An Amino-Chain Modified β-cyclodextrin: A Supramolecular Ligand for Pd(OAc)2 Acceleration in Suzuki–Miyaura Coupling Reactions in Water

A well-designed and synthesized water-soluble class of β-cyclodextrin supported palladium complex PdLn@Et-β-CD could efficiently validate high catalytic activity and act as a supramolecular platform for phosphine-free Suzuki–Miyaura cross‐coupling reactions between arylboronic acid/ arylboronic ester and aryl halides in water under mild conditions. The presented novel PdLn@Pr-β-CD complex catalyst was characterized by NMR, XRD, FT-IR, and DSC analysis. Furthermore, the role of the PdLn@Et-β-CD fragment in the reaction mechanism studied by molecular complexation was proposed based on FT-IR, 2D NMR (ROESY) spectroscopy, FE-SEM, and DSC spectroscopic analysis. The important benefits of this technique comprise simple phosphine-free preparation of the palladium catalyst, a wide range of functional-group tolerance, and easy recyclability; this method, furthermore, eschews hazardous reagents or solvents.

14-3-3 protein and ATRAP bind to the soluble class IIB phosphatidylinositol transfer protein RdgBβ at distinct sites

PITPs (phosphatidylinositol transfer proteins) are characterized by the presence of the PITP domain whose biochemical properties of binding and transferring PI (phosphatidylinositol) are well studied. Despite their wide-spread expression in both unicellular and multicellular organisms, they remain functionally uncharacterized. An emerging theme is that individual PITPs play highly specific roles in either membrane trafficking or signal transduction. To identify specific roles for PITPs, identification of interacting molecules would shed light on their molecular function. In the present paper, we describe binding partners for the class IIB PITP RdgBβ (retinal degeneration type Bβ). RdgBβ is a soluble PITP but is unique in that it contains a region of disorder at its C-terminus following its defining N-terminal PITP domain. The C-terminus of RdgBβ is phosphorylated at two serine residues, Ser274 and Ser299, which form a docking site for 14-3-3 proteins. Binding to 14-3-3 proteins protects RdgBβ from degradation that occurs at the proteasome after ubiquitination. In addition to binding 14-3-3, the PITP domain of RdgBβ interacts with the Ang II (angiotensin II)-associated protein ATRAP (Ang II receptor-associated protein). ATRAP is also an interacting partner for the AT1R (Ang II type 1 receptor). We present a model whereby RdgBβ functions by being recruited to the membrane by ATRAP and release of 14-3-3 from the C-terminus allows the disordered region to bind a second membrane to create a membrane bridge for lipid transfer, possibly under the control of Ang II.

In vitro expansion of CMV-specific CD4+ T-cells by artificial antigen presentation for adoptive immunotherapy in the post- transplant setting

3049 Background: CMV continues to be a major cause of morbidity and mortality in marrow allograft recipients. The importance of CD4+ T-cells in maintaining immunity and therapeutic efficacy in adoptive cellular strategies has been appreciated. With a novel artificial antigen presenting cell (AAPC) system, we induced the expansion of CMV-specific CD4+ T-cells. Methods: AAPCs were generated by using a standardizable line of murine 3T3 cells sequentially transduced to express human ICAM-1, LFA-1, B7.1, HLA A*0201 and DRB1*1101 alleles. Antigen was provided either by peptide pulsing with the HLA-DRB1*1101-restricted, CMV- pp65-derived P92 peptide, or the influenza matrix peptide (IMP) as a control, or by transgene expression of pp65. PBMCs were isolated from a CMV+, HLA*A02, DRB1*11-positive healthy donor after informed consent, and enriched for T-cells via positive selection using sheep RBCs. Cocultures of T-cells with AAPCs were established at a ratio of 10:1. 20 IU/ml of IL-2 was added on d7 and every third day thereafter. On d12- 14 of co-culture, the T-cells were restimulated on a fresh monolayer of AAPCs with antigen. Cells were counted in triplicate via hemocytometer with trypan blue exclusion. Immunophenotyping of expanded T-cells was done via flow cytometric analysis for cell surface expression of CD3, CD8, CD4, and soluble Class II (HLA-DRB1*1101) tetramer specific for the P92 peptide of CMV-pp65. Results: Following 3 rounds of stimulation, antigen-specific fold expansion, defined by DR11,P92-tetramer-positive, CD4+ T-cells, was 313-fold when stimulated on AAPC.A2.DR11.PP65, compared to 5–35-fold using the other AAPC controls. Conclusion: We are able to expand clinically relevant numbers of CMV-specific CD4+ T-cells using a rapid, practicable, and broadly applicable approach. These preclinical studies show the feasibility of generating virus-specific T-cells of desired specificity and HLA restriction for adoptive immunotherapy of severe CMV infections. [Table: see text] No significant financial relationships to disclose.

Explicit Gittins Indices for a Class of Superdiffusive Processes

We explicitly calculate the dynamic allocation indices (i.e. the Gittins indices) for multi-armed Bandit processes driven by superdiffusive noise sources. This class of model generalizes former results derived by Karatzas for diffusive processes. In particular, the Gittins indices do, in this soluble class of superdiffusive models, explicitly depend on the noise state.

Explicit Gittins Indices for a Class of Superdiffusive Processes

We explicitly calculate the dynamic allocation indices (i.e. the Gittins indices) for multi-armed Bandit processes driven by superdiffusive noise sources. This class of model generalizes former results derived by Karatzas for diffusive processes. In particular, the Gittins indices do, in this soluble class of superdiffusive models, explicitly depend on the noise state.

Explicit Gittins Indices for a Class of Superdiffusive Processes

We explicitly calculate the dynamic allocation indices (i.e. the Gittins indices) for multi-armed Bandit processes driven by superdiffusive noise sources. This class of model generalizes former results derived by Karatzas for diffusive processes. In particular, the Gittins indices do, in this soluble class of superdiffusive models, explicitly depend on the noise state.