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991.
Jakub Hrubý Vinicius T. Santana Dmytro Kostiuk Martin Bou
ek Samuel Lenz Michal Kern Peter iffalovi
Joris van Slageren Petr Neugebauer 《RSC advances》2019,9(42):24066
The scalability and stability of molecular qubits deposited on surfaces is a crucial step for incorporating them into upcoming electronic devices. Herein, we report on the preparation and characterisation of a molecular quantum bit, copper(ii)dibenzoylmethane [Cu(dbm)2], deposited by a modified Langmuir–Schaefer (LS) technique onto a graphene-based substrate. A double LS deposition was used for the preparation of a few-layer-graphene (FLG) on a Si/SiO2 substrate with subsequent deposition of the molecules. Magnetic properties were probed by high-frequency electron spin resonance (HF-ESR) spectroscopy and found maintained after deposition. Additional spectroscopic and imaging techniques, such as Raman spectroscopy (RS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and scanning electron microscopy (SEM) were performed to characterise the deposited sample. Our approach demonstrated the possibility to utilise a controlled wet-chemistry protocol to prepare an array of potential quantum bits on a disordered graphene-based substrate. The deployed spectroscopic techniques showed unambiguously the robustness of our studied system with a potential to fabricate large-scale, intact, and stable quantum bits.Graphene-based hybrid material with array of copper(ii)-based quantum bits was prepared by a wet-chemistry protocol and characterised by HF-ESR, XPS, Raman, and AFM. 相似文献
992.
Sotonte Ebenibo Chimaroke EdeogaJim Wan Samuel Dagogo-Jack 《Metabolism: clinical and experimental》2014
Objective
A hemoglobin (Hb) A1c range of 5.7%–6.4% has been recommended for the diagnosis of prediabetes. To determine the significance of such “prediabetic” HbA1c levels, we compared glucoregulatory function in persons with HbA1c levels of 5.7%–6.4% and those with HbA1c < 5.7%.Methods
We studied 280 nondiabetic adults (142 black, 138 white; mean (± SD) age 44.2 ± 10.6 years). Each subject underwent clinical assessment, blood sampling for HbA1c measurement, and a 75-g oral glucose tolerance test at baseline. Additional assessments during subsequent outpatient visits included insulin sensitivity, using homeostasis model assessment (HOMA)-IR and the hyperinsulinemic euglycemic clamp; insulin secretion, using HOMA-B and frequently samples intravenous glucose tolerance test (FSIVGTT) and disposition index (DI); and measurement of fat mass, using DXA.Results
Compared to subjects with HbA1c < 5.7%, persons with HbA1c levels of 5.7%–6.4% were older, and had higher body mass index (BMI) and insulin secretion but similar insulin sensitivity. When the two groups were matched in age and BMI, persons with HbA1c 5.7%–6.4% were indistinguishable from those with HbA1c < 5.7% with regard to all measures of glycemia and glucoregulatory function.Conclusions
Unlike glucose-defined prediabetes status, an HbA1c range of 5.7%–6.4% does not reliably identify individuals with impaired insulin action or secretion, the classical defects underlying the pathophysiology of prediabetes. Thus, HbA1c cannot validly replace blood glucose measurement in the diagnosis of prediabetes. If utilized as a screening test due to convenience, aberrant HbA1c values should be corroborated with blood glucose measurement before therapeutic intervention. 相似文献993.
Joanne M. Hildebrand Maria C. Tanzer Isabelle S. Lucet Samuel N. Young Sukhdeep K. Spall Pooja Sharma Catia Pierotti Jean-Marc Garnier Renwick C. J. Dobson Andrew I. Webb Anne Tripaydonis Jeffrey J. Babon Mark D. Mulcair Martin J. Scanlon Warren S. Alexander Andrew F. Wilks Peter E. Czabotar Guillaume Lessene James M. Murphy John Silke 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(42):15072-15077
Necroptosis is considered to be complementary to the classical caspase-dependent programmed cell death pathway, apoptosis. The pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) is an essential effector protein in the necroptotic cell death pathway downstream of the protein kinase Receptor Interacting Protein Kinase-3 (RIPK3). How MLKL causes cell death is unclear, however RIPK3–mediated phosphorylation of the activation loop in MLKL trips a molecular switch to induce necroptotic cell death. Here, we show that the MLKL pseudokinase domain acts as a latch to restrain the N-terminal four-helix bundle (4HB) domain and that unleashing this domain results in formation of a high-molecular-weight, membrane-localized complex and cell death. Using alanine-scanning mutagenesis, we identified two clusters of residues on opposing faces of the 4HB domain that were required for the 4HB domain to kill cells. The integrity of one cluster was essential for membrane localization, whereas MLKL mutations in the other cluster did not prevent membrane translocation but prevented killing; this demonstrates that membrane localization is necessary, but insufficient, to induce cell death. Finally, we identified a small molecule that binds the nucleotide binding site within the MLKL pseudokinase domain and retards MLKL translocation to membranes, thereby preventing necroptosis. This inhibitor provides a novel tool to investigate necroptosis and demonstrates the feasibility of using small molecules to target the nucleotide binding site of pseudokinases to modulate signal transduction.Programmed necrosis or “necroptosis” has emerged in the past 5 years as a cell death mechanism that complements the conventional cell death pathway, apoptosis, in multicellular organisms. In contrast to apoptosis, necroptosis does not appear to serve an important role in multicellular organism development (1–3) but participates in the defense against pathogens and is a likely culprit in destructive inflammatory conditions (4–7). Receptor Interacting Protein Kinase-3 (RIPK3) was identified as a key effector of necroptosis in 2009 (4, 5) and its substrate, the pseudokinase Mixed Lineage Kinase Domain-Like (MLKL), in 2012 (8, 9), but the molecular events following RIPK3-mediated phosphorylation of MLKL required to induce cell death are unclear. The RIPK1/RIPK3/MLKL necrosome has been proposed to activate PGAM5 (phosphoglycerate mutase 5) and Drp1 (Dynamin-related protein 1) to cause mitochondrial fragmentation and cell death (10), but the requirement for PGAM5, Drp1, and mitochondria for necroptosis has been questioned (1, 11–13).We described the structure of mouse MLKL revealing that MLKL contains a C-terminal pseudokinase domain and an N-terminal four-helix bundle (4HB) domain connected by a two-helix linker (the “brace” helices) (1). Based on our mutational and biochemical analyses, we proposed that the catalytically inactive pseudokinase domain functions as a molecular switch and that RIPK3-mediated phosphorylation triggers this switch by inducing a conformational change in MLKL (1, 14).Recently it has been proposed that the 4HB domain is the death effector domain within MLKL and that the killing function of MLKL relies on its oligomerization and plasma membrane association (15–18). The stoichiometry of the oligomer is, however, contentious and has been reported to contain three (15), four (16), and possibly six (17) MLKL protomers. Furthermore, several mechanisms for how this oligomer causes cell death have been proposed: Cai et al. proposed it activates the calcium channel protein Tprm7 and promotes calcium influx (15), Chen et al. showed it increased sodium influx (16), and Wang et al. proposed that the oligomerized form of MLKL has the ability to bind negatively charged lipids, including phosphoinositides and cardiolipin, which facilitates its disruption of membrane integrity (17), a model supported by a subsequent paper (18).Here, we show that the MLKL 4HB domain is sufficient to induce necroptosis and identify several charged residues clustered on two faces that are required for this function. Surprisingly the polarity of several of these charged residues is not conserved between mouse and human MLKL, and alanine substitution of negatively charged residues on the α4 helix of the 4HB domain disrupted function. This finding challenges the importance of phospholipid binding to the killing activity of the 4HB domain and illustrates that membrane association cannot solely be attributed to the interaction of poorly conserved basic residues within the MLKL 4HB domain. Intriguingly, mutation of a second cluster of residues on the 4HB domain did not preclude membrane localization or oligomerization but did prevent cell death, illustrating that additional function(s) beyond membrane translocation are required for the 4HB domain to induce cell death. MLKL oligomerization and membrane translocation were also inhibited by a small molecule, compound 1, which we identified on the basis of its affinity for the nucleotide binding site of the MLKL pseudokinase domain. These data support a model for MLKL function whereby the pseudokinase domain of MLKL holds the 4HB domain in check until phosphorylated by RIPK3, which causes a conformational change in the pseudokinase domain to unleash the 4HB domain to oligomerize and associate with membranes. Activation of MLKL can be thwarted by a small MLKL binding molecule, indicating the feasibility of targeting the nucleotide binding or “pseudoactive” sites of pseudokinases, a hitherto unexplored class of therapeutic targets. 相似文献
994.
Samuel Obamiyi Zhihui Wang Edward Sommers P. Emile Rossouw Dimitrios Michelogiannakis 《The Angle orthodontist》2019,89(6):897
Objectives:To examine normal Overbite Depth Indicator (ODI) and Anteroposterior Dysplasia Indicator (APDI) values in African Americans and to compare them with mean values from white patients. Secondary aims were to compare mean ODI and APDI values among different age, gender, and combined age-gender groups in African American patients.Materials and Methods:Lateral cephalometric radiographs of 160 African American patients (97 boys and 63 girls; age, 7 to 14 years) with normal occlusion and no history of orthodontic treatment were collected from the Bolton-Brush Growth Center. Cephalometric images were hand traced, and ODI and APDI values were assessed. Two-sample t tests were used to compare mean ODI and APDI values between African American and white patients; and between male and female African American patients. One-way analysis of variance, followed by the Tukey test, was used to compare mean ODI and APDI values among different African American age and combined age-gender groups.Results:Mean ODI and APDI values were significantly lower (P < .0001) in African American than white patients with normal occlusion and no history of orthodontic treatment. Mean ODI and APDI values increased with age in African American patients, and there were no significant gender differences.Conclusions:The mean ODI and APDI values in 7- to 14-year-old African Americans with normal occlusion and no history of orthodontic treatment were 70.9° and 78.1°, respectively, and were significantly lower than the mean values for white patients in the same age range. 相似文献
995.
Bani Tamraz Lori Reisner Audrey L. French Samuel T. King Margaret A. Fischl Igho Ofotokun Angela Kashuba Joel Milam Kerry Murphy Michael Augenbraun Chenglong Liu Patrick R. Finley Bradley Aouizerat Jennifer Cocohoba Stephen Gange Peter Bacchetti Ruth M. Greenblatt 《Pharmacotherapy》2019,39(9):899-911
996.
Steven D. Townsend Audrey G. Ross Kai Liu Samuel J. Danishefsky 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(22):7931-7935
Highly concise and stereospecific routes to cis and trans fusion, carrying various functionality at one of the bridgehead carbons, have been accomplished.Our group has been studying the synthetic utility of the Diels–Alder (DA) reaction of the parent cyclobutenone, 2 (1). Recently reported results demonstrate that 2 is a highly reactive, endo-selective dienophile (Fig. 1, Eq. 1) (2). We have also developed a series of intramolecular Diels–Alder (IMDA) reactions, wherein the cyclobutenone component is tethered to various conjugated dienes (compare 4); cycloaddition of these substrates delivers adducts of the type 5, which can be readily converted to trans-fused systems bearing iso-DA patterns (Fig. 1, Eq. 2, 5→6) (3). Additionally, we have described the synthesis and DA cycloaddition of an even more powerful dienophile, 2-bromocyclobutenone (Fig. 1, Eq. 3, 7) (4). The direct adducts of this [4+2] reaction (compare 8) are readily converted to norcarane carboxylic acids (9) through exposure to hydroxide base. The research described herein was initially focused on efforts to add carbon-based nucleophiles to DA cycloadducts of the type 8. It might well have been expected that such reactions would give rise to products such as 10, wherein a ketone is appended to the junction of the norcarane system (Fig. 1, Eq. 4).Open in a separate windowFig. 1.Expanding the scope of the Diels–Alder reaction. 相似文献
997.
Jack P. Hughes Felipe D. Blanco Craig E. Banks Samuel J. Rowley-Neale 《RSC advances》2019,9(43):25003
A screen-printable ink that contained varying percentage mass incorporations of two dimensional tungsten disulphide (2D-WS2) was produced and utilized to fabricate bespoke printed electrodes (2D-WS2-SPEs). These WS2-SPEs were then rigorously tested towards the Hydrogen Evolution Reaction (HER) within an acidic media. The mass incorporation of 2D-WS2 into the 2D-WS2-SPEs was found to critically affect the observed HER catalysis with the larger mass incorporations resulting in more beneficial catalysis. The optimal (largest possible mass of 2D-WS2 incorporation) was the 2D-WS2-SPE40%, which displayed a HER onset potential, Tafel slope value and Turn over Frequency (ToF) of −214 mV (vs. RHE), 51.1 mV dec−1 and 2.20 , respectively. These values significantly exceeded the HER catalysis of a bare/unmodified SPE, which had a HER onset and Tafel slope value of −459 mV (vs. RHE) and 118 mV dec−1, respectively. Clearly, indicating a strong electrocatalytic response from the 2D-WS2-SPEs. An investigation of the signal stability of the 2D-WS2-SPEs was conducted by performing 1000 repeat cyclic voltammograms (CVs) using a 2D-WS2-SPE10% as a representative example. The 2D-WS2-SPE10% displayed remarkable stability with no variance in the HER onset potential of ca. −268 mV (vs. RHE) and a 44.4% increase in the achievable current over the duration of the 1000 CVs. The technique utilized to fabricate these 2D-WS2-SPEs can be implemented for a plethora of different materials in order to produce large numbers of uniform and highly reproducible electrodes with bespoke electrochemical signal outputs.Two dimensional tungsten disulphide screen-printed electrodes display efficient electrocatalysis towards the hydrogen evolution reaction. 相似文献
998.
Samuel Saire-Saire Eduardo C. M. Barbosa Daniel Garcia Leandro H. Andrade Sergi Garcia-Segura Pedro H. C. Camargo Hugo Alarcon 《RSC advances》2019,9(38):22116
Gold nanoparticles (Au NPs) have been widely employed in catalysis. Here, we report on the synthesis and catalytic evaluation of a hybrid material composed of Au NPs deposited at the surface of magnetic cobalt ferrite (CoFe2O4). Our reported approach enabled the synthesis of well-defined Au/CoFe2O4 NPs. The Au NPs were uniformly deposited at the surface of the support, displayed spherical shape, and were monodisperse in size. Their catalytic performance was investigated towards the reduction of 4-nitrophenol and the selective oxidation of dimethylphenylsilane to dimethylphenylsilanol. The material was active towards both transformations. In addition, the LSPR excitation in Au NPs could be employed to enhance the catalytic performance, which was demonstrated in the 4-nitrophenol reduction. Finally, the magnetic support allowed for the easy recovery and reuse of the Au/CoFe2O4 NPs. In this case, our data showed that no significant loss of performance took place even after 10 reaction cycles in the oxidation of dimethylphenylsilane to dimethylphenylsilanol. Overall, our results indicate that Au/CoFe2O4 are interesting systems for catalytic applications merging high performances, recovery and re-use, and enhancement of activities under solar light illumination.We present a cleaner chemical synthesis process of a magnetic recoverable Au/CoFe2O4 hybrid nanocomposite catalyst that has remarkable activity in catalytic reduction and oxidation, improved by surface plasmon resonance. 相似文献
999.
Cho Soo Hyun Choe Yeong Sim Kim Hee Jin Jang Hyemin Kim Yeshin Kim Si Eun Kim Seung Joo Kim Jun Pyo Jung Young Hee Kim Byeong C. Baker Suzanne L. Lockhart Samuel N. Na Duk L. Park Seongbeom Seo Sang Won 《European journal of nuclear medicine and molecular imaging》2020,47(8):1938-1948
European Journal of Nuclear Medicine and Molecular Imaging - We developed a new method to directly calculate Centiloid (CL) units of 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) without... 相似文献
1000.
Weitz Jeffrey I. Haas Sylvia Ageno Walter Goldhaber Samuel Z. Turpie Alexander G. G. Goto Shinya Angchaisuksiri Pantep Nielsen Jørn Dalsgaard Kayani Gloria Farjat Alfredo E. Schellong Sebastian Bounameaux Henri Mantovani Lorenzo G. Prandoni Paolo Kakkar Ajay K. 《Journal of thrombosis and thrombolysis》2020,50(2):267-277
Journal of Thrombosis and Thrombolysis - Venous thromboembolism (VTE) is common in cancer patients and is an important cause of morbidity and mortality. The Global Anticoagulant Registry in the... 相似文献