Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

We present the comparative preparation of [Co 7 ( μ 3 -OH) 6 (L) 6 ](ClO 4 ) 2 3 12H 2 O (1), [Co 7 ( μ 3 -CH 3 O) 6 -(L) 6 ](ClO 4 ) 2 (2), and [Co 7 ( μ 3 -N 3 ) 6 (L) 6 ](ClO 4 ) 2 (3), where HL is 2-methoxy-6-[(methylimino)methyl]phenol, using traditional (e.g., 120 °C, 120 h, 23% yield for 1) and microwave-assisted (e.g., 120 °C, 10 min, 46% yield for 1) solvothermal synthesis. The structures contain Co 7 brucite disk [Co 7 ( μ 3 -X) 6 ( μ 2 -O) 6 ] 2þ , where the ligands are arranged in two open hemispheres and the flat inner surface is functionalized when X is OH -, CH 3 O -, and N 3 -. The symmetry of the core decreases in the order 1 > 2 > 3, according to the shape, size, and rigidity of the inner bridges (X). These units are stacked into a chain, and for 1, the water molecules provide a hydrogen-bonded network through the hydroxyl groups. Interestingly, electrospray ionization mass spectrometry (ESI-MS) indicates that the heptacobalt(II) clusters of 1-3 exist in solution and the their compositions in solution are similar to those in the solid. However, the inner ligands μ 3 -CH 3 Oand N 3 are replaced partially with μ 3 -OH -, indicating that μ 3 -OHhas a greater affinity than μ 3 -CH 3 Oor N 3 for Co II , and the parental core of [Co 7 (OH) 6 (L) 6 ] 2þ is the most stable of the three compounds in solution. The presence of edge-sharing octahedra through μ 3 -O or μ 3 -N provides ferromagnetic coupling between nearest neighbors in all cases. Interestingly, for μ 3 -N, it appears to be stronger than μ 3 -O which resulted in single-molecule magnet (SMM) behavior at a higher temperature of 3 K, while they are below the limit of the SQUID magnetometers (2 K) in the case of 1 and 2.

Aerobic photo-oxidation of sulfide into sulfoxide in water is of great interest in green chemistry. In this study, three highly stable Ir­(III)–Zr­(IV) metal–organic frameworks (Ir–Zr MOFs), namely Zr6–Irbpy (bpy is 2,2′-bipyridine), Zr6–IrbpyOMe (bpyOMe is 4,4′-dimethoxy-2,2′-bipyridine), and Zr6–Irphen (phen is 1,10-phenanthroline), are constructed by using [Ir­(pqc)2(L)2]Cl complexes (where pqc is 2-phenylquinoline-4-carboxylic acid and L is an ancillary ligand bpy, bpyOMe, or phen) as linkers and Zr6 cluster as nodes. The constructed Ir–Zr MOFs present high catalytic activity on aerobic photo-oxidation of sulfide into sulfoxide under visible light irradiation in water at room temperature. Moreover, the reaction is high chemoselectivity and functional group tolerance. The catalyst can be readily recycled and reused at least 10 times without loss of catalytic activity. Mechanism studies demonstrate that superoxide radical is the reactive oxygen species in the sulfoxidation, which is generated by electron transfer from the excited triplet photosensitizer 3[Ir–Zr-MOF]* to O2. The high activity of photocatalytic sulfoxidation in water may be attributed to the stabilization of the persulfoxide intermediate by hydrogen bond formation with water solvent, which accelerates the conversion of persulfoxide into sulfoxide and prevents further oxidation of sulfoxide into sulfone. This work provides a new strategy for the green synthesis of sulfoxides under ambient conditions.

Diastereoselective synthesis of bis-cyclometalated Ir(III) stereoisomers Δ/Λ-[Ir(C ∧ N) 2 (D-pro)] and Δ/Λ-[Ir-(C ∧ N) 2 (L-pro)] (where C ∧ N is 2-phenylpyridine (Hppy), (4,6difluorophenyl)pyridine (Hdfppy), and 2-phenylquinoline (Hpq) and pro is proline) with dual stereogenic centers at the metal and auxiliary ligand has been developed. The diastereomers Λ-L and Λ-D, and Δ-L and Δ-D exhibit distinguishable photophysical properties in both solution and the solid state. The thermodynamically stable diastereomers Λ-[Ir(ppy) 2 (L-pro)], Λ-[Ir(dfppy) 2 (Lpro)], and Λ-[Ir(pq) 2 (L-pro)] emit a green emission at 524 nm (Φ = 3.5% and τ = 35 ns), a blue-green emission at 480 nm (Φ = 4.5% and τ = 59 ns), and a red emission at 588 nm (Φ = 6.5% and τ = 200 ns) in DCM solution, respectively, which are blue-shifted accompanied by a large quantum yield and long lifetime relative to the corresponding unstable diastereomers Δ-[Ir(ppy) 2 (L-pro)] at 537 nm (Φ = 2.3% and τ = 29 ns), Δ-[Ir(dfppy) 2 (L-pro)] at 489 nm (Φ = 2.8% and τ = 43 ns), and Δ-[Ir(pq) 2 (L-pro)] at 591 nm (Φ = 5.4% and τ = 192 ns). Similar cases were also observed in crystals, but the signals were significantly red-shifted with respect to those in solution. Single-crystal structural analyses show that the Δ-L and Λ-D diastereomers exhibit larger interligand repulsion and loose molecular packing with respect to the Δ-D and Λ-L diastereomers, resulting in energy and photophysical property differences. In addition, the isomers with Δ and Λ configurations at the metal center exhibit positive and negative circularly polarized luminescence (CPL) signals, respectively, indicating that the effects of the chiral carbon atoms in pro ligands on CPL signals are negligible.

Various types of animal neurons were cultured on a microelectrode array (MEA) platform to form biosensors to detect potential environmental neurotoxins. For a large-scale screening tool, rodent MEA-based cortical-neuron biosensors would be very costly but chick forebrain neurons (FBNs) are abundant, cost-effective, and easy to dissect. However, chick FBNs have a lifespan of ~14 days in vitro and their spontaneous spike activity (SSA) has been difficult to develop and detect. We used a high-density neuron-glia co-culture on an MEA to prolong chick FBN lifetime to 3 months with lifetime-long SSA. A remarkable embryonic age-dependency in the culture's morphology, lifespan, and most features of SSA signal was discovered. Our results show the feasibility of developing a chick FBN-MEA biosensor and also establish a new electrophysiological platform for functional study of an in vitro neuronal network.

Two hexanuclear Co II clusters, NHEt 3 [Co 6 (phendc) 6 ⊃ X] 3 MeOH 3 3H 2 O (X = Cl -(1) or F -(2)), were obtained accidently by the in situ formation of the coordinating ligand H 2 phendc (1,10phenanthroline-2,9-dicarboxylate) from the precursor ligand H 2 phenox (1,10-phenanthroline-2,9dicarbaldehyde dioxime). Halides among the reactants used become the template around which a highly symmetric cluster is generated which display spin-glass magnetic behavior as a consequence of the severe magnetic frustration due to geometrical arrangement of the moments. Different aniontemplate effects were demonstrated by ESI-MS studies. Interestingly, 1 exists in solution; in its solid state, a rare and unique single-crystal to single-crystal transformation is observed upon desolvation, which is accompanied by the departure of NEt 3 . Both dc and ac magnetization data suggest the spinglass behavior for 1 and its guest-free structure H[Co 6 (phendc) 6 Cl] (1 0 ) at different blocking temperatures of 5.3 and 7.8 K, respectively. The absence of this observation for 2 raises an interesting question regarding its origin and provides a remarkable example of fine-tuning of frustrated magnetic properties via host-guest interactions.

The assembly of mixed [1,1′;3′,1′′]terphenyl-4,5′,4′′-tricarboxylic acid (H 3 TPTC) and [1,1′-biphenyl]They are isostructural with hierarchical porosity, consisting of zero-dimensional cage (19.2 Å × 18.9 Å) and one-dimensional pillar channel (29.7 Å × 15.1 Å) in a manner of face sharing. Platon analyses revealed the porous volume ratios are 80.2%, 80.0%, and 77.8% for 1, 1-NH 2 , and for 1-Urea, respectively. Thermogravimetric measurements suggested 53, 51, and 48 wt % guest molecules in 1, 1-NH 2 , and 1-Urea, respectively. 1-NH 2 and 1-Urea were precisely functionalized via the introduction of amino and urea functional groups into the pillar channels. The constructed MOF 1-Urea, incorporating both exposed copper active sites and accessible urea functional groups to substrates, presents high efficiency on catalytic CO 2 cycloaddition with propene oxide to produce cyclic carbonate in the yield of 98% with a TOF value of 136 h −1 at 1 atm and room temperature. This synergic effect provides a new strategy for designing high-efficient catalysts for CO 2 chemical conversion under ambient conditions.

A comparative evaluation of the solvothermal method of synthesis of magnetic Ni(7) discs with four different ligands using the same concentrations of reagents and temperature found microwave heating is more effective than the traditional oven one. Where the former only needs minutes, the latter needs days with an equivalence of 10 min microwave to 1 day of traditional. The size of crystals has a narrow distribution and increases with time for the microwave but is a rather wide distribution for the traditional one. Furthermore the shape of the crystals is more regular for the microwave. The four Ni(7)(II) discs of formulas [Ni(7)L(6)(μ(3)-OMe)(6)](ClO(4))(2) (1-3) and {[Ni(7)(L(4))(6)(μ(3)-OMe)(6)][Ni(L(4))(2)]}(ClO(4))(2) (4) were synthesized as green hexagonal rods from Ni(ClO(4))(2)·6H(2)O in mixed MeOH/MeCN solution and salicylalde Schiff base ligands (L(1) = 2-methoxy-6-(iminomethyl)phenol, L(2) = 2-ethoxy-6-(iminomethyl)phenol, L(3) = 2-methoxy-6-((methylimino)methyl)phenol, L(4) = 2-ethoxy-6-((methylimino)methyl)phenol). X-ray structural analyses show six symmetrically positioned Ni(2) around a central Ni(1) bridged by the μ(3)-methoxide and surrounded by the ligand L which also isolates the discs from one another. The perchlorate sits in the interstices, and the planar [Ni(L(4))(2)] of 4 also inserts itself between the discs. The structures of 1-3 can be regarded as ordered discotic liquid crystals. Electrospray ionization mass spectrometry of solutions showed an exchange of methoxide for hydroxide and a different distribution of [Ni(7)] phase with mixed (MeO/OH) core bridges, confirming a probable "step by step" substitution of MeO(-) by OH(-). Magnetic studies indicate ferromagnetic interaction between Ni(1) and Ni(2) and possible antiferromagnetic between Ni(2) and Ni(2), resulting in a noncollinear system which only reaches half of the moment in 50 kOe at 2 K.