties, LMTD and its correction, and pressure drops. This leads to very complex mixed integer nonlinear programming (MINLP) problems rarely reported before. By adopting the MILP-based iterative approach proposed in the earlier work (Pan et al. in 2013), temperature-variation of properties, LMTD and its correction are initialised to parameters at first, and the rest nonlinear terms are then linearized and expressed as first order Taylor series expansions. Finally, two iteration loops are executed to find optimal solutions. A small-scale motivating problem and an industrial scale problem are presented to demonstrate the validity and efficiency of the proposed methods. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 9
    Publication Date: 2018-01-04
    Description: Membranes assembled from two-dimensional (2D) layered materials have shown potential use in water purification. Recently, a 2D graphitic carbon nitride (g-C 3 N 4 ) nanosheets membrane exhibit considerable separation performance in water purification. In this study, to further improve this water separation performance, polyacrylic acid (PAA) was introduced to tune the nanochannels formed between the g-C 3 N 4 nanosheets. The fabricated g-C 3 N 4 -PAA hybrid membranes possessed higher water flux without sacrificing much rejection rate compared with that of the g-C 3 N 4 membrane; however noticeable fouling was observed upon addition of the PAA into the membrane composite structure. In addition, the effect of PAA on the morphology, surface hydrophilicity, separation performance, and antifouling properties of the g-C 3 N 4 membrane were examined in detail. Overall, incorporating PAA into the g-C 3 N 4 nanosheets membrane was an effective and convenient method to improve the water separation performance, which could promote the application of the 2D g-C 3 N 4 nanosheets membrane in practical ultrafiltration processes. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 10
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    Wiley-Blackwell
    Publication Date: 2018-01-04
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 11
    Publication Date: 2018-01-04
    Description: BACKGROUND Mitogen-activated protein kinase (MAPK) activation and mammalian target of rapamycin (mTOR)-dependent signaling are hallmarks of glioblastoma. In the current study, the authors conducted a phase 1/2 study of sorafenib (an inhibitor of Raf kinase and vascular endothelial growth factor receptor 2 [VEGFR-2]) and the mTOR inhibitor temsirolimus in patients with recurrent glioblastoma. METHODS Patients with recurrent glioblastoma who developed disease progression after surgery or radiotherapy plus temozolomide and with ≤2 prior chemotherapy regimens were eligible. The phase 1 endpoint was the maximum tolerated dose (MTD), using a cohorts-of-3 design. The 2-stage phase 2 study included separate arms for VEGF inhibitor (VEGFi)–naive patients and patients who progressed after prior VEGFi. RESULTS The MTD was sorafenib at a dose of 200 mg twice daily and temsirolimus at a dose of 20 mg weekly. In the first 41 evaluable patients who were treated at the phase 2 dose, there were 7 who were free of disease progression at 6 months (progression-free survival at 6 months [PFS6]) in the VEGFi-naive group (17.1%); this finding met the prestudy threshold of success. In the prior VEGFi group, only 4 of the first 41 evaluable patients treated at the phase 2 dose achieved PFS6 (9.8%), and this did not meet the prestudy threshold for success. The median PFS for the 2 groups was 2.6 months and 1.9 months, respectively. The median overall survival for the 2 groups was 6.3 months and 3.9 months, respectively. At least 1 adverse event of grade ≥3 was observed in 75.5% of the VEGFi-naive patients and in 73.9% of the prior VEGFi patients. CONCLUSIONS The limited activity of sorafenib and temsirolimus at the dose and schedule used in the current study was observed with considerable toxicity of grade ≥3. Significant dose reductions that were required in this treatment combination compared with tolerated single-agent doses may have contributed to the lack of efficacy. Cancer 2018 . © 2018 American Cancer Society .
    Print ISSN: 0008-543X
    Electronic ISSN: 1097-0142
    Topics: Biology , Medicine
    Published by Wiley-Blackwell on behalf of The American Cancer Society.
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  • 12
    Publication Date: 2018-01-04
    Description: BACKGROUND Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53 . Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3% of individuals with osteosarcoma harbor a mutation in TP53 . New data from next-generation sequencing have demonstrated that 3.8% of patients with osteosarcoma have a known pathogenic variant, and an additional 5.7% carry exonic variants of unknown significance in TP53 . METHODS Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data. RESULTS One hundred seventy-seven pediatric oncologists (22%) responded to the survey. Respondents were more likely to offer TP53 testing to a patient with a positive family history (77.4% vs 12.4%; P 〈 .0001). Significantly more providers responded that they would offer TP53 testing once they were provided with the new data (25.4% vs 12.4%; P = .0038). The proportion of providers who responded that they were unsure increased significantly when they were presented with the new data (25.4% vs 10.2%; P = .0002). Potential implications for other family members and the possibility that surveillance imaging would detect new malignancies at an earlier stage were important factors influencing a provider's decision to offer TP53 testing. CONCLUSIONS Recent data increase the proportion of providers willing to offer testing, and this suggests concern on the part of pediatric oncologists that variants of unknown significance may be disease-defining in rare cancers. Cancer 2018 . © 2018 American Cancer Society .
    Print ISSN: 0008-543X
    Electronic ISSN: 1097-0142
    Topics: Biology , Medicine
    Published by Wiley-Blackwell on behalf of The American Cancer Society.
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  • 13
    Publication Date: 2018-01-04
    Description: Purpose The purpose of this study was to investigate the hyperpolarized ketone body 13 C-acetoacetate (AcAc) and its conversion to 13 C-β-hydroxybutyrate (βOHB) in vivo, catalyzed by β-hydroxybutyrate dehydrogenase (BDH), as a novel direct marker of mitochondrial redox state. Methods [1,3- 13 C 2 ]AcAc was synthesized by hydrolysis of the ethyl ester, and hyperpolarized via dissolution DNP. Cold storage under basic conditions resulted in sufficient chemical stability for use in hyperpolarized (HP) MRI studies. Polarizations and relaxation times of HP [1,3- 13 C 2 ]AcAc were measured in a clinical 3T MRI scanner, and 8 rats were scanned by dynamic HP 13 C MR spectroscopy of a slab through the kidneys. Four rats were scanned after acute treatment with high dose metformin (125 mg/kg, intravenous), which is known to modulate mitochondrial redox via inhibition of mitochondrial complex I. An additional metformin-treated rat was scanned by abdominal 2D CSI (8 mm × 8 mm). Results Polarizations of 7 ± 1% and 7 ± 3%, and T 1 relaxation times of 58 ± 5 s and 52 ± 3 s, were attained at the C 1 and C 3 positions, respectively. Rapid conversion of HP AcAc to βOHB was detected in rat kidney in vivo, via the C 1 label. The product HP βOHB was resolved from closely resonating acetate. Conversion to βOHB was also detected via 2D CSI, in both kidney as well as liver regions. Metformin treatment resulted in a significant increase (40%, P  = 0.01) of conversion of HP AcAc to βOHB. Conclusion Rapid conversion of HP AcAc to βOHB was observed in rat kidney in vivo and is a promising new non-invasive marker of mitochondrial redox state. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
    Print ISSN: 0740-3194
    Electronic ISSN: 1522-2594
    Topics: Medicine
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  • 14
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    Wiley-Blackwell
    Publication Date: 2018-01-04
    Print ISSN: 0740-3194
    Electronic ISSN: 1522-2594
    Topics: Medicine
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  • 15
    Publication Date: 2018-01-04
    Description: We describe a synthetic approach to prepare new luminescent silica-based materials through the encapsulation of a neutral copper(I) complex inside the pores of mesoporous silica nanoparticles (MSN). Interestingly the compound is present, in the solid state, as two polymorphs, blue and yellow emissive, and in solution it shows a pale yellow color that is also mirrored by an emission in the yellow-orange region of the electromagnetic spectrum. The X-ray structures of single crystals have been obtained for both polymorphs. The complex encapsulation in MSN is achieved by its entrapment inside micelles followed by condensation of the silica source. Interestingly, the entrapment leads to the isolation of only one species. Indeed, the compound inside the MSN exhibits remarkable photophysical properties, showing an intense blue emission in solution and in the solid state. Powder X-ray diffraction of the hybrid materials proves that the complex entrapped in MSN is indeed the blue polymorph. The confinement provides not only a method to isolate only one form of the complex, but also a certain rigidity, more stability of the system by protection of the complex from undesirable oxidation, leading to a highly emissive material possessing a photoluminescence quantum yield of 65%. This article is protected by copyright. All rights reserved.
    Print ISSN: 0018-019X
    Electronic ISSN: 1522-2675
    Topics: Chemistry and Pharmacology
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  • 16
    Publication Date: 2018-01-04
    Description: Aims Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leukocyte antigen (HLA) and β2M serve as key molecules in tumor immunity, and their expression is frequently reduced in tumor cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumor cells from T-cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and β2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL. Methods & Results We analyzed a total of 123 biopsy samples from patients newly diagnosed with ATLL by using immunohistochemical analysis. Of the patients enrolled, 91 (74%) were positive for HLA (in cell membrane, 60 patients), 89 (72%) were positive for β2M (in cell membrane, 54 patients), and 48 (39%) were positive for both HLA and β2M in the cell membrane (HLA m+ β2M m+ ). No significant clinical differences other than prognosis were found between the HLA m+ β2M m+ group and the other groups. Immunophenotypical evaluation revealed significantly higher rates of CD30-positive lymphoma cells ( P = 0.003) and PD-L1–positive stromal cells in microenvironments (miPD-L1 high ) ( P = 0.011) of the HLA m+ β2M m+ group than in the other groups. The HLA m+ β2M m+ group had significantly better prognosis that the other groups ( P = 0.0096), and patients showing HLA m+ β2M m+ with miPD-L1 high had the most-favorable prognosis among all groups. Conclusions The membranous expression of HLA and β2M is likely to reflect the immune response and would be useful to predict prognosis before starting ATLL therapy. This article is protected by copyright. All rights reserved.
    Print ISSN: 0309-0167
    Electronic ISSN: 1365-2559
    Topics: Medicine
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  • 17
    Publication Date: 2018-01-04
    Description: Current treatment options for human stroke are limited mainly to the modestly effective infusion of tissue plasminogen activator (tPA), with additional improvement of functional independence and higher rates of angiographic revascularization observed after mechanical thrombectomy. However, new therapeutic strategies that address post-stroke immune-mediated inflammatory responses are urgently needed. Recent studies in experimental stroke have firmly implicated immune mechanisms in the propagation and partial resolution of CNS damage after the ischemic event. A new-found anti-inflammatory role for regulatory B cells (Breg) in autoimmune diseases sparked interest in these cells as potential immunomodulators in stroke. Subsequent studies identified IL-10 as a common regulatory cytokine among all five of the currently recognized Breg cell subsets, several of which can be found in the affected brain hemisphere after induction of experimental stroke in mice. Transfer of enriched Breg cell subpopulations into both B-cell depleted and wild-type mice confirmed their potent immunosuppressive activities in vivo, including recruitment and potentiation of regulatory T cells. Moreover, Breg cell therapy strongly reduced stroke volumes and treatment outcomes in ischemic mice even when administered 24 hours after induction of experimental stroke, a treatment window far exceeding that of tPA. These striking results suggest that transfer of enriched Breg cell populations could have therapeutic value in human stroke, although considerable clinical challenges remain. This article is protected by copyright. All rights reserved.
    Print ISSN: 0019-2805
    Electronic ISSN: 1365-2567
    Topics: Medicine
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  • 18
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    Wiley-Blackwell
    Publication Date: 2018-01-04
    Description: Dendritic cells (DC) are a class of bone marrow derived cells arising from lympho-myeloid haematopoiesis that form an essential interface between the innate sensing of pathogens and the activation of adaptive immunity. This task requires a wide range of mechanisms and responses, which are divided between three major DC subsets: plasmacytoid DC (pDC), myeloid/conventional DC1 (cDC1) and myeloid/conventional DC2 (cDC2). Each DC subset develops under the control of a specific repertoire of transcription factors involving differential levels of IRF8 and IRF4 in collaboration with PU.1, ID2, E2-2, ZEB2, KLF4, IKAROS and BATF3. DC haematopoiesis is conserved between mammalian species and distinct from monocyte development. Although monocytes can differentiate into DC, especially during inflammation, most quiescent tissues contain significant resident populations of DC lineage cells. An extended range of surface markers facilitates the identification of specific DC subsets although it remains difficult to dissociate cDC2 from monocyte-derived DC in some settings. Recent studies based on an increasing level of resolution of phenotype and gene expression have identified pre-DC in human blood and heterogeneity among cDC2. These advances facilitate the integration of mouse and human immunology, support efforts to unravel human DC function in vivo and continue to present new translational opportunities to medicine. This article is protected by copyright. All rights reserved.
    Print ISSN: 0019-2805
    Electronic ISSN: 1365-2567
    Topics: Medicine
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  • 19
    Publication Date: 2018-01-05
    Description: Shell damage and parasitic infections are frequent in gastropods, influencing key snail host life-history traits such as survival, growth, and reproduction. However, their interactions and potential effects on hosts and parasites have never been tested. Host–parasite interactions are particularly interesting in the context of the recently discovered division of labor in trematodes infecting marine snails. Some species have colonies consisting of two different castes present at varying ratios; reproductive members and nonreproductive soldiers specialized in defending the colony. We assessed snail host survival, growth, and shell regeneration in interaction with infections by two trematode species, Philophthalmu s sp. and Maritrema novaezealandense , following damage to the shell in the New Zealand mud snail Zeacumantus subcarinatus . We concomitantly assessed caste-ratio adjustment between nonreproductive soldiers and reproductive members in colonies of the trematode Philophthalmu s sp. in response to interspecific competition and shell damage to its snail host. Shell damage, but not parasitic infection, significantly increased snail mortality, likely due to secondary infections by pathogens. However, trematode infection and shell damage did not negatively affect shell regeneration or growth in Z. subcarinatus ; infected snails actually produced more new shell than their uninfected counterparts. Both interspecific competition and shell damage to the snail host induced caste-ratio adjustment in Philophthalmu s sp. colonies. The proportion of nonreproductive soldiers increased in response to interspecific competition and host shell damage, likely to defend the parasite colony and potentially the snail host against increasing threats. These results indicate that secondary infections by pathogens following shell damage to snails both significantly increased snail mortality and induced caste-ratio adjustments in parasites. This is the first evidence that parasites with a division of labor may be able to produce nonreproductive soldiers according to environmental factors other than interspecific competition with other parasites. We assessed snail host survival, growth, and shell regeneration in interaction with infections by two trematode species following damage to the shell. We concomitantly assessed caste-ratio adjustment between nonreproductive soldiers and reproductive members in colonies of the trematode Philophthalmus sp. in response to interspecific competition and shell damage to its snail host. Shell damage, but not parasitic infection, significantly increased snail mortality, likely due to secondary infections by pathogens. The proportion of nonreproductive soldiers increased in response to interspecific competition and host shell damage. This is the first evidence that parasites with a division of labor may be able to produce nonreproductive soldiers according to environmental factors other than interspecific competition with other parasites.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 20
    Publication Date: 2018-01-05
    Description: Double infections of Wolbachia and Spiroplasma are frequent in natural populations of Tetranychus truncatus , a polyphagous mite species that has been a dominant species in China since 2009. However, little is known about the causes and ecological importance of such coexistences. In this study, we established T. truncatus strains with different infection types and then inferred the impact of the two endosymbionts on host reproduction and fitness. Double infection induced cytoplasmic incompatibility, which was demonstrated by reduction in egg hatchability of incompatible crosses. However, doubly infected females produced more eggs relative to other strains. Wolbachia and Spiroplasma did not affect host survival, whereas doubly infected females and males developed faster than other strains. Such reproduction and fitness benefits provided by double infections may be associated with the lower densities of each symbiont, and the quantitative results also confirmed competition between Wolbachia and Spiroplasma in doubly infected females. These symbiont-conferred beneficial effects maintain stable prevalence of the symbionts and also help drive T. truncatus outbreaks in combination with other environmental factors. The symbiont-conferred beneficial effects on spider mite Tetranychus truncatus maintain stable prevalence of the symbionts and also help drive spider mite outbreaks in combination with other environmental factors.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 21
    Publication Date: 2018-01-05
    Description: In group-living species, individuals often have preferred affiliative social partners, with whom ties or bonds can confer advantages that correspond with greater fitness. For example, in adult female baboons and juvenile horses, individuals with stronger or more social ties experience greater survival. We used detailed behavioral and life history records to explore the relationship between tie quality and survival in a gregarious monkey ( Cercopithecus mitis stuhlmanni ), while controlling for dominance rank, group size, and life history strategy. We used Cox proportional hazards regressions to model the cumulative (multi-year) and current (single-year) relationships of social ties and the hazard of mortality in 83 wild adult females of known age, observed 2–8 years each (437 subject-years) in eight social groups. The strength of bonds with close partners was associated with increased mortality risk under certain conditions: Females that had strong bonds with close partners that were inconsistent over multiple years had a higher risk of mortality than females adopting any other social strategy. Within a given year, females had a higher risk of death if they were strongly bonded with partners that changed from the previous year versus with partners that remained consistent. Dominance rank, number of adult female groupmates, and age at first reproduction did not predict the risk of death. This study demonstrates that costs and benefits of strong social bonds can be context-dependent, relating to the consistency of social partners over time. We categorized adult female blue monkeys according to the strength and consistency over time of their closest social ties. Females that had strong but inconsistent ties had a higher risk of death than females in all other categories. Social dominance rank, group size, and life history strategies did not influence mortality.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 22
    Publication Date: 2018-01-05
    Description: Expansion of oil palm agriculture is currently one of the main drivers of habitat modification in Southeast Asia. Habitat modification can have significant effects on biodiversity, ecosystem function, and interactions between species by altering species abundances or the available resources in an ecosystem. Increasing complexity within modified habitats has the potential to maintain biodiversity and preserve species interactions. We investigated trophic interactions between Argyrodes miniaceus, a cleptoparasitic spider, and its Nephila spp . spider hosts in mature oil palm plantations in Sumatra, Indonesia. A. miniaceus co-occupy the webs of Nephila spp . females and survive by stealing prey items caught in the web. We examined the effects of experimentally manipulated understory vegetation complexity on the density and abundance of A. miniaceus in Nephila spp . webs. Experimental understory treatments included enhanced complexity, standard complexity, and reduced complexity understory vegetation, which had been established as part of the ongoing Biodiversity and Ecosystem Function in Tropical Agriculture (BEFTA) Project. A. miniaceus density ranged from 14.4 to 31.4 spiders per square meter of web, with significantly lower densities found in reduced vegetation complexity treatments compared with both enhanced and standard treatment plots. A. miniaceus abundance per plot was also significantly lower in reduced complexity than in standard and enhanced complexity plots. Synthesis and applications : Maintenance of understory vegetation complexity contributes to the preservation of spider host–cleptoparasite relationships in oil palm plantations. Understory structural complexity in these simplified agroecosystems therefore helps to support abundant spider populations, a functionally important taxon in agricultural landscapes. In addition, management for more structurally complex agricultural habitats can support more complex trophic interactions in tropical agroecosystems. We examined the effects of experimentally manipulated understory vegetation complexity in oil palm plantations on the density and abundance of the cleptoparasitic spider Argyrodes miniaceus in the webs of Nephila spp. spider hosts. A. miniaceus density per web and abundance per plot were significantly lower in reduced vegetation complexity treatments compared with both enhanced and standard treatment plots. Our results suggest that understory structural complexity in simplified tropical agricultural landscapes can help to support abundant spider populations, a functionally important taxon in agricultural landscapes, and can support more complex trophic interactions in tropical agroecosystems.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 23
    Publication Date: 2018-01-04
    Description: ABSTRACT We explored the effect of S100A12 gene on serum levels of anti-inflammatory/pro-inflammatory cytokines in septic rats by activating the extracellular signal-regulated kinase (ERK) signaling pathway. A total of 180 specific pathogen-free (SPF) rats were purchased to establish cecal ligation and puncture (CLP) model. Rats were assigned into the sham, model, empty vector, S100A12 siRNA, epidermal growth factor (EGF) and S100A12 siRNA + EGF groups. The expressions of S100A12, ERK-1, ERK-2, cPLA2 and NF-κB in liver tissues of rats among six groups were detected by RT-qPCR and western blotting. ELISA was used to determine serum levels of IL-1β, IL-10, TNF-α, procalcitonin (PCT) and C-reactive protein (CRP). Pearson correlation analysis was conducted to measure correlations. Cell apoptosis of rats among six groups was detected by Tunel staining. The expressions of S100A12, ERK-1, ERK-2, cPLA2 and NF-κB decreased in the S100A12 siRNA group while increased in the EGF group compared with the model group. S100A12 mRNA expression was positively correlated with mRNA expressions of related genes in the ERK signaling pathway (ERK-1, ERK-2, cPLA2 and NF-κB) in the model and empty vector groups. Expressions of IL-1β, IL-6, TNF-α, PCT and CRP in the EGF group were higher than those in the model group, but were lower than those in the S100A12 siRNA group. Comparedwith the model group, cell apoptosis decreased in the S100A12 siRNA group but that increased in the EGF group. We demonstrates that S100A12 gene silencing decreases serum levels of anti-inflammatory/pro-inflammatory cytokines in septic rats by inhibiting the ERK signaling pathway. This article is protected by copyright. All rights reserved
    Electronic ISSN: 0091-7419
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 24
    Publication Date: 2018-01-04
    Description: Background Lung perfusion MRI after i.v. gadolinium (Gd) contrast administration is commonly based on spoiled gradient-echo acquisitions, such as volume-interpolated breath-hold examinations (VIBE), suffering from low signal-to-noise in the parenchyma. Purpose To investigate the lung signal enhancement ratio (SER) with ultra-fast steady-state free precession (ufSSFP) after Gd-administration. Study Type Retrospective. Subjects Ten subjects with healthy lungs; nine patients with pulmonary diseases (chronic obstructive pulmonary disease [COPD], lung cancer, pulmonary fibrosis, lung contusion). Field Strength/Sequence VIBE and ufSSFP imaging of the chest was performed at 1.5T before and 3 minutes after i.v. gadobenate dimeglumine. Assessment A workflow including deformable image registration and median filtering was used to compute 3D SER maps. SER was analyzed in the lung, blood pool, liver, muscles, and fat. The artifacts were assessed by a radiologist. In the COPD patients, ufSSFP-SER was compared to 99m Tc-MAA-SPECT/CT by visual scoring of lung enhancement deficits. Statistical Tests Mean signal, standard deviation (SD), intersubject SD, and coefficient of variation (CV) were calculated for SER. Statistical significance of differences in signal and artifacts were determined using Wilcoxon signed-rank paired test. Intermodality agreement between ufSSFP-SER and SPECT/CT was calculated by Cohen's kappa (κ q ). Results In healthy lungs, ufSSFP-SER (99% ± 23%, mean ± pooled intrasubject SD, CV = 23%) was significantly higher ( P  〈 10 −3 ) and more homogeneous ( P  〈 10 −3 ) than VIBE (47% ± 26%, CV = 57%). UfSSFP-SER was significantly higher ( P  〈 10 −3 ) for the lungs (99% ± 9%, mean ± intersubject SD) than for the blood (81% ± 7%) and other tissues (liver 33% ± 8%, muscle 26% ± 5%, fat 2% ± 1%). In the lung ufSSFP-SER exhibits homogeneity on iso-gravitational planes, and an anterior–posterior gradient. In COPD patients, ufSSFP-SER was reduced and less homogeneous compared to the control group (73% ± 33%, mean ± pooled intrasubject SD, CV = 42%). ufSSFP-SER had moderate intermodality agreement with SPECT/CT (κ q  = 0.64). Data Conclusion UfSSFP-SER of the lung is a rapid and simple method. Our preliminary data show plausible results in different pulmonary diseases, motivating further evaluation in larger cohorts. Level of Evidence : 2 Technical Efficacy : Stage 2 J. Magn. Reson. Imaging 2018.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
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  • 25
    Publication Date: 2018-01-04
    Description: Background High-grade gliomas (HGGs) induce both vasogenic edema and extensive infiltration of tumor cells, both of which present with similar appearance on conventional MRI. Using current radiological criteria, differentiation between these tumoral and nontumoral areas within the nonenhancing lesion area remains challenging. Purpose To use radiomics patch-based analysis, based on conventional MRI, for the classification of the nonenhancing lesion area in patients with HGG into tumoral and nontumoral components. Study Type Prospective. Subjects In all, 179 MRI scans were obtained from 102 patients: 67 patients with HGG and 35 patients with brain metastases. A subgroup of 15 patients with HGG were scanned before and following administration of bevacizumab. Field Strength/Sequence Pre and postcontrast agent T 1 -weighted-imaging (WI), T 2 WI, FLAIR, diffusion-tensor-imaging (DTI), and dynamic-contrast-enhanced (DCE)-MRI at 3T. Assessment A total of 225 histograms and gray-level-co-occurrence matrix-based features were extracted from the nonenhancing lesion area. Tumoral volumes of interest (VOIs) were defined at the peritumoral area in patients with HGG; nontumoral VOIs were defined in patients with brain metastasis. Twenty machine-learning algorithms including support-vector-machine (SVM), k-nearest neighbor, decision-trees, and ensemble classifiers were tested. The best classifier was trained on the entire labeled data, and was used to classify the entire data. Statistical Tests Dimensional reduction was performed on the 225 features using principal component analysis. Classification results were evaluated based on the sensitivity, specificity, and accuracy of each of the 20 classifiers, first based on a training and testing dataset (80% of the labeled data) in a 5-fold manner, and next by applying the best classifier to the validation data (the remaining 20% of the labeled data). Results were additionally evaluated by assessing differences in dynamic-contrast-enhanced plasma-volume ( v p ) and volume-transfer-constant ( k trans ) values between the two components using Mann–Whitney U -test/ t -test. Results The best classification into tumoral and nontumoral lesion components was obtained using a linear SVM classifier, with average accuracy of 87%, sensitivity 86%, and specificity of 89% (for the training and testing data). Significantly higher v p and k trans values ( P 〈 0.0001) were detected in the tumoral compared to the nontumoral component. Preliminary classification results in a subgroup of patients treated with bevacizumab demonstrated a reduction mainly in the nontumoral component following administration of bevacizumab, enabling early assessment of disease progression in some patients. Data Conclusion A radiomics patch-based analysis enables classification of the nonenhancing lesion area in patients with HGG. Preliminary results were promising and the proposed method has the potential to assist in clinical decision-making and to improve therapy response assessment in patients with HGG. Level of Evidence : 1 Technical Efficacy Stage 4 J. Magn. Reson. Imaging 2018.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
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  • 26
    Publication Date: 2018-01-04
    Description: Background Since definitive concurrent chemoradiotherapy (CRT) is standard therapy for inoperable esophageal squamous cell carcinoma (ESCC), early evaluation of treatment response is crucial for patients and would be useful in assessing response, especially in patients with severe side effects. Purpose To explore the feasibility of intravoxel incoherent motion (IVIM) MRI in the early assessment of treatment response to CRT. Study Type Prospective. Population Twenty-three inoperable ESCC patients. Sequence IVIM 3T MRI of nine b values (0, 25, 50, 75, 100, 150, 200, 500 and 800 s/mm 2 ) was performed at four timepoints: pre-CRT (within 5 days before CRT), mid-CRT (2–3 weeks after the start of CRT), end-CRT (within 5 days after the end of CRT), and post-CRT (1 month after the end of CRT). Assessment IVIM-based parameters and ADC were analyzed independently by two radiologists and treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Statistical Tests Analyses of variance for repeated measurements were conducted to observe dynamic changes of IVIM-based parameters (D, f, and D*) and ADC during CRT. The parameters and their change percentages (Δ%) were compared between complete response (CR) and partial response (PR) by Mann–Whitney U -test. Diagnostic performance of parameters in predicting response was tested with receiver-operating characteristic curve analysis. Results ADC, D, and f increased significantly during CRT ( P  〈 0.001, 〈 0.001, and 0.001, respectively). ADC, f, Δ%ADC, and Δ%D at mid-CRT in CR group were significantly higher than those in the PR group ( P  = 0.002, 0.013, 0.005, and 0.011, respectively). D combined with f and ADC had highest area under curve (0.917) in identifying CR from PR. Data Conclusion IVIM parameters proved useful in assessing response to definitive concurrent CRT for inoperable ESCC and combined with ADC at an early stage of treatment was a good predictor of response. Level of Evidence : 2 Technical Efficacy : Stage 4 J. Magn. Reson. Imaging 2018.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
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  • 27
    Publication Date: 2018-01-05
    Description: Previous case-control studies have suggested that atopic allergic conditions (AACs) are inversely associated with pancreatic cancer, but this relationship has not been supported in many prospective settings. In this study, we investigated the influence of AACs (asthma, hay fever, or allergy) and the treatment of these conditions on pancreatic cancer risk among participants of the Multiethnic Cohort Study (MEC). AACs and antihistamine use were assessed via a baseline questionnaire when participants joined the MEC in 1993-1996. Risk ratios (RRs) and 95% confidence intervals (CIs) for pancreatic cancer incidence by AACs and antihistamines were calculated using Cox regression, adjusting for age, sex, ethnicity, education, smoking status, family history of pancreatic cancer, body mass index, diabetes, and alcohol intake. We further evaluated associations among subgroups defined by age, sex, ethnicity, follow-up time and known pancreatic cancer risk factors. During an average 16-year follow-up, 1,455 incident cases of pancreatic cancer were identified among 187,226 white, African American, Latino, Japanese American and Native Hawaiian men and women. AACs (RR 1.00, 95% CI 0.88-1.12) and antihistamines (RR 0.92, 95% CI 0.78-1.07) were not clearly associated with pancreatic cancer incidence. While these associations were also null for most subgroups, we did observe protective associations of AACs (RR 0.74, 95% CI 0.56-0.98) and antihistamines (RR 0.66, 95% CI 0.45-0.96) among the oldest participants (70+). Our results, in agreement with past prospective studies, suggest that AACs are not associated with pancreatic cancer in general, but the observed protective associations among the oldest age group may warrant future investigation. This article is protected by copyright. All rights reserved.
    Print ISSN: 0020-7136
    Electronic ISSN: 1097-0215
    Topics: Biology , Medicine
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  • 28
    Publication Date: 2018-01-06
    Description: While long-term survival rates for early-stage lung cancer are high, most cases are diagnosed in later stages that can negatively impact survival rates. We aim to design a simple, single biomarker blood test for early-stage lung cancer that is robust to preclinical variables and can be readily implemented in the clinic. Whole blood was collected in PAXgene tubes from a training set of 29 patients, and a validation set of 260 patients, of which samples from 58 patients were prospectively collected in a clinical trial specifically for this study. After RNA was extracted, the expression of FPR1 and a reference gene were quantified by an automated one-step Taqman RT-PCR assay. Elevated levels of FPR1 mRNA in whole blood predicted lung cancer status with a sensitivity of 55% and a specificity of 87% on all validation specimens. The prospectively collected specimens had a significantly higher 68% sensitivity and 89% specificity. Results from patients with benign nodules were similar to healthy volunteers. No meaningful correlation was present between our test results and any clinical characteristic other than lung cancer diagnosis. FPR1 mRNA levels in whole blood can predict the presence of lung cancer. Using this as a reflex test for positive lung cancer screening computed tomography (CT) scans has the potential to increase the positive predictive value. This marker can be easily measured in an automated process utilizing off-the-shelf equipment and reagents. Further work is justified to explain the source of this biomarker. This article is protected by copyright. All rights reserved.
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    Electronic ISSN: 1097-0215
    Topics: Biology , Medicine
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  • 29
    Publication Date: 2018-01-06
    Description: A supramolecular solvent composed of decanol in tetrahydrofuran/water was utilized for the simultaneous microextraction of chiral triadimefon and triadimenol in beer samples. Supramolecular solvents are nanostructured amphiphilic liquids that contain aqueous cavities, and the size of those cavities can be adjusted by the ratio of decanol, tetrahydrofuran, and water. The target analytes were mixed into the matrix sample and extracted in the supramolecular solvent phase, which was followed by separation and quantification by chiral liquid chromatography-mass spectrometry. The influences of some analytical parameters and matrix components were all examined. Under the optimized conditions, the method detection limits were in the range of 0.24 to 0.98 μg L −1 (at a signal/noise of 3), with relative standard deviations between 1.6 and 5.7%. The linearities of the calibration plots were between 0.5 to 50 (triadimenol) and 1.0 to 100 μg L −1 (triadimefon). When this method was applied to a spiked beer sample, the recoveries ranged from 84 to 100%.
    Print ISSN: 0899-0042
    Electronic ISSN: 1520-636X
    Topics: Chemistry and Pharmacology
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  • 30
    Publication Date: 2018-01-06
    Description: Carrion beetles, Nicrophorus vespilloides, are reared on decomposing carrion where larvae are exposed to high populations of carcass-derived bacteria. Larvae do not become colonized with these bacteria but instead are colonized with the gut microbiome of their parents, suggesting that bacteria in the beetle microbiome outcompete the carcass-derived species for larval colonization. Here, we test this hypothesis and quantify the fitness consequences of colonization with different bacterial symbionts. First, we show that beetles colonized by their endogenous microbiome produce heavier broods than those colonized with carcass-bacteria. Next, we show that bacteria from the endogenous microbiome, including Providencia rettgeri and Morganella morganii , are better colonizers of the beetle gut and can outcompete nonendogenous species, including Serratia marcescens and Escherichia coli , during in vivo competition. Finally, we find that Providencia and Morganella provide beetles with colonization resistance against Serratia and thereby reduce Serratia -induced larval mortality. This effect is eliminated in larvae first colonized by Serratia , suggesting that while competition within the larval gut is determined by priority effects, these effects are less important for Serratia -induced mortality. Our work suggests that an unappreciated benefit of parental care in N. vespilloides is the social transmission of the microbiome from parents to offspring. Our work supports the idea that bacterial gut symbionts provide direct fitness benefits to Nicrophorus larvae by outcompeting potential bacterial pathogens. They further suggest that one benefit of parental care in Nicrophorus vespilloides is the social transmission of the microbiome from caring parents to their offspring.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 31
    Publication Date: 2018-01-06
    Description: Mitochondrial defects and anti-mitochondrial cardiolipin (CL) antibodies are frequently detected in autoimmune disease patients. CL from dysregulated mitochondria activates various pattern recognition receptors, such as NLRP3. However, the mechanism by which mitochondrial CL activates antigen-presenting cells (APCs) as a damage-associated molecular pattern to prime antigen-specific naïve T cells, which is crucial for T-cell-dependent anti-cardiolipin IgG antibody production in autoimmune diseases is unelucidated. Here we show, that CL increases the expression of costimulatory molecules in CD11c + APCs both in vitro and in vivo. CL activates CD11c + APCs via TLR2-PI3K-PKN1-AKT/p38MAPK-NF-κB signaling. CD11c + APCs that have been activated by CL are sufficient to prime H-Y peptide-specific naïve CD4 + T cells and OVA-specific naïve CD8 + T cells. TLR2 is necessary for anti-CL IgG antibody responses in vivo. Intraperitoneal injection of CL does not activate CD11c + APCs in CD14 KO mice to the same extent as in wild-type mice. CL binds to CD14 (Kd = 7 × 10 −7 M). CD14, but not MD2, plays a role in NF-kB activation by CL, suggesting that CD14 + macrophages contribute to recognizing CL. In summary, CL activates signaling pathways in CD11c + APCs through a mechanism similar to gram (+) bacteria and plays a crucial role in priming antigen-specific naïve T cells. This article is protected by copyright. All rights reserved
    Print ISSN: 0014-2980
    Electronic ISSN: 1521-4141
    Topics: Medicine
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  • 32
    Publication Date: 2018-01-06
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
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  • 33
    Publication Date: 2018-01-06
    Description: Glioblastomas (GBM) are high-grade brain tumours, differentially driven by alterations (amplification, deletion, or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12-15 months following standard therapy. A combination of interventions targeting tumor-specific cell surface regulators along with convergent downstream signalling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy. An EGFR-specific affibody (Z EGFR:03115 ) was conjugated to the phthalocyanine dye, IR700DX, which when excited with near-infrared light produces a cytotoxic response. Z EGFR:03115 -IR700DX EGFR-specific binding was confirmed by FACS analysis and confocal microscopy. The conjugate showed effective targeting of EGFR positive GBM cells in the brain. The therapeutic potential of the conjugate was assessed both in vitro, in GBM cell lines and spheroids by the CellTiter-Glo® assay, and in vivo using subcutaneous U87-MGvIII xenografts. In addition, mice were imaged pre- and post-PIT using the IVIS/Spectrum/CT to monitor treatment response. Binding of the conjugate correlated to the level of EGFR expression in GBM cell lines. The cell proliferation assay revealed a receptor-dependent response between the tested cell lines. Inhibition of EGFRvIII+ve tumor growth was observed following administration of the immunoconjugate and irradiation. Importantly, this response was not seen in control tumors. In conclusion, the Z EGFR:03115 -IR700DX showed specific uptake in vitro and enabled imaging of EGFR expression in the orthotopic brain tumor model. Moreover, the proof-of-concept in vivo PIT study demonstrated therapeutic efficacy of the conjugate in subcutaneous glioma xenografts. This article is protected by copyright. All rights reserved.
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    Electronic ISSN: 1097-0215
    Topics: Biology , Medicine
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  • 34
    Publication Date: 2018-01-06
    Description: Background Selenium status is inversely associated with the incidence of prostate cancer. However, supplementation trials have not indicated a benefit of selenium supplementation in reducing cancer risk. Polymorphisms in the gene encoding selenoprotein 15 (SELENOF) are associated with cancer incidence/mortality and present disproportionately in African Americans. Relationships among the genotype of selenoproteins implicated in increased cancer risk, selenium status, and race with prostate cancer were investigated. Methods Tissue microarrays were used to assess SELENOF levels and cellular location in prostatic tissue. Sera and DNA from participants of the Chicago-based Adiposity Study Cohort were used to quantify selenium levels and genotype frequencies of the genes for SELENOF and the selenium-carrier protein selenoprotein P (SELENOP). Logistic regression models for dichotomous patient outcomes and regression models for continuous outcome were employed to identify both clinical, genetic, and biochemical characteristics that are associated with these outcomes. Results SELENOF is dramatically reduced in prostate cancer and lower in tumors derived from African American men as compared to tumors obtained from Caucasians. Differing frequency of SELENOF polymorphisms and lower selenium levels were observed in African Americans as compared to Caucasians. SELENOF genotypes were associated with higher histological tumor grade. A polymorphism in SELENOP was associated with recurrence and higher serum PSA. Conclusions These results indicate an interaction between selenium status and selenoprotein genotypes that may contribute to the disparity in prostate cancer incidence and outcome experienced by African Americans.
    Print ISSN: 0270-4137
    Electronic ISSN: 1097-0045
    Topics: Medicine
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  • 35
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    Wiley-Blackwell
    Publication Date: 2018-01-06
    Description: Tumour heterogeneity is an important feature of colorectal cancer (CRC) manifested by dynamic changes in gene expression, protein expression, and availability of different tumour subtypes. Recent publications in the past ten years have revealed proteome heterogeneity between different colorectal tumours and within the same tumour site. This paper reviews recent research works on the proteome heterogeneity in CRC, which includes the heterogeneity within a single tumour (intratumour heterogeneity), between different anatomical sites at the same organ, and between primary and metastatic sites (intertumour heterogeneity). The potential use of proteome heterogeneity in precision medicine and its implications in biomarker discovery and therapeutic outcomes will be discussed. Identification of the unique proteome landscape between and within individual tumours is imperative for understanding cancer biology and the management of CRC patients. This article is protected by copyright. All rights reserved
    Print ISSN: 1615-9853
    Electronic ISSN: 1615-9861
    Topics: Medicine
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  • 36
    Publication Date: 2018-01-06
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
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  • 37
    Publication Date: 2018-01-06
    Description: During development, the endoderm initiates organ-restricted gene expression patterns in a spatiotemporally controlled manner. This process, termed induction, requires signals from adjacent mesodermal derivatives. Fibroblast Growth Factor (FGF) and Bone Morphogenetic Protein (BMP) emanating from the cardiac mesoderm and the septum transversum mesenchyme (STM), respectively, are believed to be simultaneously and uniformly required to directly induce hepatic gene expression from the murine endoderm. Using small molecule inhibitors of BMP signals during liver bud induction in the developing mouse embryo, we find that BMP signaling is not uniformly required to induce hepatic gene expression. Although BMP inhibition causes an overall reduction in the number of induced hepatoblasts, the STM-bounded posterior liver bud demonstrates the most severe loss of the essential hepatic transcription factor Hepatocyte nuclear factor 4-α (HNF4α) while the sinus venosus (SV)-lined anterior liver bud is less affected. We find that the posterior liver bud progenitors are anteriorly displaced and aberrantly activate pancreatobiliary markers including SOX9. Additionally, we find that ectopically expressed SOX9 inhibits HNF4α and that BMP is indirectly required for hepatoblast induction. Finally, because previous work demonstrated that FGF signals were essential for anterior but not posterior liver bud induction, we examined synchronous BMP and FGF inhibition and find that this leads to a massive loss of induced hepatoblasts. Conclusions: BMP signaling is required to maintain the hepato-pancreatobiliary boundary, at least in part, by indirectly repressing SOX9 in the hepatic endoderm. BMP and FGF signals are each required for the induction of spatially complementary subsets of hepatoblasts. These results highlight the importance of studying early inductive processes in the whole embryo. This article is protected by copyright. All rights reserved.
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  • 38
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    Wiley-Blackwell
    Publication Date: 2018-01-06
    Print ISSN: 1066-5099
    Electronic ISSN: 1549-4918
    Topics: Medicine
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  • 39
    Publication Date: 2018-01-07
    Description: Currently published studies have implicated that microRNAs (miRNAs) including exosomes-encapsulated miRNAs play a critical role in rheumatoid arthritis (RA). Previously, we have found that exosomes-encapsulated miR-548a-3p was significantly decreased in serum samples from RA patients by miRNAs microarray analysis. However, little is known of the role of miR-548a-3p in the development and progression of RA. In this study, we aim to investigate the underlying molecular mechanisms of miR-548a-3p in RA, which will provide new insight into understanding the pathogenesis of RA and identifying novel therapeutics targets for this disease. As validated by quantitative real-time polymerase chain reaction (qRT-PCR), the expression of miR-548a-3p in serum exosomes and peripheral blood mononuclear cells (PBMCs) of RA patients (n = 76) was obviously down-regulated compared with healthy controls (n = 20). Serum exosomal miR-548a-3p was negatively associated with levels of CRP, RF and ESR in serum of patients with RA. MiR-548a-3p could inhibit the proliferation and activation of pTHP-1 cells by regulating the TLR4/NF-κB signaling pathway. Accordingly, exosomes-delivered miR-548a-3p may be a critical factor predicting the disease activity of RA. MiR-548a-3p/TLR4/NF-κB axis can serve as promising targets for RA diagnosis and treatment. This article is protected by copyright. All rights reserved
    Electronic ISSN: 0091-7419
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 40
    Publication Date: 2018-01-09
    Description: We report a multicentre retrospective study that analysed clinical characteristics and outcomes in 117 patients with primary plasma cell leukaemia (pPCL) treated at the participating institutions between January 2006 and December 2016. The median age at the time of pPCL diagnosis was 61 years. Ninety-eight patients were treated with novel agents, with an overall response rate of 78%. Fifty-five patients (64%) patients underwent upfront autologous stem cell transplantation (ASCT). The median follow-up time was 50 months (95% confidence interval [CI] 33; 76), with a median overall survival (OS) for the entire group of 23 months (95% CI 15; 34). The median OS time in patients who underwent upfront ASCT was 35 months (95% CI 24·3; 46) as compared to 13 months (95% CI 6·3; 35·8) in patients who did not receive ASCT ( P  =   0·001). Multivariate analyses identified age ≥60 years, platelet count ≤100 × 10 9 /l and peripheral blood plasma cell count ≥20 × 10 9 /l as independent predictors of worse survival. The median OS in patients with 0, 1 or 2–3 of these risk factors was 46, 27 and 12 months, respectively ( P  〈   0·001). Our findings support the use of novel agents and ASCT as frontline treatment in patients with pPCL. The constructed prognostic score should be independently validated.
    Print ISSN: 0007-1048
    Electronic ISSN: 1365-2141
    Topics: Medicine
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  • 41
    Publication Date: 2018-01-09
    Description: BACKGROUND To the authors' knowledge, the practice patterns for patients aged more than 80 years with stage III non-small cell lung cancer (NSCLC) is not well known. The purpose of the current study was to investigate factors predictive of and the impact on overall survival (OS) after concurrent chemoradiation (CRT) among patients aged ≥80 years with American Joint Committee on Cancer stage III NSCLC in the National Cancer Data Base (NCDB). METHODS In the NCDB, patients aged ≥80 years who were diagnosed with stage III NSCLC from 2004 to 2013 with complete treatment records were identified. Multivariable logistic regression and Cox proportional hazard models were generated and propensity score-matched analysis was used. RESULTS A total of 12,641 patients met the entry criteria: 6018 (47.6%) had stage IIIA disease and 6623 (52.4%) had stage IIIB disease. The median age at the time of diagnosis was 83.0 years (range, 80-91 years). A total of 7921 patients (62.7%) received no therapy. Black race (odds ratio [OR], 1.23; 95% confidence interval [95% CI], 1.06-1.43) and living in a lower educated census tract of residence (OR, 1.20; 95% CI, 1.03-1.40) were found to be associated with not receiving care, whereas treatment at an academic center (OR, 0.80; 95% CI, 0.70-0.92) was associated with receiving cancer-directed therapy. Receipt of no treatment (hazard ratio [HR], 2.69; 95% CI, 2.57-2.82) or definitive radiation alone (HR, 1.15; 95% CI, 1.07-1.24) compared with CRT was associated with worse OS. On propensity score matching, not receiving CRT was found to be associated with worse OS (HR, 1.58; 95% CI, 1.44-1.72). CONCLUSIONS In this NCDB analysis, approximately 62.7% of patients aged ≥80 years with stage III NSCLC received no cancer-directed care. Black race and living in a lower educated census tract were associated with not receiving cancer-directed care. OS was found to be improved in patients receiving CRT. Cancer 2018 . © 2018 American Cancer Society .
    Print ISSN: 0008-543X
    Electronic ISSN: 1097-0142
    Topics: Biology , Medicine
    Published by Wiley-Blackwell on behalf of The American Cancer Society.
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  • 42
    Publication Date: 2018-01-09
    Print ISSN: 0007-1048
    Electronic ISSN: 1365-2141
    Topics: Medicine
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  • 43
    Publication Date: 2018-01-09
    Description: With increasing attention being paid to the consequences of global biodiversity losses, several recent studies have demonstrated that realistic species losses can have larger impacts than random species losses on community productivity and resilience. However, little is known about the effects of the order in which species are lost on biodiversity–disease relationships. Using a multiyear nitrogen addition and artificial warming experiment in natural assemblages of alpine meadow vegetation on the Qinghai-Tibetan Plateau, we inferred the sequence of plant species losses under fertilization/warming. Then the sequence of species losses under fertilization/warming was used to simulate the species loss orders (both realistic and random) in an adjacently novel removal experiment manipulating plot-level plant diversity. We explicitly compared the effect sizes of random versus realistic species losses simulated from fertilization/warming on plant foliar fungal diseases. We found that realistic species losses simulated from fertilization had greater effects than random losses on fungal diseases, and that species identity drove the diversity–disease relationship. Moreover, the plant species most prone to foliar fungal diseases were also the least vulnerable to extinction under fertilization, demonstrating the importance of protecting low competence species (the ability to maintain and transmit fungal infections was low) to impede the spread of infectious disease. In contrast, there was no difference between random and realistic species loss scenarios simulated from experimental warming (or the combination of warming and fertilization) on the diversity–disease relationship, indicating that the functional consequences of species losses may vary under different drivers. Most manipulative biodiversity–ecosystem function (BEF) experiments use randomly constructed species assemblages. We took a novel approach to explicitly compare dilution effects on foliar fungal infections for random versus realistic species losses simulated from nitrogen addition and warming treatments. We found that realistic species losses under fertilization had greater effects than random losses on fungal diseases.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 44
    Publication Date: 2018-01-09
    Description: Understanding local adaptation of tree populations to climate allows the development of assisted migration guidelines as a tool for forest managers to address climate change. Here, we study the relationship among climate, a wide range of physiological traits, and field performance of selected white spruce provenances originating from throughout the species range. Tree height, survival, cold hardiness, hydraulic, and wood anatomical traits were measured in a 32-year-old common garden trial, located in the center of the species range. Provenance performance included all combinations of high versus low survival and growth, with the most prevalent population differentiation for adaptive traits observed in cold hardiness. Cold hardiness showed a strong association with survival and was associated with cold winter temperatures at the site of seed origin. Tree height was mostly explained by the length of the growing season at the origin of the seed source. Although population differentiation was generally weak in wood anatomical and hydraulic traits, within-population variation was substantial in some traits, and a boundary analysis revealed that efficient water transport was associated with vulnerable xylem and low wood density, indicating that an optimal combination of high water transport efficiency and high cavitation resistance is not possible. Our results suggest that assisted migration prescriptions may be advantageous under warming climate, but pronounced trade-offs between survival and cold hardiness require a careful consideration of the distances of these transfers. In this study, we study relationships between climate, a wide range of physiological traits, and field performance of selected white spruce provenances in a common garden. We observed a strong influence of fall hardiness in tree mortality while tree growth was mostly explained by growing season length. These results will help develop assisted migration prescriptions to mitigate the climate change impact in our forests.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 45
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    Wiley-Blackwell
    Publication Date: 2018-01-09
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 46
    Publication Date: 2018-01-09
    Description: Deposition of amyloid-β (Aβ) as senile plaques is one of the pathological hallmarks in the brains of Alzheimer's disease (AD) patients. In addition, glial activation has been found in AD brains, although the precise pathological role of astrocytes remains unclear. Here, we identified kallikrein-related peptidase 7 (KLK7) as an astrocyte-derived Aβ degrading enzyme. Expression of KLK7 mRNA was significantly decreased in the brains of AD patients. Ablation of Klk7 exacerbated the thioflavin S-positive Aβ pathology in AD model mice. The expression of Klk7 was upregulated by Aβ treatment in the primary astrocyte, suggesting that Klk7 is homeostatically modulated by Aβ-induced responses. Finally, we found that the Food and Drug Administration-approved anti-dementia drug memantine can increase the expression of Klk7 and Aβ degradation activity specifically in the astrocytes. These data suggest that KLK7 is an important enzyme in the degradation and clearance of deposited Aβ species by astrocytes involved in the pathogenesis of AD. Decreased clearance of Aβ from the brain is related to the pathogenesis of Alzheimer's disease (AD). Kallikrein-related peptidase 7 (KLK7) is an astrocyte-derived Aβ degrading enzyme that affects the amyloid pathology. Thus, astrocytes could be an effective cellular target for AD.
    Print ISSN: 1757-4676
    Electronic ISSN: 1757-4684
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  • 47
    Publication Date: 2018-01-09
    Description: Plant species affect soil bacterial diversity and compositions. However, little is known about the role of dominant plant species in shaping the soil bacterial community during the restoration of sandy grasslands in Horqin Sandy Land, northern China. We established a mesocosm pots experiment to investigate short-term responses of soil bacterial diversity and composition, and the related soil properties in degraded soils without vegetation (bare sand as the control, CK) to restoration with five plant species that dominate across restoration stages: Agriophyllum squarrosum (AS), Artemisia halodendron (AH), Setaria viridis (SV), Chenopodium acuminatum (CA), and Corispermum macrocarpum (CM). We used redundancy analysis (RDA) to analyze the association between soil bacterial composition and soil properties in different plant species. Our results indicated that soil bacterial diversity was significantly lower in vegetated soils independent of plant species than in the CK. Specifically, soil bacterial species richness and diversity were lower under the shrub AH and the herbaceous plants AS, SV, and CA, and soil bacterial abundance was lower under AH compared with the CK. A field investigation confirmed the same trends where soil bacteria diversity was lower under AS and AH than in bare sand. The high-sequence annotation analysis showed that Proteobacteria , Actinobacteria, and Bacteroidetes were the most common phyla in sandy land irrespective of soil plant cover. The OTUs (operational taxonomic units) indicated that some bacterial species were specific to the host plants. Relative to bare sand (CK), soils with vegetative cover exhibited lower soil water content and temperature, and higher soil carbon and nitrogen contents. The RDA result indicated that, in addition to plant species, soil water and nitrogen contents were the most important factors shaping soil bacterial composition in semiarid sandy land. Our study from the pot and field investigations clearly demonstrated that planting dominant species in bare sand impacts bacterial diversity. In semiarid ecosystems, changes in the dominant plant species during vegetation restoration efforts can affect the soil bacterial diversity and composition through the direct effects of plants and the indirect effects of soil properties that are driven by plant species. In addition to plant species, soil water and nitrogen contents were the most important factors shaping soil bacterial composition in semiarid sandy land. Our study from the pot and field investigations clearly demonstrated that planting dominant species in bare sand impacts bacterial diversity. In semiarid ecosystems, changes in the dominant plant species during vegetation restoration efforts can affect the soil bacterial diversity and composition through the direct effects of plants and the indirect effects of soil properties that are driven by plant species.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 48
    Publication Date: 2018-01-09
    Description: Peripheral myelin protein 22 (PMP22) is a component of compact myelin in the peripheral nervous system. The amount of PMP22 in myelin is tightly regulated, and PMP22 over or under-expression cause Charcot-Marie-Tooth 1A (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP). Despite the importance of PMP22 , its function remains largely unknown. It was reported that PMP22 interacts with the β4 subunit of the laminin receptor α6β4 integrin, suggesting that α6β4 integrin and laminins may contribute to the pathogenesis of CMT1A or HNPP. Here we asked if the lack of α6β4 integrin in Schwann cells influences myelin stability in the HNPP mouse model. Our data indicate that PMP22 and β4 integrin may not interact directly in myelinating Schwann cells, however, ablating β4 integrin delays the formation of tomacula, a characteristic feature of HNPP. In contrast, ablation of integrin β4 worsens nerve conduction velocities and non-compact myelin organization in HNPP animals. This study demonstrates that indirect interactions between an extracellular matrix receptor and a myelin protein influence the stability and function of myelinated fibers. This article is protected by copyright. All rights reserved.
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    Electronic ISSN: 1471-4159
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  • 49
    Publication Date: 2018-01-09
    Description: The attribution of incentive salience to reward-predictive stimuli has been shown to be associated with substance abuse-like behavior such as increased drug taking. Evidence suggests that glutamate neurotransmission and sequential N-methyl-D-aspartate (NMDA) activation are involved in the attribution of incentive salience. Here we further explore the role of second-by-second glutamate neurotransmission in the attribution of incentive salience to reward-predictive stimuli by measuring sign-tracking behavior during a Pavlovian conditioned approach procedure using ceramic-based microelectrode arrays configured for sensitive measures of extracellular glutamate in awake behaving Sprague Dawley rats. Specifically, we show that there is an increase in extracellular glutamate levels in the prelimbic cortex (PrL) and the nucleus accumbens core (NAcC) during sign-tracking behavior to a food-predictive conditioned stimulus (CS+) compared to the presentation of a non-predictive conditioned stimulus (CS-). Further, the results indicate greater increases in extracellular glutamate levels in the PrL compared to NAcC in response to the CS+, including differences in glutamate release and signal decay. Taken together, the present research suggests that there is differential glutamate signaling in the NAcC and PrL during sign-tracking behavior to a food-predictive CS+. This article is protected by copyright. All rights reserved.
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  • 50
    Publication Date: 2018-01-09
    Description: Loss of function mutations of DJ-1 ( PARK7 ) have been linked to the pathogenesis of Parkinson disease (PD). Antioxidative stress is one of the multi-protective functions of DJ-1, and oxidation of cysteine 106 (Cys106) has been proposed to regulate the protective activity of DJ-1. Uncoupling protein 4 (UCP4) is located in the inner membrane of mitochondria and functions to protect against oxidative stress. In this study, we used neuronal (SH-SY5Y) cells and DJ-1 knockout (KO) mice to elucidate whether DJ-1 regulated oxidative stress via modulating the expression of UCP4, and the underlying mechanism. The downstream products of oxidative stress, mitochondrial membrane potential (ΔΨm) and cell viability were also investigated. We found that UCP4 was up regulated upon 1-methyl-4-phenylpyridinium (MPP + ) stimulation in SH-SY5Y cells, which was enhanced by wild type DJ-1 and alleviated by DJ-1 knockdown. Expression of UCP4 in DJ-1 KO mice was lower compared with wild type mice. In addition, up-regulation of UCP4 was alleviated by inhibition of oxidized DJ-1, and enhanced by increase of oxidized DJ-1 under conditions of oxidative stress using western blot analysis. Moreover, overexpression of UCP4 in DJ-1 knockdown cells partially reversed the decrease of cell viability, ΔΨm, as well as the increase of products of oxidative stress upon MPP + stimulation. Further analysis showed that DJ-1 regulated transcriptional activity of UCP4 partially via Nuclear factor-kappa B (NF-κB) pathway in the presence of MPP + . Together, our results suggested DJ-1 might regulate the expression of UCP4 by oxidation of DJ-1 and partially via NF-κB pathway in its protective response to oxidative stress. This article is protected by copyright. All rights reserved.
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  • 51
    Publication Date: 2018-01-09
    Description: Purpose To evaluate the role of true diffusion and flow-related pseudodiffusion in cerebral blood flow (CBF) quantification using arterial spin labeling (ASL) with single-shot or segmented 3D gradient and spin echo (GRASE) readouts. Theory The extended phase graph (EPG) algorithm, originally designed to model the effects of T 1 /T 2 relaxation and true diffusion in MRI acquisitions utilizing multiple refocusing RF pulses, was augmented (aEPG). This augmentation accounted for flow-related pseudodiffusion attenuation of intravascular MRI signal in the k-space domain during 3D-GRASE acquisition, which leads to blur along the partition direction in the image domain. Blurring of ASL signal into neighboring voxels can lead to underestimation of CBF in small, high-flow structures such as cortical gray matter (GM). Methods The diffusion sensitivity of 3D-GRASE was evaluated through aEPG simulations and in vivo experiments in 13 healthy subjects. The CBF estimation bias for different postlabeling delays, crusher gradient strengths, and segmentation factors along the partition (PAR) and phase-encoding (PE) directions was numerically assessed by simulations and experimentally validated. Results In vivo experiments demonstrated systematic underestimation of mean GM CBF measured with segmented 3D-GRASE. The GM CBF underestimation depended on ASL preparation and imaging parameters; it reached up to 25% at low-segmentation schemes (1 PAR  × 2 PE ) but was considerably lower at high-segmentation schemes (4 PAR  × 2 PE or 8 PAR  × 2 PE ). Theoretical predictions showed that conventional T 1 /T 2 relaxation and true diffusion may account for at most ∼25% of GM CBF estimation bias, whereas the pseudodiffusion effect constituted the major fraction in a typical ASL experiment. Conclusion The pseudodiffusion effect leads to considerable estimation bias in ASL-based CBF quantification using 3D-GRASE readouts. This bias can be substantially reduced by increasing the segmentation factors. Magn Reson Med, 2018. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
    Print ISSN: 0740-3194
    Electronic ISSN: 1522-2594
    Topics: Medicine
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  • 52
    Publication Date: 2018-01-09
    Print ISSN: 0270-4137
    Electronic ISSN: 1097-0045
    Topics: Medicine
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  • 53
    Publication Date: 2018-01-10
    Description: BACKGROUND In the United States, certain minority groups have been shown to have inferior cancer outcomes compared with the white majority population. However, to the authors' knowledge, the majority of research has not separated ethnicity from immigration status. The objective of the current study was to determine the impact of ethnicity, independent of immigration status, on cancer outcomes in Chinese and South Asian populations in Ontario, Canada. METHODS The authors conducted a population-based retrospective cohort study using administrative databases in Ontario, Canada. Incident cancer cases were captured in Canadian-born Chinese and South Asian individuals, Chinese and South Asian immigrants, and the general Ontario reference population (non-Chinese/non-South Asian and non-immigrant) between 2000 and 2012. Subjects were followed until death (all-cause and cancer-specific), and Cox proportional hazard models were used to estimate the impact of Chinese and South Asian ethnicity on cancer outcomes after adjusting for explanatory variables. RESULTS A total of 423,678 cancer cases were identified; at total of 6631 cases were identified in Canadian-born Chinese individuals and 2752 cases in Canadian-born South Asian individuals. After adjustment, the rate of all-cause mortality was lower for Canadian-born Chinese (hazard ratio [HR], 0.829; 95% confidence interval [95% CI], 0.795-0.865), Canadian-born South Asian (HR, 0.856; 95% CI, 0.797-0.919), and Chinese immigrant (recent immigrant: HR, 0.661 [95% CI, 0.610-0.716] and non-recent immigrant: HR, 0.853 [95% CI, 0.803-0.906]) populations compared with the general Ontario population. A similar effect was found for cancer-specific mortality. CONCLUSIONS Chinese and South Asian ethnic groups appear to have lower cancer mortalities compared with the general Ontario population. After removing the well-documented protective effect of immigration, Chinese and South Asian ethnicities were found to be associated with a cancer survival advantage in Ontario, Canada. Cancer 2018 . © 2018 American Cancer Society .
    Print ISSN: 0008-543X
    Electronic ISSN: 1097-0142
    Topics: Biology , Medicine
    Published by Wiley-Blackwell on behalf of The American Cancer Society.
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  • 54
    Publication Date: 2018-01-10
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
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  • 55
    Publication Date: 2018-01-10
    Description: ABSTRACT Adenosine 2A receptor (A 2A R) exerts protective roles in endotoxin- and/or ischemia-induced tissue damages. However, the role for A 2A R in non-alcoholic fatty liver disease (NAFLD) remains largely unknown. We sought to examine the effects of global and/or myeloid cell-specific A 2A R disruption on the aspects of obesity-associated NAFLD and to elucidate the underlying mechanisms. Global and/or myeloid cell-specific A 2A R-disrupted mice, as well as control mice were fed a high-fat diet (HFD) to induce NAFLD. Also, bone marrow-derived macrophages and primary mouse hepatocytes were examined for inflammatory and metabolic responses. Upon feeding an HFD, both global A 2A R-disrupted mice and myeloid cell-specific A 2A R-defcient mice revealed increased severity of HFD-induced hepatic steatosis and inflammation compared with their respective control mice. In in vitro experiments, A 2A R-deficient macrophages exhibited increased proinflammatory responses, and enhanced fat deposition of wild-type primary hepatocytes in macrophage-hepatocyte co-cultures. In primary hepatocytes, A 2A R deficiency increased the proinflammatory responses and enhanced the effect of palmitate on stimulating fat deposition. Moreover, A 2A R deficiency significantly increased sterol regulatory element-binding protein 1c (SREBP1c) abundance in livers of fasted mice and in hepatocytes upon nutrient deprivation. In the absence of A 2A R, SREBP1c transcription activity was significantly increased in mouse hepatocytes. Taken together, these results demonstrate that disruption of A 2A R in both macrophage and hepatocytes accounts for increased severity of NAFLD, likely through increasing inflammation and through elevating lipogenic events due to stimulation of SREBP1c expression and transcription activity. This article is protected by copyright. All rights reserved.
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  • 56
    Publication Date: 2018-01-10
    Print ISSN: 0270-9139
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  • 57
    Publication Date: 2018-01-10
    Description: ABSTRACT The role of N 6 -methyladenosine (m 6 A) demethylase Fat Mass and Obesity-associated protein (FTO) in the regulation of chemo-radiotherapy resistance remains largely unknown. Here, we show that the mRNA level of FTO is elevated in cervical squamous cell carcinoma (CSCC) tissues when compared with respective adjacent normal tissues. FTO enhances the chemo-radiotherapy resistance both in vitro and in vivo through regulating expression of β-catenin by reducing m 6 A levels in its mRNA transcripts and in turn increases excision repair cross-complementation group 1 (ERCC1) activity. Clinically, the prognostic value of FTO for overall survival is found to be dependent on β-catenin expression in human CSCC samples. Taken together, these findings uncover a critical function for FTO and its substrate m 6 A in the regulation of chemo-radiotherapy resistance, which may bear potential clinical implications for CSCC treatment. This article is protected by copyright. All rights reserved
    Print ISSN: 0899-1987
    Electronic ISSN: 1098-2744
    Topics: Medicine
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  • 58
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    Publication Date: 2018-01-10
    Description: Front cover: Sphingolipids, and particularly the versatile signalling molecule sphingosine-1-phosphate (S1P) are potent mediators regulating vascular functions such as endothelial barrier integrity. We analyzed changes of the sphingolipid metabolism after LPS injection as a model for septic encephalopathy and brain edema and found profound alterations both systemically with a drop in serum S1P as well as at the level of the blood-brain barrier. Our findings point towards a therapeutic potential of drugs interfering with this pathway as novel approach for the detrimental overwhelming immune response in sepsis. Astrocytes (red, GFAP) in the mouse brain cortex (blue: DAPI-labelled nuclei). Read the full article ‘Alteration of sphingolipid metabolism as a putative mechanism underlying LPS-induced BBB disruption’ by R. Vutukuri, R. Brunkhorst, R.-I. Kestner, L. Hansen, N. F. Bouzas, J. Pfeilschifter, K. Devraj and W. Pfeilschifter ( J. Neurochem . 2018, vol. 144(2), pp. 172–185) on doi: 10.1111/jnc.14236 Read the Editorial Highlight ‘Endotoxemia rocks sphingolipid metabolism at the blood–brain barrier’ on doi: 10.1111/jnc.14246
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  • 59
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    Publication Date: 2018-01-10
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  • 60
    Publication Date: 2018-01-10
    Description: Cluster randomized trials are frequently used in health service evaluation. It is common practice to use an analysis model with a random effect to allow for clustering at the analysis stage. In designs where clusters are exposed to both control and treatment conditions, it may be of interest to examine treatment effect heterogeneity across clusters. In designs where clusters are not exposed to both control and treatment conditions, it can also be of interest to allow heterogeneity in the degree of clustering between arms. These two types of heterogeneity are related. It has been proposed in both parallel cluster trials, stepped-wedge, and other cross-over designs that this heterogeneity can be allowed for by incorporating additional random effect(s) into the model. Here, we show that the choice of model parameterization needs careful consideration as some parameterizations for additional heterogeneity induce unnecessary or implausible assumptions. We suggest more appropriate parameterizations, discuss their relative advantages, and demonstrate the implications of these model choices using a real example of a parallel cluster trial and a simulated stepped-wedge trial.
    Print ISSN: 0277-6715
    Electronic ISSN: 1097-0258
    Topics: Mathematics , Medicine
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  • 61
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    Wiley-Blackwell
    Publication Date: 2018-01-11
    Description: Key Points The DMP-1 study examined women in the United States who were counseled regarding the use of SERMs as part of their regular care. Patient perceptions regarding drug-based therapy played an important role in the choice of therapy. The findings suggest that HCPs should not only present medical information, but also communicate with patients regarding their beliefs and experiences.
    Print ISSN: 0007-9235
    Electronic ISSN: 1542-4863
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of American Cancer Society.
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  • 62
    Publication Date: 2018-01-11
    Print ISSN: 0007-1048
    Electronic ISSN: 1365-2141
    Topics: Medicine
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  • 63
    Publication Date: 2018-01-11
    Description: Hunting with wire snares is rife within many tropical forest systems, and constitutes one of the severest threats to a wide range of vertebrate taxa. As for all threats, reliable monitoring of snaring levels is critical for assessing the relative effectiveness of management interventions. However, snares pose a particular challenge in terms of tracking spatial or temporal trends in their prevalence because they are extremely difficult to detect, and are typically spread across large, inaccessible areas. As with cryptic animal targets, any approach used to monitor snaring levels must address the issue of imperfect detection, but no standard method exists to do so. We carried out a field experiment in Keo Seima Wildlife Reserve in eastern Cambodia with the following objectives: (1) To estimate the detection probably of wire snares within a tropical forest context, and to investigate how detectability might be affected by habitat type, snare type, or observer. (2) To trial two sets of sampling protocols feasible to implement in a range of challenging field conditions. (3) To conduct a preliminary assessment of two potential analytical approaches to dealing with the resulting snare encounter data. We found that although different observers had no discernible effect on detection probability, detectability did vary between habitat type and snare type. We contend that simple repeated counts carried out at multiple sites and analyzed using binomial mixture models could represent a practical yet robust solution to the problem of monitoring snaring levels both inside and outside of protected areas. This experiment represents an important first step in developing improved methods of threat monitoring, and such methods are greatly needed in southeast Asia, as well as in as many other regions. This study is a field experiment designed to empirically estimate the detectability of wire snares, and potential determinants of this parameter. It was conducted in a protected area in eastern Cambodia.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 64
    Publication Date: 2018-01-11
    Description: Background: Actins are structural components of the cytoskeleton and muscle, and numerous actin isoforms are found in most organisms. However, many actin isoforms are expressed in distinct patterns allowing each actin to have a specialized function. Numerous studies have demonstrated that actin isoforms both can and cannot compensate for each other under specific circumstances. This allows for an ambiguity of whether isoforms are functionally distinct. Results: In this study, we analyzed mutants of Drosophila Act79B , the predominant actin expressed in the adult jump muscle. Functional and structural analysis of the Act79B mutants found the flies to have normal jumping ability and sarcomere structure. Analysis of actin gene expression determined that expression of Act88F , an actin gene normally expressed in the flight muscles, was significantly up-regulated in the jump muscles of mutants. This indicated that loss of Act79B caused expansion of Act88F expression. When we created double mutants of Act79B and Act88F , this abolished the jump ability of the flies and resulted in severe defects in myofibril formation. Conclusion: These results indicate that Act88F can functionally substitute for Act79B in the jump muscle, and that the functional compensation in actin expression in the jump muscles only occurs through Act88F . This article is protected by copyright. All rights reserved.
    Electronic ISSN: 1097-0177
    Topics: Medicine
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  • 65
    Publication Date: 2018-01-11
    Description: Plant species are known to adapt locally to their environment, particularly in mountainous areas where conditions can vary drastically over short distances. The climate of such landscapes being largely influenced by topography, using fine-scale models to evaluate environmental heterogeneity may help detecting adaptation to micro-habitats. Here, we applied a multiscale landscape genomic approach to detect evidence of local adaptation in the alpine plant Biscutella laevigata . The two gene pools identified, experiencing limited gene flow along a 1-km ridge, were different in regard to several habitat features derived from a very high resolution (VHR) digital elevation model (DEM). A correlative approach detected signatures of selection along environmental gradients such as altitude, wind exposure, and solar radiation, indicating adaptive pressures likely driven by fine-scale topography. Using a large panel of DEM-derived variables as ecologically relevant proxies, our results highlighted the critical role of spatial resolution. These high-resolution multiscale variables indeed indicate that the robustness of associations between genetic loci and environmental features depends on spatial parameters that are poorly documented. We argue that the scale issue is critical in landscape genomics and that multiscale ecological variables are key to improve our understanding of local adaptation in highly heterogeneous landscapes. Plant species are known to adapt locally to their environment, particularly in mountainous areas where conditions can vary drastically with topography. In this article, we applied a multiscale landscape genomic approach to study local adaptation of the alpine plant Biscutella laevigata using fine-scale digital elevation models (DEMs) as relevant ecological proxies. Our results highlight the relevance of DEM-derived variables and the critical role of spatial resolution to understand local adaptation in alpine landscapes.
    Electronic ISSN: 2045-7758
    Topics: Biology
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  • 66
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    Publication Date: 2018-01-11
    Description: Our inside cover features an immunofluorescence staining of human T cells in contact with lymphoblastoid B cells, which naturally express the IL4I1 enzyme. The B cells were seeded onto polylysine treated glass coverslips before adding allogeneic T cells labeled with a fluorescent dye (red). The conjugates were next permeabilized and labeled with an anti-IL4I1 antibody revealed by a fluorescent secondary antibody (green). In the image, taken from Aubatin et al. (pp. 106–119), IL4I1 granules secreted by B cells into the immune synaptic cleft, induce global T-cell inhibition by decreasing the early signaling events downstream of TCR stimulation.
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  • 67
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    Publication Date: 2018-01-11
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  • 68
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    Publication Date: 2018-01-11
    Print ISSN: 0014-2980
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  • 69
    Publication Date: 2018-01-11
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  • 70
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    Publication Date: 2018-01-11
    Print ISSN: 0014-2980
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  • 71
    Publication Date: 2018-01-11
    Print ISSN: 0014-2980
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  • 72
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    Publication Date: 2018-01-11
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  • 73
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    Publication Date: 2018-01-11
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  • 74
    Publication Date: 2018-01-11
    Description: Background Pancreatic carcinoma is a common cause of cancer deaths worldwide. Biopsy is often required for the initial diagnosis of pancreatic masses. Biopsy can be performed endoscopically or percutaneously with computed tomography (CT) and ultrasound (US) guidance. MRI offers many inherent advantages over CT and US. Purpose/Hypothesis To prospectively evaluate the feasibility, accuracy, and safety of MRI-guided percutaneous coaxial cutting needle biopsy of pancreatic lesions using an open 1.0T high-field MR scanner. Study Type Prospective. Population Thirty-one patients with 31 pancreatic lesions underwent MR-guided percutaneous coaxial cutting needle biopsy. Field Strength/Sequence 1.0T T 2 WI-TSE PDW-aTSE T 1 WI-TFE. Assessment Final diagnosis was confirmed by surgery and clinical follow-up for at least 12 months. The accuracy, sensitivity, and specificity were calculated. Complications were recorded. Statistical Tests There was no statistical analysis in this study. Results The procedure was technically successful and final biopsy samples were adequate for histopathological examination in all patients. Biopsy pathology revealed malignant pancreatic tumor in 25 patients (25/31, 80.6%), and benign pancreatic lesions were present in six patients (6/31, 19.4%). The final diagnosis was pancreatic malignancy in 27 patients and benign disease in four patients, which was confirmed by surgery and clinical follow-up. Two biopsy results were false-negative. The diagnostic accuracy in biopsies was 93.5% (29 of 31). The sensitivity to detect a malignant disease was 92.6% (25 of 27), and the specificity was 100%. All patients tolerated the procedure well; minor peripancreatic hemorrhage was found in two patients after the procedure, and none had major complications either during or after the procedure. Data Conclusion MRI-guided percutaneous biopsy of pancreatic lesions using an open 1.0T high-field scanner has high diagnostic accuracy, which is feasible and safe for use in clinical practice. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 75
    Publication Date: 2018-01-11
    Description: Metaproteomics can greatly assist established high-throughput sequencing methodologies to provide systems biological insights into the alterations of microbial protein functionalities correlated with disease-associated dysbiosis of the intestinal microbiota. Here, we utilized the well-characterized murine T cell transfer model of colitis to find specific changes within the intestinal luminal proteome associated with inflammation. MS proteomic analysis of colonic samples permitted the identification of ∼10,000-12,000 unique peptides that corresponded to 5,610 protein clusters identified across three groups, including the colitic Rag1 −/− T cell recipients, isogenic Rag1 −/− controls, and wild-type mice. We demonstrate that the colitic mice exhibited a significant increase in Proteobacteria and Verrucomicrobia and show that such alterations in the microbial communities contributed to the enrichment of specific proteins with transcription and translation gene ontology terms. In combination with 16S sequencing, our metaproteomics-based microbiome studies provide a foundation for assessing alterations in intestinal luminal protein functionalities in a robust and well-characterized mouse model of colitis, and set the stage for future studies to further explore the functional mechanisms of altered protein functionalities associated with dysbiosis and inflammation. This article is protected by copyright. All rights reserved
    Print ISSN: 1615-9853
    Electronic ISSN: 1615-9861
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 76
    Publication Date: 2018-01-12
    Description: A novel three-dimensional CFD model has been developed on the basis of fluid flow in the shell and lumen sides, and permeation and fouling behavior in the porous membrane zone. The simulated 25-minute dead-end outside-in filtration process showed that the energy consumed by the inlet manifold decreases during the constant pressure filtration. The velocity and pressure distributions in the module change with time. Flux distribution both in the axial and radial directions becomes increasingly more uniform, so does the cake distribution. Flux distribution and cake distribution inter-adjust each other in different modes. A correlation equation has been developed to describe the relationship between the volumetric flow rate and accumulated water production. The correlation equation with simple experiment enables the dynamic evolution of energy consumed by shell inlet manifold to be presented, which can be the criterion of how well the shell inlet manifold or module has been designed. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 77
    Publication Date: 2018-01-12
    Description: Previous experiments observed auto-acceleration in the etherification of glycerol with isobutene. This paper engaged to uncover the reason for this phenomenon via investigating the heterogenicity, including liquid-liquid phase equilibrium and liquid-liquid-solid mass transfer, of the reaction system. Phase behavior analysis showed that the reaction mixture separates into two liquid phases during the whole course of the reaction. The produced mono ethers of glycerol thermodynamically promote the homogenization of the two liquid phases. The modeling results of liquid-liquid-solid mass transfer indicated that the resistance of mass transfer is insignificant during the reaction. The bulk compositions of the two liquid phases are very close to their corresponding equilibrium compositions. An increase of isobutene concentration in the reaction phase is believed to lead all reactions speeding up. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 78
    Publication Date: 2018-01-12
    Description: ABSTRACT This study presents a new approach to investigate the drying behavior and the structure of deposit resulting from drying of solid containing micro droplets. It is shown that deposit structure (porosity and “footprint”) depends on drying conditions. This dependency may contribute to better understanding of particle-forming processes, such as fluidized bed coating. In the framework of this study, sessile droplets containing sodium benzoate dissolved in water were dried on thin glass plates in a small drying chamber. The drying conditions (temperature, moisture content and flow rate of drying gas) and material parameters (solid content of solution) were systematically varied. The drying rate of droplets was determined from the moisture balance of the drying gas. The final 3D shape of dried sessile droplets was measured using white-light interferometry and transformed into a 2D profile using a Monte Carlo method. Moreover the mean porosity of dried droplets was calculated. By comparison of structural information and process conditions it is shown that the drying process may have a large influence on deposit structure. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541
    Electronic ISSN: 1547-5905
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 79
    Publication Date: 2018-01-12
    Description: The liquid film thickness and hydrodynamic entrance length in a vertical tube was studied experimentally and numerically. Measurements using distilled water, 30 wt% MEA and 40 wt% sugar solutions were carried out to investigate the effects of liquid flow rate on the formation of the liquid film. The experimental results validate the new Navier-Stokes based equation in cylindrical coordinates (Eq.16) and the volume of fluid (VOF) model giving a competitively high prediction of the liquid film thickness especially in the low Reynolds number region. In addition, a new empirical model and an improved minimal surface model have been firstly proposed for calculation of the hydrodynamic entrance length, with a relatively reasonable average absolute relative deviation (AARD) of 3.03% and 6.83%, respectively. Furthermore, the effects of the hydrodynamic entry length on the gas-liquid interfacial area calculated by the improved minimal surface model were comprehensively studied, and can be ignored if the ratio of the liquid film length ( y ) and the hydrodynamic entrance length ( λ E ) is lower than 10. However, it should be noted that the hydrodynamic entrance length cannot be ignored in packed columns in which the liquid flow is very complex due to the packings with different structures and materials. This article is protected by copyright. All rights reserved.
    Print ISSN: 0001-1541