A Chemical Inhibitor of the Skp2/p300 Interaction that Promotes p53‐Mediated Apoptosis

Skp2 is thought to have two critical roles in tumorigenesis. As part of the SCF^Skp2 ubiquitin ligase, Skp2 drives the cell cycle by mediating the degradation of cell cycle proteins. Besides the proteolytic activity, Skp2 also blocks p53‐mediated apoptosis by outcompeting p53 for binding p300. Herein, we exploit the Skp2/p300 interaction as a new target for Skp2 inhibition. An affinity‐based high‐throughput screen of a combinatorial cyclic peptoid library identified an inhibitor that binds to Skp2 and interferes with the Skp2/p300 interaction. We show that antagonism of the Skp2/p300 interaction by the inhibitor leads to p300‐mediated p53 acetylation, resulting in p53‐mediated apoptosis in cancer cells, without affecting Skp2 proteolytic activity. Our results suggest that inhibition of the Skp2/p300 interaction has a great potential as a new anticancer strategy, and our Skp2 inhibitor can be developed as a chemical probe to delineate Skp2 non‐proteolytic function in tumorigenesis.     

An intrinsic synthesis parameter governing the crystallization of silico(zinco)aluminophosphate molecular sieves

One of the most fundamental but yet unanswered questions in the synthesis of zeolites and zeolite-like materials is whether or not any parameter controlling the microporosity of the crystallized product from synthesis mixtures with feasible chemical compositions exists. Here we report that an experimentally optimized parameter (ca. 3.3 ≤ MOH/P₂O₅ ≤ 5.3, where M is alkali metal ions) is the criterion bringing about the successful formation of various high-charge-density silicoaluminophosphate (SAPO) and zincoaluminophosphate (ZnAPO) molecular sieves, without the aid of organic structure-directing agents. The materials obtained using this empirical concept include SAPO molecular sieves with CHA and LTA topologies, as well as a SAPO FAU/EMT intergrowth, and ZnAPO ones with CZP and SOD topologies. This study demonstrates the existence of an essential factor determining not only phase selectivity but also microporosity (0.3–2 nm) in the synthesis of zeotypes with charged frameworks which may offer interesting opportunities for more efficiently producing novel zeolite structures and/or compositions.

The existence of an essential parameter (ca. 3.3 ≤ MOH/P₂O₅ ≤ 5.3, where M is alkali metal ions used as structure-directing agents) determining phase selectivity and microporosity in the synthesis of zeotypes with charged frameworks is demonstrated.     

A simple and cost-effective molecular diagnostic system and DNA probes synthesized by light emitting diode photolithography

This work introduces a novel chip to be used in the future as a simple and cost-effective method for creating DNA arrays using light emission diode (LED) photolithography. The DNA chip platform contains 24 independent reaction sites, which allows for the testing of a corresponding amount of patients’ samples in hospital. An array of commercial UV LEDs and lens systems was combined with a microfluidic flow system to provide patterning of 24 individual reaction sites, each with 64 independent probes. Using the LED array instead of conventional laser exposure systems or micro-mirror systems significantly reduces the cost of equipment. The microfluidic system together with microfluidic flow cells drastically reduces the amount of used reagents, which is important due to the high cost of commercial reagents. The DNA synthesis efficiency was verified by fluorescence labeling and conventional hybridization.     

Novel fabrication route for carbon-free and dense CuInSe2 (CIS) thin films via a non-vacuum process for solar cell application

Carbon-free CuInSe₂ (CIS) thin film with a dense microstructure has been prepared using a novel non-vacuum based fabrication route. Cu_xS_y and In₂Se₃ binary nanoparticles, approximately 10 nm in size, were synthesized by a low temperature colloidal process. The precursor film was deposited using the coating ink formulated with the binary nanoparticles and pyridine, and then annealed in the rapid thermal annealing (RTA) chamber at 540 °C for 15 min under selenium (Se) atmosphere. Scanning electron micrographs, X-ray diffraction patterns and Raman spectra showed a phase pure carbon-free and dense CIS thin film was prepared in this method. A solar cell device fabricated using this CIS thin film showed the following photovoltaic characteristics: V_OC = 350 mV, J_SC = 24.72 mA cm⁻², FF = 38.73% and η = 3.36% under standard AM 1.5 condition.     

Comment on “Quantum Signature Scheme with Weak Arbitrator”

This comment explains that the quantum signature scheme proposed by Ming-Xing Luo et al. (in Int. J. Theor. Phys. 51:2134, 2012) cannot satisfy the signature requirements. The comment presents methods of possible attacks by forgers, while also demonstrating that it is difficult to proceed by the normal protocol because of some errors in the formula of the scheme.     

Misalignment tolerance analysis and fabrication for highly efficient parallel optical-electrical convertor module

A compact, highly efficient, and passively assembled parallel optical-electrical convertor module (POECM) for active optical cable application is proposed. This paper presents our POECM structure, optical design simulation results, fabrication process, and data transmission test results, in sequence. The POECM has a compact size of \(18.5\hbox {mm} \times 10\hbox {mm} \times 2.8\hbox {mm}\) . We confirm a data rate of total throughput at 21.6 Gbps ( \(5.4\hbox {Gbps} \times 4\) channels) with a bit error rate of less than \(10^{-12}\) .     

New device architecture of a thermoelectric energy conversion for recovering low-quality heat

Low-quality heat is generally discarded for economic reasons; a low-cost energy conversion device considering price per watt, $/W, is required to recover this waste heat. Thin-film based thermoelectric devices could be a superior alternative for this purpose, based on their low material consumption; however, power generated in conventional thermoelectric device architecture is negligible due to the small temperature drop across the thin film. To overcome this challenge, we propose new device architecture, and demonstrate approximately 60 Kelvin temperature differences using a thick polymer nanocomposite. The temperature differences were achieved by separating the thermal path from the electrical path; whereas in conventional device architecture, both electrical charges and thermal energy share same path. We also applied this device to harvest body heat and confirmed its usability as an energy conversion device for recovering low-quality heat.     

Bilaminar pattern of tibial condyle cartilage layer on the fat-suppressed 3D gradient echo images: artifact or structural and biochemical difference in composition of cartilage?

The purpose of this study was to examine if an unusual bilaminar pattern of lateral tibial condyle cartilage layer on the fat-suppressed three-dimensional (3D) spoiled gradient echo sequence is artifactual or correlates with structural and/or biochemical composition of cartilage. The laminar appearance of the lateral tibial condyle cartilage layer was studied on fat-suppressed 3D spoiled gradient echo MR images of the knee joint in 67 patients (mean age: 28y) performed at 1.0 Tesla. After i.v. administration of gadopentetate dimeglumine, diffusion of the contrast media into cartilage layer was qualitatively analysed over time on inversion recovery spin echo images of knee joints of five asymptomatic volunteers (mean age: 25y). In a patient with osteosarcoma and total knee replacement, MR examination of cartilage layer of lateral tibial plateau was compared with histologic specimens stained with Safranin-O, demonstrating proteoglycan distribution in cartilage. The retrospective analysis of 67 knee joints revealed a bilaminar appearance of lateral tibial condyle cartilage layer in the gradient echo images in the majority of cases (81%) with a statistically significant tendency to a trilaminar pattern in patients older than 20 years. With i.v. contrast administration, the contrast enhancement was only observed in the superficial zone of tibial cartilage layer. Histologic specimens in one patient demonstrated a good correlation between thickness of proteoglycan-free and proteoglycan-rich laminae of lateral tibial condyle on Safranin-O staining with hyperintense and hypointense zones, respectively, on corresponding fat-suppressed 3D spoiled gradient echo images (correlation coefficient of 0.87). Bilaminar pattern of tibial condyle cartilage layer on fat-suppressed 3D spoiled gradient echo images in younger subjects is not an artifact or an intrachondral lesion, but it may represent a regional difference in composition of extracellular cartilage matrix possibly produced by a highly-oriented collagen fiber structure associated with a high concentration of proteoglycans in the middle and deep portion of the cartilage layer.     

Reversible interpenetration in a metal-organic framework triggered by ligand removal and addition

Caging cages: Crystals of a metal-organic framework, MOF-123 [Zn(7) O(2) (NBD)(5) (DMF)(2) ] have a three-dimensional porous structure in which DMF ligands (see picture, pink) protrude into small channels. Removal of these ligands triggers the transformation of this MOF to the doubly interpenetrating form, MOF-246 [Zn(7) O(2) (NBD)(5) ]. Moreover, addition of DMF into MOF-246 triggers reverse transformation to give MOF-123. NBD=2-nitrobenzene-1,4-dicarboxylate.     

Synthesis and Characterization of Cationic Glycidyl-Based Poly(aminoester)-Folic Acid Targeting Conjugates and Study on Gene Delivery

A new poly(aminoester) (EPAE-FA) containing folic acid and amino groups in the backbone and side chain was synthesized. EPAE-FA self-assembled readily with the plasmid DNA (pCMV-βgal) in HEPES buffer and was characterized by dynamic light scattering, zeta potential, fluorescence images, and XTT cell viability assays. To evaluate the transfection effect of graft ratio of FA on the EPAE system, EPAE-FA polymers with two different graft ratios (EPAE-FA12k and EPAE-FA14k) were also prepared. This study found that all EPAE-FA polymers were able to bind plasmid DNA and yielded positively charged complexes with nano-sized particles ( < 200 nm). To assess the transfection efficiency mediated by EPAE and EPAE-FA polymers, we performed in vitro transfection activity assays using FR-negative (COS-7) and FR-positive (HeLa) cells. The EPAE-FA12k/DNA and EPAE-FA14k/DNA complexes were able to transfect HeLa cell in vitro with higher transfection efficiency than PEI25k/DNA at the similar weight ratio. These results demonstrated that the introduction of FA into EPAE system had a significant effect on transferring ability for FR-positive cells (HeLa). Examination of the cytotoxicity of PEI25k and EPAE-FA system revealed that EPAE-FA system had lower cytotoxicity. In this paper, EPAE-FA seemed to be a novel cationic poly(aminoester) for gene delivery and an interesting candidate for further study.