Free-standing, interconnected metallic nanowire networks with densities as low as 40 mg/cm
have been achieved over centimeter-scale areas, using electrodeposition into polycarbonate membranes that ...have been ion-tracked at multiple angles. Networks of interconnected magnetic nanowires further provide an exciting platform to explore 3-dimensional nanomagnetism, where their structure, topology, and frustration may be used as additional degrees of freedom to tailor the materials properties. New magnetization reversal mechanisms in cobalt networks are captured by the first-order reversal curve method, which demonstrate the evolution from strong demagnetizing dipolar interactions to intersection-mediated domain wall pinning and propagation, and eventually to shape-anisotropy dominated magnetization reversal. These findings open up new possibilities for 3-dimensional integrated magnetic devices for memory, complex computation, and neuromorphics.
Free-standing, interconnected metallic nanowire networks with densities as low as 40 mg/cm3 have been achieved over centimeter-scale areas, using electrodeposition into polycarbonate membranes that ...have been ion-tracked at multiple angles. Networks of interconnected magnetic nanowires further provide an exciting platform to explore 3-dimensional nanomagnetism, where their structure, topology, and frustration may be used as additional degrees of freedom to tailor the materials properties. New magnetization reversal mechanisms in cobalt networks are captured by the first-order reversal curve method, which demonstrate the evolution from strong demagnetizing dipolar interactions to intersection-mediated domain wall pinning and propagation, and eventually to shape-anisotropy dominated magnetization reversal. These findings open up new possibilities for 3-dimensional integrated magnetic devices for memory, complex computation, and neuromorphics.
The relative yields of Υ mesons produced in p + p and Pb+Pb collisions at √s NN = 5.02 TeV and reconstructed via the dimuon decay channel are measured using data col- lected by the CMS experiment. ...Double ratios are formed by comparing the yields of the excited states, Υ(2S) and Υ(3S), to the ground state, Υ(1S), in both Pb+Pb and p + p collisions at the same energy. The double ratios, Υ(nS)/Υ(1S) PbPb /Υ(nS)/Υ(1S) pp , are measured to be 0.308 ± 0.055 (stat) ± 0.019 (syst) for the Υ(2S) and less than 0.26 at 95% confidence level for the Υ(3S). The double ratios are studied as a function of col- lision centrality, as well as dimuon transverse momentum, and rapidity. As a function of collision centrality the Υ(2S) double ratio is consistent with unity in the most peripheral (70–100%) bin and is consistent with zero in the most central (0–5%) bin. The Υ(2S) double ratio is consistent with a constant dependence on the kinematic variables, with a large suppression seen throughout the studied kinematic range. No significant Υ(3S) signal is found in the Pb+Pb data. The Υ(3S) double ratio is consistently below unity for all bins, including the most peripheral (50–100%) bin, indicating a strong suppression of the Υ(3S) relative to the Υ(1S).
Free-standing, interconnected metallic nanowire networks with density as low as 40 mg/cm^{3} have been achieved over cm-scale areas, using electrodeposition into polycarbonate membranes that have ...been ion-tracked at multiple angles. Networks of interconnected magnetic nanowires further provide an exciting platform to explore 3-dimensional nanomagnetism, where their structure, topology and frustration may be used as additional degrees of freedom to tailor the materials properties. New magnetization reversal mechanisms in cobalt networks are captured by the first-order reversal curve method, which demonstrate the evolution from strong demagnetizing dipolar interactions to intersections-mediated domain wall pinning and propagation, and eventually to shape-anisotropy dominated magnetization reversal. These findings open up new possibilities for 3-dimensional integrated magnetic devices for memory, complex computation, and neuromorphics.
A biomimetic, ion-regulated molecular receptor was synthesized via the Weak-Link Approach (WLA). This structure features both a calix4arene moiety which serves as a molecular recognition unit and an ...activity regulator composed of hemilabile phosphine alkyl thioether ligands (P,S) chelated to a Pt(II) center. The host–guest properties of the ion-regulated receptor were found to be highly dependent upon the coordination of the Pt(II) center, which is controlled through the reversible coordination of small molecule effectors. The environment at the regulatory site dictates the charge and the structural conformation of the entire assembly resulting in three accessible binding configurations: one closed, inactive state and two open, active states. One of the active states, the semiopen state, recognizes a neutral guest molecule, while the other, the fully open state, recognizes a cationic guest molecule. Job plots and 1H NMR spectroscopy titrations were used to study the formation of these inclusion complexes, the receptor binding modes, and the receptor binding affinities (K a) in solution. Single crystal X-ray diffraction studies provided insight into the solid-state structures of the receptor when complexed with each guest molecule. The dipole moments and electrostatic potential maps of the structures were generated via DFT calculations at the B97D/LANL2DZ level of theory. Finally, we describe the reversible capture and release of guests by switching the receptor between the closed and semiopen configurations via elemental anion and small molecule effectors.
A Redox-Switchable, Allosteric Coordination Complex Cheng, Ho Fung; d’Aquino, Andrea I; Barroso-Flores, Joaquín ...
Journal of the American Chemical Society,
11/2018, Letnik:
140, Številka:
44
Journal Article
Recenzirano
A redox-regulated molecular tweezer complex was synthesized via the weak-link approach. The PtII complex features a redox-switchable hemilabile ligand (RHL) functionalized with a ferrocenyl moiety, ...whose oxidation state modulates the opening of a specific coordination site. Allosteric regulation by redox agents gives reversible access to two distinct structural statesa fully closed state and a semi-open statewhose interconversion was studied via multinuclear NMR spectroscopy, cyclic voltammetry, and UV–vis–NIR spectroscopy. Two structures in this four-state system were further characterized via SCXRD, while the others were modeled through DFT calculations. This fully reversible, RHL-based system defines an unusual level of electrochemical control over the occupancy of a specific coordination site, thereby providing access to four distinct coordination states within a single system, each defined and differentiated by structure and oxidation state.
Aberrant expression of microRNAs (miRNAs) and the enzymes that control their processing have been reported in multiple biological processes including primary and metastatic tumours, but the ...mechanisms governing this are not clearly understood. Here we show that TAp63, a p53 family member, suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR-130b to suppress metastasis. Metastatic mouse and human tumours deficient in TAp63 express Dicer at very low levels, and we found that modulation of expression of Dicer and miR-130b markedly affected the metastatic potential of cells lacking TAp63. TAp63 binds to and transactivates the Dicer promoter, demonstrating direct transcriptional regulation of Dicer by TAp63. These data provide a novel understanding of the roles of TAp63 in tumour and metastasis suppression through the coordinate transcriptional regulation of Dicer and miR-130b and may have implications for the many processes regulated by miRNAs.
Small noncoding miRNAs represent underexplored targets of genomic aberrations and emerging therapeutic targets. The 3q26.2 amplicon is among the most frequent genomic aberrations in multiple cancer ...lineages including ovarian and breast cancers. We demonstrate that hsa-miR-569 (hereafter designated as miR569), which is overexpressed in a subset of ovarian and breast cancers, at least in part due to the 3q26.2 amplicon, alters cell survival and proliferation. Downregulation of TP53INP1 expression by miR569 is required for the effects of miR569 on survival and proliferation. Targeting miR569 sensitizes ovarian and breast cancer cells overexpressing miR569 to cisplatin by increasing cell death both in vitro and in vivo. Thus targeting miR569 could potentially benefit patients with the 3q26.2 amplicon and subsequent miR569 elevation.
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•3q26.2 copy number amplification is associated with increased miR569 levels•miR569 enhances tumor growth and metastasis•miR569 alters expression of TP53INP1 independent of transcriptional regulation•anti-miR569 induces cell death and sensitizes cancer cells to cisplatin
Chaluvally-Raghavan et al. show that the expression of miR569 is increased in ovarian and breast cancers with 3q26.2 amplification, which is common across human cancers, and that miR569 reduces the expression of TP53INP1 in cancer cells to confer increased proliferation and cisplain-resistance.
Metastatic cancer is extremely difficult to treat, and the presence of metastases greatly reduces a cancer patient's likelihood of long-term survival. The ZEB1 transcriptional repressor promotes ...metastasis through downregulation of microRNAs (miRs) that are strong inducers of epithelial differentiation and inhibitors of stem cell factors. Given that each miR can target multiple genes with diverse functions, we posited that the prometastatic network controlled by ZEB1 extends beyond these processes. We tested this hypothesis using a mouse model of human lung adenocarcinoma metastasis driven by ZEB1, human lung carcinoma cells, and human breast carcinoma cells. Transcriptional profiling studies revealed that ZEB1 controls the expression of numerous oncogenic and tumor-suppressive miRs, including miR-34a. Ectopic expression of miR-34a decreased tumor cell invasion and metastasis, inhibited the formation of promigratory cytoskeletal structures, suppressed activation of the RHO GTPase family, and regulated a gene expression signature enriched in cytoskeletal functions and predictive of outcome in human lung adenocarcinomas. We identified several miR-34a target genes, including Arhgap1, which encodes a RHO GTPase activating protein that was required for tumor cell invasion. These findings demonstrate that ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression and provide a compelling rationale to develop miR-34a as a therapeutic agent in lung cancer patients.
Macrocycles capable of host–guest chemistry are an important class of structures that have attracted considerable attention because of their utility in chemical separations, analyte sensing, signal ...amplification, and drug delivery. The deliberate design and synthesis of such structures are rate-limiting steps in utilizing them for such applications, and coordination-driven supramolecular chemistry has emerged as a promising tool for rapidly making large classes of such systems with attractive molecular recognition capabilities and, in certain cases, catalytic properties. A particularly promising subset of such systems are stimuli-responsive constructs made from hemilabile ligands via the weak-link approach (WLA) to supramolecular coordination chemistry. Such structures can be reversibly toggled between different shapes, sizes, and charges based upon small-molecule and elemental-anion chemical effectors. In doing so, one can deliberately change their recognition properties and both stoichiometric and catalytic chemistries, thereby providing mimics of allosteric enzymes. The vast majority of structures made to date involve two-state systems, with a select few being able to access three different states. Herein, we describe the synthesis of a new allosterically regulated four-state macrocycle assembled via the WLA. The target structure was made via the stepwise assembly of ditopic bidentate hemilabile N-heterocyclic carbene thioether (NHC,S) and phosphino thioether (P,S) ligands at PtII metal nodes. The relatively simple macrocycle displays complex dynamic behavior when addressed with small-molecule effectors, and structural switching can be achieved with several distinct molecular cues. Importantly, each state was fully characterized by multinuclear NMR spectroscopy and, in some cases, single-crystal X-ray diffraction studies and density functional theory computational models. This new structure opens the door to complex multicue switching reminiscent of multistate chemoswitches that could be important in controlling stoichiometric and catalytic transformations as well as generating molecular logic systems.
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