Age-related macular degeneration (AMD) is a chronic and progressive inflammatory disease of the retina characterized by photoceptor loss and significant central visual impairment due to either choroidal neovascularization or geographic atrophy. The pathophysiology of AMD is complex and multifactorial, driven by a combination of modifiable and non-modifiable risk factors, molecular mechanisms, and cellular processes that contribute to overall disease onset, severity, and progression. Unfortunately, due to the structural, cellular, and pathophysiologic complexity, therapeutic discovery is challenging.
View Article and Find Full Text PDFMechanisms underlying the SARS-CoV-2-triggered hyperacute thrombo-inflammatory response that causes multi-organ damage in coronavirus disease 2019 (COVID-19) are poorly understood. Several lines of evidence implicate overactivation of complement. To delineate the involvement of complement in COVID-19, we prospectively studied 25 ICU-hospitalized patients for up to 21 days.
View Article and Find Full Text PDFComplement-mediated intravascular hemolysis occurs in canine immune-mediated hemolytic anemia (IMHA). Complement inhibitors might enhance treatment of this disease. Dimers of acetylsalicylic acid such as 5,5'-methylenebis(2-acetoxybenzoic acid) (DAS) have been reported to inhibit complement.
View Article and Find Full Text PDFWe investigate the self-assembly dynamics of an imine-based pentafoil knot and related pentameric circular helicates, each derived from a common bis(formylpyridine)bipyridyl building block, iron(II) chloride, and either monoamines or a diamine. The mixing of circular helicates derived from different amines led to the complete exchange of the N-alkyl residues on the periphery of the metallo-supramolecular scaffolds over 4 days in DMSO at 60 °C. Under similar conditions, deuterium-labeled and nonlabeled building blocks showed full dialdehyde building block exchange over 13 days for open circular helicates but was much slower for the analogous closed-loop pentafoil knot (>60 days).
View Article and Find Full Text PDFA molecular pentafoil knot and doubly and triply entwined [2]catenanes based on circular Fe(II) double helicate scaffolds bind halide anions in their central cavities through electrostatic and CH···X(-) hydrogen-bonding interactions. The binding is up to (3.6 ± 0.
View Article and Find Full Text PDFA [2]rotaxane was produced through the assembly of a picolinaldehyde, an amine, and a bipyridine macrocycle around a Cu(I) template by imine bond formation in close-to-quantitative yield. An analogous [3]rotaxane is obtained in excellent yield by replacing the amine with a diamine, thus showing the suitability of the system for the construction of higher order interlocked structures. The rotaxanes are formed within a few minutes simply through mixing the components in solution at room temperature and they can be isolated through removal of the solvent or precipitation.
View Article and Find Full Text PDFWe report on multicomponent self-sorting to form open circular helicates of different sizes from a primary monoamine, Fe(II) ions, and dialdehyde ligand strands that differ in length and structure by only two oxygen atoms. The corresponding closed circular helicates that are formed from a diamine--a molecular Solomon link and a pentafoil knot--also self-sort, but up to two of the Solomon-link-forming ligand strands can be accommodated within the pentafoil knot structure and are either incorporated or omitted depending on the stage that the components are mixed.
View Article and Find Full Text PDFThis tutorial review outlines the different template strategies that chemists have employed to synthesise knotted molecular topologies. Metal ion coordination, hydrogen bonding and aromatic donor-acceptor interactions have all been used to direct the formation of well-defined crossing points for molecular strands. Advances in the methods used to covalently capture the interwoven structures are highlighted, including the active metal template strategy in which metal ions both organise crossing points and catalyse the bond forming reactions that close the loop to form the topologically complex product.
View Article and Find Full Text PDFMore than a quarter of a century after the first metal template synthesis of a [2]catenane in Strasbourg, there now exists a plethora of strategies available for the construction of mechanically bonded and entwined molecular level structures. Catenanes, rotaxanes, knots and Borromean rings have all been successfully accessed by methods in which metal ions play a pivotal role. Originally metal ions were used solely for their coordination chemistry; acting either to gather and position the building blocks such that subsequent reactions generated the interlocked products or by being an integral part of the rings or "stoppers" of the interlocked assembly.
View Article and Find Full Text PDFWhen alkane thiols and disulfides coadsorb onto gold, they do not necessarily create a mixed monolayer. In particular, when thiols are terminated in groups capable of hydrogen bonding, they can altogether eliminate adsorption of disulfides. Such elimination can be observed directly by using fluorescently labeled disulfides and monitoring their adsorption (or lack of) by fluorescence microscopy.
View Article and Find Full Text PDFSurfaces micropatterned with disjointed cell adhesive/non-adhesive regions allow for precise control of cell shape, internal organization and function. In particular, substrates prepared by the reaction-diffusion ASoMic (nisotropic lid roetching) method localize cells onto transparent micro-islands or tracks surrounded by an opaque, adhesion-resistant background. ASoMic is compatible with several important imaging modalities ( wide-field, fluorescent, TIRF and confocal microscopies), and can be used to study and quantify various intracellular and cellular processes related to cell motility.
View Article and Find Full Text PDFDeformable, spherical aggregates of metal nanoparticles connected by long-chain dithiol ligands self-assemble into nanostructured materials of macroscopic dimensions. These materials are plastic and moldable against arbitrarily shaped masters and can be thermally hardened into polycrystalline metal structures of controllable porosity. In addition, in both plastic and hardened states, the assemblies are electrically conductive and exhibit Ohmic characteristics down to approximately 20 volts per meter.
View Article and Find Full Text PDFDynamic self-assembly (DySA) processes occurring outside of thermodynamic equilibrium underlie many forms of adaptive and intelligent behaviors in natural systems. Relatively little, however, is known about the principles that govern DySA and the ways in which it can be extended to artificial ensembles. This article discusses recent advances in both the theory and the practice of nonequilibrium self-assembly.
View Article and Find Full Text PDFThe NMR spectra of four solutes, used as probes of liquid crystal orientational order, were analyzed. For each solute, samples were prepared at different solute concentrations, and the concentration dependence was used to extrapolate zero-concentration properties. The mean-field (Maier-Saupe) model when applied to solutes neglects solute-solute interactions and assumes all solutes in a mixed-solute sample see the same average environment.
View Article and Find Full Text PDFArrays of surface wrinkles of linearly increasing heights (from tens of nanometers to tens of micrometers) were prepared via a spontaneous reaction-diffusion process based on periodic precipitation. The slopes, dimensions, and positions of the precipitation bands could be controlled precisely by adjusting the concentrations of the participating chemicals as well as the material properties of patterned substrates. Additional control of periodic precipitation by localized UV irradiation allowed for the preparation of discontinuous and curvilinear structures.
View Article and Find Full Text PDFA reaction-diffusion process induced from a micronetwork geometry amplifies changes in the molecular structure of a thin gel film into macroscopic readout patterns. When the gel undergoes a helix-to-coil phase transition, the patterns formed by RD switch from symmetry-broken to symmetric ones. Theoretical analysis explains how the system reconfigures internally in response to mass transfer between the applied network and the probed film.
View Article and Find Full Text PDFHydrogel stamps are used to reactively micropattern various types of substrates. The method, called reactive wet stamping (r-WETS), is general in nature and overcomes several limitations of conventional soft-lithographic techniques. Illustrative applications of r-WETS in surface wettability modification, deposition of metallic microstructures, preparation of supports for electrostatic self-assembly, and multistep reactive patterning are discussed.
View Article and Find Full Text PDFA new experimental technique is described that uses reaction--diffusion phenomena as a means of one-step microfabrication of complex, multilevel surface reliefs. Thin films of dry gelatin doped with potassium hexacyanoferrate are chemically micropatterned with a solution of silver nitrate delivered from an agarose stamp. Precipitation reaction between the two salts causes the surface to deform.
View Article and Find Full Text PDFPhilos Trans A Math Phys Eng Sci
May 2004
This paper begins with a survey of both passive and active microfluidic mixers that have been implemented in recent years. It then describes a micromixing device based on dynamic self-assembly. This device is easy to fabricate and has excellent working characteristics in the continuous-flow mode.
View Article and Find Full Text PDFObjective: To estimate the prevalence of bacterial vaginosis by Nugent Gram stain criteria in a nonclinic national sample of young women entering recruit training; to examine clinical associations with bacterial vaginosis; and to evaluate the performance of a pH test card and Papanicolaou smear against Gram stain as screening tools for bacterial vaginosis.
Methods: A cross-sectional study of 1938 women was conducted. Self-collected vaginal swabs were applied to a colorimetric pH test card and a glass slide for Gram stain evaluation according to the Nugent criteria.