On the feasibility of ultrasound Doppler-based personalized hemodynamic modeling of the abdominal aorta.

Background: Personalized modeling is a promising tool to improve abdominal aortic aneurysm (AAA) rupture risk assessment. Computed tomography (CT) and quantitative flow (Q-flow) magnetic resonance imaging (MRI) are widely regarded as the gold standard for acquiring patient-specific geometry and velocity profiles, respectively. However, their frequent utilization is hindered by various drawbacks.

Melanoma cells can be eliminated by sialylated CD43 × CD3 bispecific T cell engager formats in vitro and in vivo.

Targeted cancer therapy with monoclonal antibodies has proven successful for different cancer types but is limited by the availability of suitable antibody targets. CD43s, a unique sialylated form of CD43 expressed by hematologic malignancies, is a recently identified target and antibodies interacting with CD43s may have therapeutic potential against acute myeloid leukemia (AML) and myelodysplastic syndrome. CD43s is recognized by the human antibody AT1413, that was derived from a high-risk AML patient who successfully cleared leukemia after allogeneic stem cell transplantation.

Tumour-reactive B cells and antibody responses after allogeneic haematopoietic cell transplantation.

For many high-risk haematologic malignancies, such as acute myeloid leukaemia, the success of therapy relies mainly on invoking a curative antitumour immune response. This can be achieved by inducing a graft-versus-leukaemia response following allogeneic haematopoietic cell transplantation. While the contribution of T cells and natural killer cells to graft-versus-leukaemia responses is established, the contribution of B cells and antibodies is relatively unexplored.

A Chemo-enzymatically Linked Bispecific Antibody Retargets T Cells to a Sialylated Epitope on CD43 in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a high-risk disease with a poor prognosis, particularly in elderly patients. Because current AML treatment relies primarily on untargeted therapies with severe side effects that limit patient eligibility, identification of novel therapeutic AML targets is highly desired. We recently described AT1413, an antibody produced by donor B cells of a patient with AML cured after allogeneic hematopoietic stem cell transplantation.

Patient-derived antibody recognizes a unique CD43 epitope expressed on all AML and has antileukemia activity in mice.

Immunotherapy has proven beneficial in many hematologic and nonhematologic malignancies, but immunotherapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is hampered by the lack of tumor-specific targets. We took advantage of the tumor-immunotherapeutic effect of allogeneic hematopoietic stem cell transplantation and searched the B-cell repertoire of a patient with a lasting and potent graft-versus-AML response for the presence of AML-specific antibodies. We identified an antibody, AT1413, that was of donor origin and that specifically recognizes a novel sialylated epitope on CD43 (CD43s).

AML-specific cytotoxic antibodies in patients with durable graft-versus-leukemia responses.

Most patients with acute myeloid leukemia (AML) can only be cured when allogeneic hematopoietic stem-cell transplantation induces a graft-versus-leukemia immune response (GVL). Although the role of T cells and natural killer cells in tumor immunology has been established, less is known about the contribution of B cells. From B cells of high-risk patients with AML with potent and lasting GVL responses, we isolated monoclonal antibodies directed against antigens expressed on the cell surface of AML cells but not on normal hematopoietic and nonhematopoietic cells.

The modified FACS calcein AM retention assay: A high throughput flow cytometer based method to measure cytotoxicity.

Current methods to determine cellular cytotoxicity in vitro are hampered by background signals that are caused by auto-fluorescent target and effector cells and by non-specific cell death. We combined and adjusted existing cell viability assays to develop a method that allows for highly reproducible, accurate, single cell analysis by high throughput FACS, in which non-specific cell death is corrected for. In this assay the number of living, calcein AM labeled cells that are green fluorescent are quantified by adding a fixed number of unlabeled calibration beads to the analysis.

Triple helix formation in amphiphilic discotics: demystifying solvent effects in supramolecular self-assembly.

A set of chiral, amphiphilic, self-assembling discotic molecules based on the 3,3'-bis(acylamino)-2,2'-bipyridine-substituted benzene-1,3,5-tricarboxamide motif (BiPy-BTA) was prepared. Amphiphilicity was induced into the discotic molecules by an asymmetrical distribution of alkyl and oligo(ethylene oxide) groups in the periphery of the molecules. Small-angle X-ray scattering, cryogenic transmission electron microscopy, and circular dichroism spectroscopy measurements were performed on the discotic amphiphiles in mixtures of water and alcohol at temperatures between 0 °C an 90 °C.

Thioamides: versatile bonds to induce directional and cooperative hydrogen bonding in supramolecular polymers.

The amide bond is a versatile functional group and its directional hydrogen-bonding capabilities are widely applied in, for example, supramolecular chemistry. The potential of the thioamide bond, in contrast, is virtually unexplored as a structuring moiety in hydrogen-bonding-based self-assembling systems. We report herein the synthesis and characterisation of a new self-assembling motif comprising thioamides to induce directional hydrogen bonding.

Evaporative self-assembly of single-chain, polymeric nanoparticles.

Evaporative self-assembly of dilute solutions containing single-chain polymeric nanoparticles results in characteristic morphologies imaged using atomic force microscopy. Quantitative comparison of experimental data to morphologies obtained by lattice-gas simulations shows that the nonequilibrium patterns emerge from a complex interplay between dewetting, solvent evaporation and nanoparticle diffusion.

Orthogonal self-assembly in folding block copolymers.

We herein report the synthesis and characterization of ABA triblock copolymers that contain two complementary association motifs and fold into single-chain polymeric nanoparticles (SCPNs) via orthogonal self-assembly. The copolymers were prepared using atom-transfer radical polymerization (ATRP) and possess different pendant functional groups in the A and B blocks (alcohols in the A block and acetylenes in the B block). After postfunctionalization, the A block contains o-nitrobenzyl-protected 2-ureidopyrimidinone (UPy) moieties and the B block benzene-1,3,5-tricarboxamide (BTA) moieties.

Symmetry breaking in the self-assembly of partially fluorinated benzene-1,3,5-tricarboxamides.

The interplay of two subsequent aggregation processes results in a symmetry-breaking phenomenon in an achiral self-assembling system. Partially fluorinated benzene-1,3,5-tricarboxamide molecules self-assemble into a racemic mixture of one-dimensional P- and M-helical aggregates, followed by bundling into optically active higher-order aggregates or fibers.

Hydrogen bonding directed supramolecular polymerisation of oligo(phenylene-ethynylene)s: cooperative mechanism, core symmetry effect and chiral amplification.

The design of supramolecular motifs with tuneable stability and adjustable supramolecular polymerisation mechanisms is of crucial importance to precisely control the properties of supramolecular assemblies. This report focuses on constructing π-conjugated oligo(phenylene ethynylene) (OPE)-based one-dimensional helical supramolecular polymers that show a cooperative growth mechanism. Thus, a novel set of discotic molecules comprising a rigid OPE core, three amide groups, and peripheral solubilising wedge groups featuring C(3) and C(2) core symmetry was designed and synthesised.

Single-chain folding of polymers for catalytic systems in water.

Enzymes are a source of inspiration for chemists attempting to create versatile synthetic catalysts. In order to arrive at a polymeric chain carrying catalytic units separated spatially, it is a prerequisite to fold these polymers in water into well-defined compartmentalized architectures thus creating a catalytic core. Herein, we report the synthesis, physical properties, and catalytic activity of a water-soluble segmented terpolymer in which a helical structure in the apolar core is created around a ruthenium-based catalyst.

Simultaneous measurement of RBC velocity, flux, hematocrit and shear rate in vascular networks.

Not all tumor vessels are equal. Tumor-associated vasculature includes immature vessels, regressing vessels, transport vessels undergoing arteriogenesis and peritumor vessels influenced by tumor growth factors. Current techniques for analyzing tumor blood flow do not discriminate between vessel subtypes and only measure average changes from a population of dissimilar vessels.

Reduction of calcification of carbodiimide-processed heart valve tissue by prior blocking of amine groups with monoaldehydes.

Background And Aim Of The Study: Failure of implanted bioprostheses due to calcification is a commonly occurring phenomenon. In order to prevent calcification, many alternative cross-linking methods to glutaraldehyde (GA) have been developed and evaluated.

Methods: In a novel approach an improved carbodiimide (EDC) cross-linking method that comprises a two-step process was developed.