A Quad-Band and Polarization-Insensitive Metamaterial Absorber with a Low Profile Based on Graphene-Assembled Film.

A quad-band metamaterial absorber using a periodically arranged surface structure placed on an ultra-thin substrate is demonstrated in this paper. Its surface structure consists of a rectangular patch and four L-shaped structures distributed symmetrically. The surface structure is able to have strong electromagnetic interactions with incident microwaves, thereby generating four absorption peaks at different frequencies. With the aid of the near-field distributions and impedance matching analysis of the four absorption peaks, the physical mechanism of the quad-band absorption is revealed. The usage of graphene-assembled film (GAF) provides further optimization to increase the four absorption peaks and promotes the low-profile characteristic. In addition, the proposed design has good tolerance to the incident angle in vertical polarization. The proposed absorber in this paper has the potential for filtering, detection, imaging, and other communication applications.

N-Heterocyclic Carbene/Magnesium Cocatalyzed Radical Relay Assembly of Aliphatic Keto Nitriles.

An unprecedented N-heterocyclic carbene and magnesium cocatalyzed three-component acylcyanoalkylation of alkenes with cycloketone oxime esters and aldehydes is presented. This method displayed good scope generality, providing a transition-metal- and photoredox-free pathway to access various multifunctionalized aliphatic keto nitrile structures under mild reaction conditions. Moreover, this strategy is supposed to follow a radical relay mechanism via a single electron transfer event of a Mg/matched Breslow intermediate/oxime ester electron-donating acceptor (EDA) complex.

Application of isatin-derived saturated esters in the synthesis of 3,3'-spirooxindole γ-butyrolactams.

Stable while reactive isatin-derived saturated esters have been utilized as 3-carbon synthons in a base-promoted formal [3 + 2] annulation with N-Boc imines. The developed protocol offers a direct pathway for the rapid and divergent construction of two classes of 3,3'-spirooxindole γ-butyrolactam skeletons that are recognized as the privileged structures of various bioactive compounds. This protocol also has the advantages of mild reaction conditions, scalability and wide reaction scope.

Asymmetric Synthesis of C2-Quaternary Indolin-3-ones Enabled by N-Heterocyclic Carbene Catalysis.

An N-heterocyclic carbene (NHC)-catalyzed formal [4 + 2] annulation of 2-aryl-3 H-indol-3-ones with α,ß-unsaturated carboxylic acids bearing γ-H was developed via an in situ activation strategy. The reaction involves the γ-addition of vinyl enolates to the unique cyclic ketimines to afford chiral tricyclic indolin-3-ones with a quaternary carbon center at 2-position. This protocol provides a rapid and enantioselective pathway to access a novel class of structurally important C2-quaternary indolin-3-ones that might be useful for drug discovery.

Orally bioavailable and brain-penetrant pyridazine and pyridine-derived γ-secretase modulators reduced amyloidogenic Aß peptides in vivo.

Accumulation of amyloid ß (Aß) in brain is a pathological hallmark of Alzheimer's disease (AD). Aß is generated after sequential cleavage of its parental molecule, amyloid precursor protein (APP), by ß- and γ-secretases. Inhibition of γ-secretase activity is an effective approach for the reduction of Aß levels. Since γ-secretase targets many different substrates, selective inhibition of its cleavage of APP is believed to be critical in order to avoid undesirable side effects. γ-Secretase modulator (GSM) shifts the cleavage site on APP and production of amyloidogenic to non-amyloidogenic Aß fragments. Since GSMs only modulate and do not block cleavage of γ-secretase substrates, they are believed less likely to produce untoward adverse reactions. Here, we report in vivo Aß-lowering profiles of a pyridazine and a pyridine-derived GSM: GSM-C (Wan et al., 2011a) and GSM-D (Wan et al., 2011b). Both compounds reduced Aß40 and Aß42 productions, increased shorter Aß fragments, and had little effect on Notch signaling (∼100-fold selective). They had excellent oral bioavailability (97.8% for GSM-C, ∼100% for GSM-D) and good brain permeability (free brain to free blood AUC ratio of 0.41 and 1.10 for GSM-C and GSM-D, respectively). Oral administration of these compounds in both acute and sub-chronic conditions reduced Aß levels in plasma and brain in rats in a dose- and time-dependent manner. Therefore, GSM-C and GSM-D represent two GSMs that are orally bioavailable and brain-permeable. They could serve as excellent tools in the investigation of the role of Aß peptides in AD pathogenesis.

Γ-secretase modulators do not induce Aß-rebound and accumulation of ß-C-terminal fragment.

γ-secretase inhibitors (GSIs) have been developed to reduce amyloid-ß (Aß) production for the treatment of Alzheimer's disease by inhibiting the cleavage of amyloid precursor protein (APP). However, cross-inhibitory activity on the processing of Notch can cause adverse reactions. To avoid these undesirable effects, γ-secretase modulators (GSMs) are being developed to selectively reduce toxic Aß production without perturbing Notch signaling. As it is also known that GSIs can cause a paradoxical increase of plasma Aß over the baseline after a transient reduction (known as Aß-rebound), we asked if GSMs would cause a similar rebound and what the potential mechanism might be. Our studies were performed with one GSI (LY-450139) and two chemically distinct GSMs. Although LY-450139 caused Aß-rebound as expected in rat plasma, the two GSMs did not. Inhibition of APP processing by LY-450139 induced an accumulation of γ-secretase substrates, α- and ß-C-terminal fragments of APP, but neither GSM caused such an accumulation. In conclusion, we discover that GSMs, unlike GSIs, do not cause Aß-rebound, possibly because of the lack of accumulation of ß-C-terminal fragments. GSMs may be superior to GSIs in the treatment of Alzheimer's disease not only by sparing Notch signaling but also by avoiding Aß-rebound.

Confirmation of PSORS psoriasis susceptibility loci in a Chinese population.

We investigated 38 Chinese psoriasis families with 19 reported microsatellite markers. Families comprised a total of 96 affected and 92 unaffected individuals. Genotyping results were analyzed using parametric and nonparametric linkage analysis. Our results confirmed the published linkage with the PSORS1 locus, as well as the PSORS2 locus, which has not been previously shown in the Chinese population. Significant two-point LOD scores were obtained in a parametric linkage analysis with markers D6S1610 and D17S944. Nonparametric linkage values greater than 1.6 ( P<0.05) were obtained with markers D6S1610, D17S944 and D17S785.

[Searching for the susceptibility loci of psoriasis in Chinese].

OBJECTIVE: To search for the susceptibility genes of patients with psoriasis in Chinese. METHODS: 38 psoriasis families were determined to search for the susceptibility loci by selecting 19 reported polymorphic microsatellite DNA markers and making use of fluorescein-labeled PCR with Mega BACE sequencer. RESULTS: The significant two-point Lod score values of parametric linkage analysis were obtained with D6S1610 marker (1.18 at theta; = 0.2) and D17S944 marker (1.60 at theta; = 0.1); the NPL values greater than 1.6 (P < 0.05) of non-parametric analysis were obtained with D6S1610 marker, D17S944 marker and D17S785 marker. CONCLUSION: A putative linkage to D6S1610 marker, D17S944 marker and D17S785 marker.