A mild and efficient palladium-catalyzed cyanation of aryl chlorides with K4[Fe(CN)6

An efficient palladium-catalyzed cyanation of aryl chlorides is established. In the presence of a highly effective Pd/CM-phos catalyst, cyanation of aryl chlorides proceeds at 70 °C in general, which is the mildest reaction temperature achieved so far for this process. Common functional groups such as keto, aldehyde, ester, nitrile and -NH(2), and heterocyclic coupling partners including N-H indoles are well tolerated. Moreover, a sterically hindered nonactivated ortho,ortho-disubstituted electrophile is shown to be a feasible coupling partner in cyanation.     

Internal Lewis acid assisted hydrogen bond donor catalysis

Boronate ureas are introduced as a new class of noncovalent catalysts for conjugate addition reactions with enhanced activity. Through intramolecular coordination of the urea functionality to a strategically placed Lewis acid, rate enhancements up to 10 times that of more conventional urea catalysts are observed. The tunable nature of boronate ureas is a particularly attractive feature and enables the rational design of catalysts for optimal performance, in terms of both activity and stereocontrol, in new bond-forming processes.     

Deterministic approximation algorithms for sphere constrained homogeneous polynomial optimization problems

Due to their fundamental nature and numerous applications, sphere constrained polynomial optimization problems have received a lot of attention lately. In this paper, we consider three such problems: (i) maximizing a homogeneous polynomial over the sphere; (ii) maximizing a multilinear form over a Cartesian product of spheres; and (iii) maximizing a multiquadratic form over a Cartesian product of spheres. Since these problems are generally intractable, our focus is on designing polynomial-time approximation algorithms for them. By reducing the above problems to that of determining the L ₂-diameters of certain convex bodies, we show that they can all be approximated to within a factor of Ω((log n/n) ^d/2–1) deterministically, where n is the number of variables and d is the degree of the polynomial. This improves upon the currently best known approximation bound of Ω((1/n) ^d/2–1) in the literature. We believe that our approach will find further applications in the design of approximation algorithms for polynomial optimization problems with provable guarantees.     

Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis

Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 × 10-7). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 × 10-5). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 × 10-10). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA.     

AGR2, a mucinous ovarian cancer marker, promotes cell proliferation and migration

Ovarian cancer is a leading cause of death in women. Early detection of ovarian cancer is essential to decrease mortality. However, the early diagnosis of ovarian cancer is difficult due to a lack of clinical symptoms and suitable molecular diagnostic markers. Thus, identification of meaningful tumor biomarkers with potential clinical application is clearly needed. To search for a biomarker for the early detection of ovarian cancer, we identified human anterior gradient 2 (AGR2) from our systematic analysis of paired normal and ovarian tumor tissue cDNA microarray. We noted a marked overexpression of AGR2 mRNA and protein in early stage mucinous ovarian tumors compared to normal ovarian tissues and serous type ovarian tumors by Western blot analysis and immunohistochemistry. To further elucidate the role of AGR2 in ovarian tumorigenesis, stable 2774 human ovarian cancer cell lines overexpressing AGR2 were established. Forced expression of AGR2 in 2774 cells enhanced the growth and migration of ovarian cancer cells. AGR2 protein was detected in the serum of mucinous ovarian cancer patients by Western blot and ELISA analysis. Thus, AGR2 is a potential biomarker for the diagnosis of mucinous ovarian cancer and an ELISA assay may facilitate the early detection of mucinous ovarian cancer using patient serum.     

A novel pH-responsive polysaccharidic ionic complex for proapoptotic D-(KLAKLAK)2 peptide delivery

We report charge-switching ionic nanocomplexes comprised of glycol chitosan grafted with 2,3-dimethylmaleic acid (DMA) (denoted as 'GCS-g-DMA' hereafter) and a proapoptotic peptide. This system allowed for improved peptide delivery to tumor sites via a mechanism of selective peptide release when the pH was dropped from 7.4 to 6.8.     

Efficient and stable panchromatic squaraine dyes for dye-sensitized solar cells

A new series of stable, unsymmetrical squaraine near-IR sensitizers (JK-216 and JK-217), which are assembled using both thiophenyl pyrrolyl and indolium groups, exhibit a panchromatic light harvesting up to 780 nm. The JK-216 based cell exhibited a record efficiency of 6.29% for near-IR DSSCs. In addition, the JK-217 device showed an excellent stability under a light soaking test at 60 °C for 1000 h.     

A versatile palladium catalyst system for Suzuki-Miyaura coupling of alkenyl tosylates and mesylates

A general and effective palladium system for Suzuki-Miyaura coupling of alkenyl electrophiles under mild reaction conditions is reported. With the Pd(OAc)(2)/CM-phos system, a variety of alkenyl tosylates are coupled well with ArB(OH)(2). Moreover, the first successful examples of using alkenyl mesylates in alkenylation are also described.