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Spatially resolved and multiplexed MicroRNA quantification from tissue using nanoliter well arrays

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Microsystems & Nanoengineering 2020年第1期6卷 1007-1015页

作者： Maxwell B.Nagarajan Augusto M.Tentori Wen Cai Zhang frank j.slack Patrick S.Doyle Department of Chemical Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA HMS Initiative for RNA Medicine Department of PathologyHarvard Medical SchoolBeth Israel Deaconess Medical CenterBostonMA 02215USA

Spatially resolved gene expression patterns are emerging as a key component of medical studies,including companion diagnostics,but technologies for quantification and multiplexing are *** present a method to perform spatially resolved and multiplexed microRNA(miRNA)measurements from formalin-fixed,paraffin-embedded(FFPE)*** nanoliter well arrays to pixelate the tissue section and photopatterned hydrogels to quantify miRNA,we identified differentially expressed miRNAs in tumors from a genetically engineered mouse model for non-small cell lung cancer(K-ras&(LSL-G12D/+);p53^(fl/fl)).This technology could be used to quantify heterogeneities in tissue samples and lead to informed,biomarker-based diagnostics.

关键词： resolved Spatial lung

Hollow ion atomic structure and X-ray emission in dense hot plasmas

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Matter and Radiation at Extremes 2024年第6期9卷 43-52页

作者： frank B.Rosmej Christopher j.Fontes Sorbonne University Faculty of Science and EngineeringUMR 7605Case 1284 Place JussieuF-75252 ParisFrance Ecole Polytechnique LULIAtomic Physics in Dense PlasmasRoute de SaclayF-91129 PalaiseauFrance Computational Physics Division Los Alamos National LaboratoryLos AlamosNew Mexico 87545USA

Hollow ion X-ray emission is of great interest in high-energy-density research,since negligible opacity allows studies from the interior of very dense *** this paper,ionization potential depressions of the isoelectronic sequences for single and double K-shell vacancies are obtained from a pure ab initio multiconfiguration Hartree-Fock simulation including exact exchange terms and finite temperature dense plasma *** is demonstrated that the simultaneous representation of these ab initio data in the form of a map of hollow ion X-ray transition energies enables identification of important steps in the matter evolution and ionization *** along the isoelectronic sequence as a function of the pumping energy of a X-ray free electron laser also enables visualization of the impact of ionization potential depression on the pathways of hollow ion formation.

关键词： enable interior steps

HIV protease:late action to prevent immune detection

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1408-1409页

作者： Konstantin M.j.Sparrer frank Kirchhoff Institute of Molecular Virology Ulm University Medical CenterUlmGermany

A recent study published in Science by Wang and colleagues shows that premature activation of the HIV-1 protease leads to caspase activation and recruitment domain 8(CARD8)inflammasome-mediated pyroptosis of infected macrophages and CD4+T cells(Fig.1).These findings might help to improve approaches aiming to eliminate the latent viral reservoirs upon HIV-1 *** invading viral pathogens trigger the innate immune system and are usually rapidly controlled and eventually *** sense viral intruders via so-called pattern recognition receptors(PRRs)capable of detecting pathogen-associated molecular patterns(PAMPs)allowing discrimination between self and *** many cases,these patterns are viral nucleic acids that show pathogen-specific structures or emerge at the wrong localization in the ***,activation of PRRs by their respective ligands leads to the induction of various anti-viral signaling cascades,among them the inflammasome.

关键词： eventually action eliminate

Evidence for a Non-β2-Adrenoceptor Binding Site in Human Lung Tissue for a Subset of β2-Adrenoceptor Agonists

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Pharmacology & Pharmacy 2014年第1期5卷 30-36页

作者： Robert j. slack Respiratory TAU Biology GlaxoSmithKline Stevenage UK.

The aim of this study was to compare the binding profile of a range of β2-adrenoceptor (β2-AR) agonists and antagonists in human lung tissue. Radioligand saturation and competition binding experiments were performed by filtration with a β2-AR antagonist ([3H]propranolol) or agonist ([3H]vilanterol) radioligand and membrane fragments generated from lung parenchyma in the presence of 100 μM guanosine 5’-[β,γ-imido]triphosphate (Gpp(NH)p). In membranes prepared from human lung parenchyma, carmoterol, formoterol, ICI118551, propranolol and salbutamol resulted in inhibition of [3H]vilanterol binding to levels that were significantly different from indacaterol, salmeterol and vilanterol (ANOVA, Bonferroni post-test, P 0.05). Indacaterol, salmeterol and vilanterol resulted in full inhibition of [3H]propranolol binding to levels not significantly different from ICI118551 (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol bind to an additional site in human lung parenchyma membranes that is distinct from the β2-AR.

关键词： β2-Adrenoceptor Radioligand Binding Human Lung Tissue Binding Site

Spectro-Microscopy of Living Plant Cells

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Molecular Plant 2012年第1期5卷 14-26页

作者： Klaus Hatter Alfred j. Meixner frank Schleifenbaum Center for Plant Molecular Biology （ZMBP） Plant Physiology and Biophysical Chemistry University of Tubingen Auf der Morgenstelle 1 72076 Tuebingen Germany Institute for Physical and Theoretical Chemistry （IPTC） Nano-Optics University of Tubingen Auf der Morgenstelle 8 72076 Tubingen Germany

Spectro-microscopy, a combination of fluorescence microscopy with spatially resolved spectroscopic techni- ques, provides new and exciting tools for functional cell biology in living organisms. This review focuses on recent devel- opments in spectro-microscopic applications for the investigation of living plant cells in their native tissue context. The application of spectro-microscopic methods led to the recent discovery of a fast signal response pathway for the brassi- nosteroide receptor BRI1 in the plasma membrane of living plant cells. Moreover, the competence of different plant cell types to respond to environmental or endogenous stimuli was determined in vivo by correlation analysis of different optical and spectroscopic readouts such as fluorescence lifetime （FLT）. Furthermore, a new spectro-microscopic technique, fluorescence intensity decay shape analysis microscopy （FIDSAM）, has been developed. FIDSAM is capable of imaging low- expressed fluorophore-tagged proteins at high spatial resolution and precludes the misinterpretation of autofluorescence artifacts. In addition, FIDSAM provides a very effective and sensitive tool on the basis of F6rster resonance energy transfer （FRET） for the qualitative and quantitative determination of protein-protein interaction. Finally, we report on the quan- titative analysis of the photosystem I and II （PSI/PSII） ratio in the chloroplasts of living Arabidopsis plants at room tem- perature, using high-resolution, spatially resolved fluorescence spectroscopy. With this technique, it was not only possible to measure PSI/PSII ratios, but also to demonstrate the differential competence of wild-type and carbohydrate-deficient plants to adapt the PSI/PSII ratio to different light conditions. In summary, the information content of standard microscopic images is extended by several dimensions by the use of spectro-microscopic approaches. Therefore, novel cell physiolog- ical and molecular topics can be addressed and valuable insigh

关键词： Fluorescence microscopy FLIM FRET photosystems protein-protein interaction FIDSAM.

How to identify which patients with asymptomatic carotid stenosis could benefit from endarterectomy or stenting

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Stroke & Vascular Neurology 2018年第2期3卷 92-100页

作者： Kosmas I Paraskevas frank j Veith j David Spence Department of Vascular and Endovascular Surgery Royal Free HospitalLondonUK Department of Vascular Surgery New York University Langone Medical CenterNew YorkUSA Department of Vascular Surgery Cleveland ClinicClevelandOhioUSA Stroke Prevention&Atherosclerosis Research Centre Robarts Research InstituteWestern UniversityLondonCanada

Offering routine carotid endarterectomy(CEA)or carotid artery stenting(CAS)to patients with asymptomatic carotid artery stenosis(ACS)is no longer considered as the optimal management of these *** suboptimal,however,is the policy of offering only best medical treatment(BMT)to all patients with ACS and not considering any of them for prophylactic *** the last few years,there have been many studies aiming to identify reliable predictors of future cerebrovascular events that would allow the identification of patients with high-risk ACS and offer a prophylactic carotid intervention only to these patients to prevent them from becoming *** patients with ACS should receive *** present article will summarise the evidence suggesting ways to identify these high-risk asymptomatic individuals,namely:(1)microemboli detection on transcranial Doppler,(2)plaque echolucency on Duplex ultrasound,(3)progression in the severity of ACS,(4)silent embolic infarcts on brain CT/MRI,(5)reduced cerebrovascular reserve,(6)increased size of juxtaluminal hypoechoic area,(7)identification of intraplaque haemorrhage using MRI and(8)carotid *** evidence suggests that approximately 10%-15%of patents with asymptomatic stenosis might benefit from intervention;this will become more clear after publication of ongoing studies comparing stenting or endarterectomy with best medical *** the meantime,no patient should be offered intervention unless there is evidence of high risk of ipsilateral stroke,from modalities such as those discussed here.

关键词： patients carotid stenosis

Cap snatch prevention:a novel approach to tackle influenza viruses

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Signal Transduction and Targeted Therapy 2023年第6期8卷 2435-2436页

作者： Konstantin M.j.Sparrer frank Kirchhoff Institute of Molecular Virology Ulm University Medical CenterUlmGermany

A recent study published in Science1 by Tsukamoto and colleagues shows that a derivative of tubercidin,a natural product from Streptomyces,selectively inhibits influenza A and B viruses(IAV and IBV,respectively).The compound targets the host RNA methyltransferase MTr1,and thus prevents viral“cap snatching”(Fig.1).These results may help to develop novel drugs that target viral host dependency factors and are thus less likely to induce viral resistance.

关键词： prevention influenza likely

Gas separation using porous cement membrane

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journal of Environmental Sciences 2014年第1期26卷 140-146页

作者： Weiqi Zhang Maria Gaggl Gregor j.G.Gluth frank Behrendt Berlin Institute of Technology Department of Energy Engineering Chair EVUR Chinese Research Academy of Environmental Sciences Berlin Institute of Technology Chair of Building Materials BAM Federal Institute for Materials Research and Testing Division 7.4 Technology of Construction Materials

Gas separation is a key issue in various industrial fields. Hydrogen has the potential for application in clean fuel technologies. Therefore, the separation and purification of hydrogen is an important research subject. CO2 capture and storage have important roles in ＂green chemistry＂. As an effective clean technology, gas separation using inorganic membranes has attracted much attention in the last several decades. Membrane processes have many applications in the field of gas separation. Cement is one type of inorganic material, with the advantages of a lower cost and a longer lifespan. An experimental setup has been created and improved to measure twenty different cement membranes. The purpose of this work was to investigate the influence of gas molecule properties on the material transport and to explore the influence of operating conditions and membrane composition on separation efficiency. The influences of the above parameters are determined, the best conditions and membrane type are found, it is shown that cementitious material has the ability to separate gas mixtures, and the gas transport mechanism is studied.

关键词： gas separation porous membrane clean fuel cement membrane inorganic membranes

From basic properties to the Mott design of correlated delafossites

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npj Computational Materials 2021年第1期7卷 1084-1100页

作者： frank Lechermann European XFEL SchenefeldGermany Center for Computational Quantum Physics Flatiron InstituteNew YorkNYUSA

The natural-heterostructure concept realized in delafossites highlights these layered *** metallic,band-or Mott-insulating character may be associated with individual layers,inter-layer coupling still plays a decisive *** review the correlated electronic structure of PdCoO_(2),PdCrO_(2),and AgCrO_(2),showing that layer-entangled electronic states can deviate from standard classifications of interacting *** finding opens up possibilities for materials design in a subtle Mott-critical *** Hidden-Mott physics,correlation-induced semimetallicity,or Dirac/flat-band dispersions in a Mott background are emerging *** with achievements in the experimental preparation,this inaugurates an exciting research field in the arena of correlated materials.

关键词： materials metallic showing