Unusual Electro‐Optic Kerr Response in a Self‐Stabilized Amorphous Blue Phase with Nanoscale Smectic Clusters

We investigated the electro‐optic response in the “foggy” amorphous blue phase (BPIII) as well as in the isotropic phase. To the best of our knowledge, such a study has not yet been performed due to the very limited thermal range of BPIII. In this study, we used a single‐component chiral bent‐core liquid crystal with a self‐stabilized BPIII, which is stable over a wide temperature range. The results show that the response time is on the order of hundreds of microseconds in the isotropic phase and increases to 1–2 ms in the BPIII (at T_I?BP–T <1), then drastically increases up to a few tens of milliseconds upon further cooling in BPIII. Such an unusual behavior was explained on the basis of the high rotational viscosity and/or the existence of nanoscale smectic (Sm) clusters. The Kerr constant was also measured and found to be ～500 pm V^?2, which is the largest among bent‐core BP systems reported so far and comparable with that of polymer‐stabilized BPs.     

Oriented immobilization of periodateoxidized monoclonal antibodies on amino and hydrazide derivatives of eupergit C

Amino and hydrazyno derivatives of Eupergit C were prepared by reaction of the beads with hexamethylene diamine (HMD) and adipic acid dihydrazide (ADH), respectively. Monoclonal antibodies (mAbs) against carboxypeptidase A (CPA) and horse radish peroxidase (HRP) were prepared, and those that did not inhibit the respective enzymatic activities were selected. The carbohydrate moieties of these antibodies were oxidized by reaction with sodium periodate and then coupled onto the modified beads. The oxidation and coupling reactions were optimized to achieve highly active matrix-conjugated antibodies. Thus, antibody-matrix conjugates that possessed antigen-binding activities close to the theoretical value of 2 mol antigen bound/mol immobilized antibody were obtained.     

Novel water-soluble bacteriochlorophyll derivatives for vascular-targeted photodynamic therapy: synthesis, solubility, phototoxicity and the effect of serum proteins

New negatively charged water-soluble bacteriochlorophyll (Bchl) derivatives were developed in our laboratory for vascular-targeted photodynamic therapy (VTP). Here we focused on the synthesis, characterization and interaction of the new candidates with serum proteins and particularly on the effect of serum albumin on the photocytotoxicity of WST11, a representative compound of the new derivatives. Using several approaches, we found that aminolysis of the isocyclic ring with negatively charged residues markedly increases the hydrophilicity of the Bchl sensitizers, decreases their self-association constant and selectively increases their affinity to serum albumin, compared with other serum proteins. The photocytotoxicity of the new candidates in endothelial cell culture largely depends on the concentration of the serum albumin. Importantly, after incubation with physiological concentrations of serum albumin (500-600 microM), WST11 was found to be poorly photocytotoxic (>80% endothelial cell survival in cell cultures). However, in a recent publication (Mazor, O. et al. [2005] Photochem. Photobiol. 81, 342-351) we showed that VTP of M2R melanoma xenografts with a similar WST11 concentration resulted in approximately 100% tumor flattening and >70% cure rate. We therefore propose that the two studies collectively suggest that the antitumor activity of WST11 and probably of other similar candidates does not depend on direct photointoxication of individual endothelial cells but on the vascular tissue response to the VTP insult.     

Application of Fluorescent Nanocrystals (q-dots) for the Detection of Pathogenic Bacteria by Flow-Cytometry

Fluorescent semiconductor nanocrystals (q-dots) benefit from practical features such as high fluorescence intensity, broad excitation band and emission diameter dependency. These unique spectroscopic characterizations make q-dots excellent candidates for new fluorescent labels in multi-chromatic analysis, such as Flow-Cytometry (FCM). In this work we shall present new possibilities of multi-labeling and multiplex analysis of pathogenic bacteria, by Flow-Cytometry (FCM) analysis and new specific IgG—q-dots conjugates. We have prepared specific conjugates against B. anthracis spores (q-dots585-IgGαB. anthracis and q-dots655-IgGαB.anthracis). These conjugates enabled us to achieve double staining of B. anthracis spores which improve the FCM analysis specificity versus control Bacillus spores. Moreover, multiplexed analysis of B. anthracis spores and Y. pestis bacteria was achieved by using specific antibodies labeled with different q-dots to obtain: q-dots585-IgGαB. anthracis and q-dots655-IgGαY.pestis, each characterized by its own emission peak as a marker. Specific and sensitive multiplex analysis for both pathogens has been achieved, down to 10³ bacteria per ml in the sample.     

Synthesis of orthogonally protected optically pure ketopiperazine, diketopiperazine, ketodiazepane, and 3-aminopyrrolidone building blocks for peptidomimetic combinatorial chemistry

A simple and convenient synthesis of orthogonally protected multi-tethered, optically pure 2-ketopiperazine, diketopiperazine, 2-ketodiazepane and 3-aminopyrrolidone scaffolds for Fmoc combinatorial chemistry has been developed. It utilizes accessible chiral amino acid precursors, sequentially applying reductive alkylation, dipeptide coupling and regioselective ring formation as key steps. These scaffolds are expansion of our ‘pool of privileged building blocks’ and can introduce valuable drug-like properties in three independent directions to any medicinally relevant piperazine-, diazepane- and pyrrolidone-based motif by ‘around-the-scaffold’ drug optimization. The synthetic routes reported in this work are general and applicable for the preparation of a diverse library of scaffolds, controlling chirality, arm position and length as well as the nature of functional moieties at the arms for further diversification in three independent directions. In addition, these building blocks have a wide application scope in managing fast and efficient multi-cyclic optimization processes in the combinatorial chemistry and drug design fields.     

Localized In Vivo Activation of a Photoactivatable Doxorubicin Prodrug in Deep Tumor Tissue

Sparing sensitive healthy tissue from chemotherapy exposure is a critical challenge in the treatment of cancer. The work described here demonstrates the localized in vivo photoactivation of a new chemotherapy prodrug of doxorubicin (DOX). The DOX prodrug (DOX‐PCB) was 200 times less toxic than DOX and was designed to release pure DOX when exposed to 365 nm light. This wavelength was chosen because it had good tissue penetration through a 1 cm diameter tumor, but had very low skin penetration, due to melanin absorption, preventing uncontrolled activation from outside sources. The light was delivered specifically to the tumor tissue using a specialized fiber‐optic LED system. Pharmacokinetic studies showed that DOX‐PCB had an α circulation half‐life of 10 min which was comparable to that of DOX at 20 min. DOX‐PCB demonstrated resistance to metabolic cleavage ensuring that exposure to 365 nm light was the main mode of in vivo activation. Tissue extractions from tumors exposed to 365 nm light in vivo showed the presence of DOX‐PCB as well as activated DOX. The exposed tumors had six times more DOX concentration than nearby unexposed control tumors. This in vivo proof of concept demonstrates the first preferential activation of a photocleavable prodrug in deep tumor tissue.     

AdS 5 Solutions of Type IIB Supergravity and Generalized Complex Geometry

We use the formalism of generalized geometry to study the generic supersymmetric AdS ₅ solutions of type IIB supergravity that are dual to ${\mathcal{N}=1}We use the formalism of generalized geometry to study the generic supersymmetric AdS ₅ solutions of type IIB supergravity that are dual to N=1{\mathcal{N}=1} superconformal field theories (SCFTs) in d = 4. Such solutions have an associated six-dimensional generalized complex cone geometry that is an extension of Calabi-Yau cone geometry. We identify generalized vector fields dual to the dilatation and R-symmetry of the dual SCFT and show that they are generalized holomorphic on the cone. We carry out a generalized reduction of the cone to a transverse four-dimensional space and show that this is also a generalized complex geometry, which is an extension of K?hler-Einstein geometry. Remarkably, provided the five-form flux is non-vanishing, the cone is symplectic. The symplectic structure can be used to obtain Duistermaat-Heckman type integrals for the central charge of the dual SCFT and the conformal dimensions of operators dual to BPS wrapped D3-branes. We illustrate these results using the Pilch-Warner solution.     

Rapid Homogenous Time-Resolved Fluorescence (HTRF) Immunoassay for Anthrax Detection

Infection with Bacillus anthracsis spores induces an acute anthrax disease that can cause casualties and death in untreated cases. Thus rapid diagnosis of anthrax at early stage of the disease is essential to allow an effective treatment. Here we present the development of rapid and sensitive homogenous time-resolved fluorescence (HTRF) immunoassays based on the energy transfer process of europium cryptate (EuK) donor to AlexaFluor647 acceptor. The energy transfer process is limited to d?<?10 nm, making the HTRF an ideal assay for examination of homogenous and complex samples, since only mutual binding of the donor and acceptor antibodies to the analyte would result in positive signal. HTRF assay was developed for the detection of the bacterial Protective Antigen (PA) toxin, a serological marker that correlates with bacteremia in infected hosts, using two monoclonal anti-PA antibodies that specifically recognize two different epitopes on the PA molecule. The assay was sensitive enabling detection of 2 ng/ml PA in the serum of B. anthracsis-infected rabbits in only 15 min assay. Additionally, HTRF assay was developed for the detection of bacterial spores using polyclonal anti-spore antibodies that recognize many epitopes on the bacterial surface. The assay enabled the detection of 2?×?10⁶ spores/ml in 30 min assay and was specific, showing no cross reactivity with closely related non-virulent bacillus cereus strain. This study describes the use of the HTRF assay for the detection of both singled-epitope (proteins) and multi-epitope (particles) as rapid, simple and sensitive method that can be used at the time that fast results are needed to allow an effective medical care.     

Engineering of new crosslinked near‐infrared fluorescent polyethylene glycol bisphosphonate nanoparticles for bone targeting

Bisphosphonates (BPs) are nonhydrolysable pyrophosphate analogs with high affinity to hydroxyapatite (HAP, bone mineral) and are mainly used for treatment of various bone diseases. In this study, we designed and prepared crosslinked BP nanoparticles by dispersion copolymerization of three monomers: methacrylate PEG bisphosphonate, N‐(3‐aminopropyl) methacrylamide, and tetra(ethylene glycol) diacrylate. The size and size distribution of these PEG‐BP nanoparticles were controlled by changing various polymerization parameters. These BP particles possess dual functionality: covalent attachment of a dye (e.g., near IR fluorescent dye) or drug to the nanoparticles through the primary amine groups belonging to the aminopropyl methacrylamide monomeric units and chelation to the bone mineral HAP through the BP groups belonging to the methacrylate PEG bisphosphonate monomeric units, for enhanced long term bone‐targeted imaging and therapy applications. Body distribution of the optimal crosslinked BP nanoparticles was tested on a chicken embryo model via intravenous administration. This study indicated that the fluorescence intensity of the all organs (e.g., blood, spleen, liver, kidney, and heart) except the bones decreased significantly within 48 h (p < 0.05) while that of the bones hardly changed over that time (p > 0.05). © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4282–4291     

MAX CUT in cubic graphs

We present an improved semidefinite programming based approximation algorithm for the MAX CUT problem in graphs of maximum degree at most 3. The approximation ratio of the new algorithm is at least 0.9326. This improves, and also somewhat simplifies, a result of Feige, Karpinski and Langberg. We also observe that results of Hopkins and Staton and of Bondy and Locke yield a simple combinatorial 4/5-approximation algorithm for the problem. Finally, we present a combinatorial 22/27-approximation algorithm for the MAX CUT problem for regular cubic graphs.