Redaporfin Development for Photodynamic Therapy and its Combination with Glycolysis Inhibitors†

Photodynamic therapy (PDT) remains an underutilized treatment modality in oncology. Many efforts have been dedicated to the development of better photosensitizers, better formulations and delivery methods, rigorous planning of light dose distribution in tissues, mechanistic insight, improvement of treatment protocols and combinations with other therapeutic agents. Hopefully, progress in all these fields will eventually expand the use of PDT. Here we offer a brief review of our own contribution to the development of a photosensitizer for PDT – redaporfin – currently in Phase II clinical trials, and present data on its combination with two glycolysis inhibitors: 2-deoxyglucose and 3-bromopyruvate. We show that 3-bromopyruvate is more cytotoxic to a carcinoma cell line (CT26) than to a normal fibroblast (3T3) cell line, and that this selectivity is maintained in the in vitro combination with redaporfin-PDT. This combination was investigated in BALB/c mice with large subcutaneous CT26 tumors and it is shown that the cure rate in the combination is higher (33% cures) than in PDT (11% cures) or in 3-bromopyruvate (no cures) alone. The combination of redaporfin-PDT with 3-bromopyruvate illustrates the potential of combination therapies and how PDT benefits can be enhanced by systemic drugs with complementary targets.     

Morphology of Imidazolium‐Based Ionic Liquids as Deposited by Vapor Deposition: Micro‐/Nanodroplets and Thin Films

The morphology of micro‐ and nanodroplets and thin films of ionic liquids (ILs) prepared through physical vapor deposition is presented. The morphology of droplets deposited on indium‐tin‐oxide‐coated glass is presented for the extended 1‐alkyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide ([C_nC₁im][Ntf₂]; n=1–8) series, and the results show the nanostructuration of ILs. The use of in‐vacuum energetic particles enhances/increases the nanodroplets mobility/coalescence mechanisms and can be a pathway to the fabrication of thin IL films.     

Polymer structure and the compensation effect of the diffusion pre-exponential factor and activation energy of a permeating solute

In the present work, the relation between the pre-exponential factor and the apparent activation energy of diffusion, ln D(0) = alpha + betaE(D), so-called compensation effect, is re-examined and critically discussed for diffusion of gases in rubbery and glassy polymers. In principle, the above equation could be derived from the enthalpy-entropy compensation in the framework of the transition state theory. However, one should consider the influence of the jump length term contained in the pre-exponential factor, which may be affected by permeating species and polymer properties. We found that parameter alpha depends on penetrant size and polymer properties, such as local chain mobility and free volume. This can be interpreted by the fact that the jump length is affected by both penetrant and polymer properties. Finally, methods for estimating the jump length are discussed.     

Simultaneous distillation-extraction of high-value volatile compounds from Cistus ladanifer L

The present paper describes a procedure to isolate volatiles from rock-rose (Cistus ladanifer L.) using simultaneous distillation-extraction (SDE). High-value volatile compounds (HVVC) were selected and the influence of the extraction conditions investigated. The effect of the solvent nature and extraction time on SDE efficiency was studied. The best performance was achieved with pentane in 1 h operation. The extraction efficiencies ranged from 65% to 85% and the repeatability varied between 4% and 6% (as a CV%).The C. ladanifer SDE extracts were analysed by headspace solid phase microextraction (HS-SPME) followed by gas chromatography with flame ionization detection (GC-FID). The HS-SPME sampling conditions such as fiber coating, temperature, ionic strength and exposure time were optimized. The best results were achieved with an 85 μm polyacrylate fiber for a 60 min headspace extraction at 40 °C with 20% (w/v) of NaCl. For optimized conditions the recovery was in average higher than 90% for all compounds and the intermediate precision ranged from 4 to 9% (as CV %). The volatiles α-pinene (22.2 mg g⁻¹ of extract), 2,2,6-trimethylcyclohexanone (6.1 mg g⁻¹ of extract), borneol (3.0 mg g⁻¹ of extract) and bornyl acetate (3.9 mg g⁻¹ of extract) were identified in the SDE extracts obtained from the fresh plant material.     

The degree of the bicanonical map of a surface with

In this note it is shown that, given a smooth minimal complex surface of general type with , , for which the bicanonical map is a morphism, the degree of is not 3. This completes our earlier results, showing that if is a minimal surface of general type with , such that is free, then the bicanonical map of can have degree 1, 2 or 4.

     

Solvent Mixture Optimization in the Extraction of Bioactive Compounds and Antioxidant Activities from Garlic (Allium sativum L.)

Garlic is a health promoter that has important bioactive compounds. The bioactive extraction is an important step in the analysis of constituents present in plant preparations. The purpose of this study is to optimize the extraction with the best proportion of solvents to obtain total phenolic compounds (TPC) and thiosulfinates (TS) from dried garlic powder, and evaluate the antioxidant activities of the optimized extracts. A statistical mixture simplex axial design was used to evaluate the effect of solvents (water, ethanol, and acetone), as well as mixtures of these solvents, after two ultrasound extraction cycles of 15 min. Results showed that solvent mixtures with a high portion of water and pure water were efficient for TPC and TS recovery through this extraction procedure. According to the regression model computed, the most significant solvent mixtures to obtain high TPC and TS recovery from dried garlic powder are, respectively, the binary mixture with 75% water and 25% acetone and pure water. These optimized extracts presented oxygen radical absorbance capacity. Pure water was better for total antioxidant capacity, and the binary mixture of water–acetone (75:25) was better for DPPH scavenging activity. These optimized extracts can be used for industrial and research applications.     

Pseudo-character expansions forU(N)-invariant spin models onCP N−1

We define a set of orthogonal functions on the complex projective spaceCP ^N–1, and compute their Clebsch-Gordan coefficients as well as a large class of 6-j symbols. We also provide all the needed formulae for the generation of high-temperature expansions forU(N)-invariant spin models defined onCP ^N–1.     

Analysis of fluid–structure interaction by an arbitrary Lagrangian–Eulerian finite element formulation

In this paper, the interaction fluid–rigid body is analysed by a finite element procedure that incorporates the arbitrary Lagrangian–Eulerian (ALE) method into a well‐known two‐step projection scheme. The flow is assumed to be two‐dimensional, incompressible and viscous, with no turbulence models being included. The flow past a circular cylinder at ℛℯ=200 is first analysed, for fixed and oscillating conditions. The dependence of lock‐in upon the shift between the mechanical and the Strouhal frequencies, for a given amplitude of forced vibration, is illustrated. The aerodynamic forces and the wake geometry are compared for locked‐in conditions with different driving frequencies. The behaviour of a rectangular cylinder (B/D=4) at ℛℯ=500 (based on height D) is also analysed. The flutter derivatives associated with aerodynamic damping (H₁* and A₂* in Scanlan's notation) are evaluated by the free oscillation method for several values of reduced flow speed above the Strouhal one (namely for 3≤U*≤8). Torsional flutter was attained at U*≥5, with all the other situations showing stable characteristics. Copyright © 1999 John Wiley & Sons, Ltd.     

Transient electric birefringence study of agarose aggregates in water-dimethyl sulphoxide mixtures

The dynamical behavior of agarose aggregates in a mixture of water and dimethyl sulphoxide (DMSO) has been investigated using a Transient Electric Birefringence (TEB) set up. Different agarose concentrations for different water/DMSO proportions were considered. The relaxation of the birefringence curves can be fitted with a stretched exponential of the form Δn(t) = Δn0 exp(-(Dt)^0.5). The exponent 0.5 suggests a high polydispersity of the aggregates. The rotational diffusion coefficient, D, depends strongly on the water/DMSO proportion. For small values of the applied electric field it presents a maximum for a water volume fraction equal to 0.5. A strong dependence of D on the applied electric field is also observed. However, the same kind of behavior as for weak fields is recovered when a subtle representation of the data is used. Differential Scanning Calorimetry (DSC) results also show a maximum in the temperature of fusion of the aggregates for a water volume fraction of 0.5. This set of results suggest strongly that « complexes » of water/DMSO/agarose are formed in the mixture and that the process of aggregate formation is more « efficient » for a water/DMSO mixture of same proportions.     

Universal families and quantum control in infinite dimensions

In a topological space, a family of continuous mappings is called universal if its action, in at least one element of the space, is dense. If the mappings are unitary or trace-preserving completely positive, the notion of universality is closely related to the notion of controllability in either closed or open quantum systems. Quantum controllability in infinite dimensions is discussed in this setting and minimal generators are found for full control universal families. Some of the requirements of the operators needed for control in infinite dimensions follow from the properties of the infinite unitary group. Hence, a brief discussion of this group and the appropriate mathematical spaces is also included.