Filters

2017 - 201930

More filters

2020 - 202330
Reset filters

Settings

End date: 2024 × Start date: 2020 × End date: 2019 × Start date: 2017 × Subject: human ×

Search Results

Now showing 1 - 10 of 30
  • Thumbnail Image
    Item
    High-Sensitivity Rheo-NMR Spectroscopy for Protein Studies
    (Columbus, Ohio : American Chemical Society, 2017) Morimoto, Daichi; Walinda, Erik; Iwakawa, Naoto; Nishizawa, Mayu; Kawata, Yasushi; Yamamoto, Akihiko; Shirakawa, Masahiro; Scheler, Ulrich; Sugase, Kenji
    Shear stress can induce structural deformation of proteins, which might result in aggregate formation. Rheo-NMR spectroscopy has the potential to monitor structural changes in proteins under shear stress at the atomic level; however, existing Rheo-NMR methodologies have insufficient sensitivity to probe protein structure and dynamics. Here we present a simple and versatile approach to Rheo-NMR, which maximizes sensitivity by using a spectrometer equipped with a cryogenic probe. As a result, the sensitivity of the instrument ranks highest among the Rheo-NMR spectrometers reported so far. We demonstrate that the newly developed Rheo-NMR instrument can acquire high-quality relaxation data for a protein under shear stress and can trace structural changes in a protein during fibril formation in real time. The described approach will facilitate rheological studies on protein structural deformation, thereby aiding a physical understanding of shear-induced amyloid fibril formation.
  • Thumbnail Image
    Item
    Liquid-phase electron microscopy of molecular drug response in breast cancer cells reveals irresponsive cell subpopulations related to lack of HER2 homodimers
    (Bethesda, Md. : American Society for Cell Biology, 2017) Peckys, Diana B.; Korf, Ulrike; Wiemann, Stefan; de Jonge, Niels
    The development of drug resistance in cancer poses a major clinical problem. An example is human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer often treated with anti-HER2 antibody therapies, such as trastuzumab. Because drug resistance is rooted mainly in tumor cell heterogeneity, we examined the drug effect in different subpopulations of SKBR3 breast cancer cells and compared the results with those of a drugresistant cell line, HCC1954. Correlative light microscopy and liquid-phase scanning transmission electron microscopy were used to quantitatively analyze HER2 responses upon drug binding, whereby many tens of whole cells were imaged. Trastuzumab was found to selectively cross-link and down-regulate HER2 homodimers from the plasma membranes of bulk cancer cells. In contrast, HER2 resided mainly as monomers in rare subpopulations of resting and cancer stem cells (CSCs), and these monomers were not internalized after drug binding. The HER2 distribution was hardly influenced by trastuzumab for the HCC1954 cells. These findings show that resting cells and CSCs are irresponsive to the drug and thus point toward a molecular explanation behind the origin of drug resistance. This analytical method is broadly applicable to study membrane protein interactions in the intact plasma membrane, while accounting for cell heterogeneity.
  • Thumbnail Image
    Item
    Critical appraisal concerning “Wearable cardioverter defibrillators for the prevention of sudden cardiac arrest: A health technology assessment and patient focus group study”
    (Macclesfield [u.a.] : Dove Medical Press, 2018) Sperzel, Johannes; Staudacher, Ingo; Goeing, Olaf; Stockburger, Martin; Meyer, Thorsten; Oliveira Gonçalves, Ana Sofia; Sydow, Hanna; Schoenfelder, Tonio; Amelung, Volker Eric
    [no abstract available]
  • Thumbnail Image
    Item
    Comments on the authors’ reply to the critical appraisal concerning “Wearable cardioverter defibrillators for the prevention of sudden cardiac arrest: A health technology assessment and patient focus group study”
    (Macclesfield [u.a.] : Dove Medical Press, 2018) Sperzel, Johannes; Staudacher, Ingo; Goeing, Olaf; Stockburger, Martin; Meyer, Thorsten; Oliveira Goncalves, Ana Sofia; Sydow, Hanna; Schoenfelder, Tonio; Amelung, Volker Eric
    [no abstract available]
  • Thumbnail Image
    Item
    Non-touching plasma–liquid interaction – where is aqueous nitric oxide generated?
    (Cambridge : RSC Publ., 2018) Jablonowski, Helena; Schmidt-Bleker, Ansgar; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Wende, Kristian
    Mass transport through graphene is receiving increasing attention due to the potential for molecular sieving. Experimental studies are mostly limited to the translocation of protons, ions, and water molecules, and results for larger molecules through graphene are rare. Here, we perform controlled radical polymerization with surface-anchored self-assembled initiator monolayer in a monomer solution with single-layer graphene separating the initiator from the monomer. We demonstrate that neutral monomers are able to pass through the graphene (via native defects) and increase the graphene defects ratio (Raman ID/IG) from ca. 0.09 to 0.22. The translocations of anionic and cationic monomers through graphene are significantly slower due to chemical interactions of monomers with the graphene defects. Interestingly, if micropatterned initiator-monolayers are used, the translocations of anionic monomers apparently cut the graphene sheet into congruent microscopic structures. The varied interactions between monomers and graphene defects are further investigated by quantum molecular dynamics simulations.
  • Thumbnail Image
    Item
    Effect on healthcare utilization and costs of spinal manual therapy for acute low back pain in routine care: A propensity score matched cohort study
    (San Francisco, California, US : PLOS, 2017) Walker, Jochen; Mertens, Ulf Kai; Schmidt, Carsten Oliver; Chenot, Jean-François
    Spinal manual therapy (SMT) is a popular treatment option for low back pain (LBP). The aim of our analysis was to evaluate the effects of manual therapy delivered by general practitioners and ambulatory orthopedic surgeons in routine care on follow up consultations, sick leave, health service utilization and costs for acute LBP compared to matched patients not receiving manual therapy. This is a propensity score matched cohort study based on health claims data. We identified a total of 113.652 adult patients with acute LBP and no coded red flags of whom 21.021 (18%) received SMT by physicians. In the final analysis 17.965 patients in each group could be matched. Balance on patients' coded characteristics, comorbidity and prior health service utilization was achieved. The provision of SMT for acute LBP had no relevant impact on follow up visits and days of sick leave for LBP in the index billing period and the following year. SMT was associated with a higher proportion of imaging studies for LBP (30.6% vs. 23%, SMD: 0.164 [95% CI 0.143-0.185]). SMT did not lead to meaningful savings by replacing other health services for LBP. SMT for acute non-specific LBP in routine care was not clinically meaningful effective to reduce sick leave and reconsultation rates compared to no SMT and did not lead to meaningful savings by replacing other health services from the perspective of health insurance. This does not imply that SMT is ineffective but might reflect a problem with selection of suitable patients and the quality and quantity of SMT in routine care. National Manual Medicine societies should state clearly that imaging is not routinely needed prior to SMT in patients with low suspicion of presence of red flags and monitor the quality of provided services.
  • Thumbnail Image
    Item
    Graphene oxide functional nanohybrids with magnetic nanoparticles for improved vectorization of doxorubicin to neuroblastoma cells
    (Basel : MDPI AG, 2019) Lerra, L.; Farfalla, A.; Sanz, B.; Cirillo, G.; Vittorio, O.; Voli, F.; Grand, M.L.; Curcio, M.; Nicoletta, F.P.; Dubrovska, A.; Hampel, S.; Iemma, F.; Goya, G.F.
    With the aim to obtain a site-specific doxorubicin (DOX) delivery in neuroblastoma SH-SY5Y cells, we designed an hybrid nanocarrier combining graphene oxide (GO) and magnetic iron oxide nanoparticles (MNPs), acting as core elements, and a curcumin–human serum albumin conjugate as functional coating. The nanohybrid, synthesized by redox reaction between the MNPs@GO system and albumin bioconjugate, consisted of MNPs@GO nanosheets homogeneously coated by the bioconjugate as verified by SEM investigations. Drug release experiments showed a pH-responsive behavior with higher release amounts in acidic (45% at pH 5.0) vs. neutral (28% at pH 7.4) environments. Cell internalization studies proved the presence of nanohybrid inside SH-SY5Y cytoplasm. The improved efficacy obtained in viability assays is given by the synergy of functional coating and MNPs constituting the nanohybrids: while curcumin moieties were able to keep low DOX cytotoxicity levels (at concentrations of 0.44–0.88 µM), the presence of MNPs allowed remote actuation on the nanohybrid by a magnetic field, increasing the dose delivered at the target site.
  • Thumbnail Image
    Item
    Switchable magnetic bulk photovoltaic effect in the two-dimensional magnet CrI3
    (London : Nature Publishing Group, 2019) Zhang, Y.; Holder, T.; Ishizuka, H.; de Juan, F.; Nagaosa, N.; Felser, C.; Yan, B.
    The bulk photovoltaic effect (BPVE) rectifies light into the dc current in a single-phase material and attracts the interest to design high-efficiency solar cells beyond the pn junction paradigm. Because it is a hot electron effect, the BPVE surpasses the thermodynamic Shockley–Queisser limit to generate above-band-gap photovoltage. While the guiding principle for BPVE materials is to break the crystal centrosymmetry, here we propose a magnetic photogalvanic effect (MPGE) that introduces the magnetism as a key ingredient and induces a giant BPVE. The MPGE emerges from the magnetism-induced asymmetry of the carrier velocity in the band structure. We demonstrate the MPGE in a layered magnetic insulator CrI3, with much larger photoconductivity than any previously reported results. The photocurrent can be reversed and switched by controllable magnetic transitions. Our work paves a pathway to search for magnetic photovoltaic materials and to design switchable devices combining magnetic, electronic, and optical functionalities.
  • Thumbnail Image
    Item
    State-of-the-art global models underestimate impacts from climate extremes
    ([London] : Nature Publishing Group UK, 2019) Schewe, Jacob; Gosling, Simon N.; Reyer, Christopher; Zhao, Fang; Ciais, Philippe; Elliott, Joshua; Francois, Louis; Huber, Veronika; Lotze, Heike K.; Seneviratne, Sonia I.; van Vliet, Michelle T. H.; Vautard, Robert; Wada, Yoshihide; Breuer, Lutz; Büchner, Matthias; Carozza, David A.; Chang, Jinfeng; Coll, Marta; Deryng, Delphine; de Wit, Allard; Eddy, Tyler D.; Folberth, Christian; Frieler, Katja; Friend, Andrew D.; Gerten, Dieter; Gudmundsson, Lukas; Hanasaki, Naota; Ito, Akihiko; Khabarov, Nikolay; Kim, Hyungjun; Lawrence, Peter; Morfopoulos, Catherine; Müller, Christoph; Müller Schmied, Hannes; Orth, René; Ostberg, Sebastian; Pokhrel, Yadu; Pugh, Thomas A. M.; Sakurai, Gen; Satoh, Yusuke; Schmid, Erwin; Stacke, Tobias; Steenbeek, Jeroen; Steinkamp, Jörg; Tang, Qiuhong; Tian, Hanqin; Tittensor, Derek P.; Volkholz, Jan; Wang, Xuhui; Warszawski, Lila
    Global impact models represent process-level understanding of how natural and human systems may be affected by climate change. Their projections are used in integrated assessments of climate change. Here we test, for the first time, systematically across many important systems, how well such impact models capture the impacts of extreme climate conditions. Using the 2003 European heat wave and drought as a historical analogue for comparable events in the future, we find that a majority of models underestimate the extremeness of impacts in important sectors such as agriculture, terrestrial ecosystems, and heat-related human mortality, while impacts on water resources and hydropower are overestimated in some river basins; and the spread across models is often large. This has important implications for economic assessments of climate change impacts that rely on these models. It also means that societal risks from future extreme events may be greater than previously thought.
  • Thumbnail Image
    Item
    Environmental co-benefits and adverse side-effects of alternative power sector decarbonization strategies
    ([London] : Nature Publishing Group UK, 2019) Luderer, Gunnar; Pehl, Michaja; Arvesen, Anders; Gibon, Thomas; Bodirsky, Benjamin L.; de Boer, Harmen Sytze; Fricko, Oliver; Hejazi, Mohamad; Humpenöder, Florian; Iyer, Gokul; Mima, Silvana; Mouratiadou, Ioanna; Pietzcker, Robert C.; Popp, Alexander; van den Berg, Maarten; van Vuuren, Detlef; Hertwich, Edgar G.
    A rapid and deep decarbonization of power supply worldwide is required to limit global warming to well below 2 °C. Beyond greenhouse gas emissions, the power sector is also responsible for numerous other environmental impacts. Here we combine scenarios from integrated assessment models with a forward-looking life-cycle assessment to explore how alternative technology choices in power sector decarbonization pathways compare in terms of non-climate environmental impacts at the system level. While all decarbonization pathways yield major environmental co-benefits, we find that the scale of co-benefits as well as profiles of adverse side-effects depend strongly on technology choice. Mitigation scenarios focusing on wind and solar power are more effective in reducing human health impacts compared to those with low renewable energy, while inducing a more pronounced shift away from fossil and toward mineral resource depletion. Conversely, non-climate ecosystem damages are highly uncertain but tend to increase, chiefly due to land requirements for bioenergy.