Reduced statistical fluctuations of the position of an object partitioning in two its environment

Through hard‐disk simulations and theoretical considerations on the movement of an object that partitions a microtubule filled with small particles, we find that the vibrations typical of thermal equilibrium are reached after a time that increases exponentially with the number of particles involved. The result is a mechanism capable of breaching, on accessible time scales, the ergodic constraints in nano‐scale systems

Three-dimensional optical beam propagation and solitons in photorefractive crystals

The model equations for beam propagation in photorefractive material are simplified under appropriate conditions. The possibility of obtaining bright and dark screening soliton solutions in 2+12+1 dimensions is investigated, and, whenever possible, their amplitude–size relation is displayed

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Studies on O-alkylisoureas in solution phase and on solid support

The use of polymer-supported reagents is proving to be an ideal methodology for the clean and efficient preparation of chemical libraries.  Polymer-supported reagents for the oxidation of alcohols and for the O-alkylation of carboxylic acids were studied.  Several polymer-supported sulfoxides were prepared in order to accomplish catch-and-release oxidations of primary and secondary alcohols.  Unfortunately, an efficient protocol for the oxidations with purification of the intermediate polymer-supported sulfoxonium ion could not be achieved. A protocol for the synthesis of polymer-supported O-alkylisoureas was developed, and the isoureas thus obtained proved to be excellent reagents for the O-alkylation of carboxylic acids.  The usefulness of microwave irradiation to accelerate the esterification reactions was demonstrated.  The use of polymer-supported isoureas as intermediates in a catch-and-release esterification procedure was also investigated. Some novel reactions of O-alkylisoureas were investigated in solution phase.  Alcohols could be O-benzylated using O-benzylisourea with Lewis acid catalysis.  Isoureas were used as reactive intermediates for the cyclisations of β-hydroxyamides to form 2-oxazolines and of N-hydroxyalkylsulfonamides to form cyclic sulfonamides. Finally, a new activation mechanism for the reactions of isoureas using acetyl halides has been discovered, and applied to an efficient one-pot conversion of alcohols into haloalkanes.</p

Studies on O-alkylisoureas in solution phase and on solid support

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A practical synthesis of a high-loading solid-supported IBX amide for the oxidation of alcohols

A straightforward three-step synthesis of a solid-supported IBX amide resin was achieved using inexpensive and commercially available 2-iodobenzoic acid chloride and Merrifield resin. A high apparent loading of 0.63 mmol g?1 was obtained. Oxidation of a range of alcohols to the corresponding carbonyl compounds proved very straightforward using 1.2 equiv of the resin. Recycling of the resin was also possible with minimal loss of activity after two reoxidations

A mild, phosphine-free method for the conversion of alcohols into halides (Cl, Br, I) via the corresponding O-alkyl isoureas

A novel procedure for the conversion of primary and secondary alcohols into the corresponding alkyl chlorides, bromides and iodides is described. The transformation is high-yielding in the case of chlorides and bromides, tolerates a range of functional groups, and does not rely on the use of phosphines

Polymer-supported O-alkylisoureas: useful reagents for the O-alkylation of carboxylic acids

Polymer-supported O-alkylisoureas were prepared by reaction of an alcohol with a polymer-supported carbodiimide under copper(II) catalysis. These reagents were used to transform carboxylic acids into the corresponding methyl, benzyl, allyl, and p-nitrobenzyl esters in a highly chemoselective manner in high yields and in very high purity after simple resin filtration and solvent evaporation. The reactions could be carried out using both conventional or microwave heating, with reaction times as short as 3-5 min in the latter case, without compromising yield, purity, or chemoselectivity. Unfortunately, the corresponding solid-supported tert-butyl isoureas could not be prepared

Microwaves, supported-reagents and parallel synthesis: isocyanide and ester synthesis

The benefits of microwave irradiation are described for a number of important reactions such as amid and ester formation and dehydration of formamide to the corresponding isonitriles. Not only were reaction times dramatically reduced but the transformations were less prone to side reactions and decomposition