Exploring wavepacket dynamics behind strong-field momentum-dependent photodissociation in CH(2)BrI(+).

The ultrafast photodissociation dynamics of CH(2)BrI(+) into CH(2)Br(+) + I is studied using high level ab initio electronic structure calculations in conjunction with integration of the time-dependent Schrödinger equation and compared with measured pump-probe signals. These pump-probe measurements provide evidence for momentum-dependent dissociation, which is interpreted using two theoretical models. The first is based on DFT and TD-DFT calculations neglecting spin-orbit coupling, while the other, more rigorous model employs a larger number of coupled multi-configurational potentials obtained by means of CASSCF calculations. The latter model highlights the role of spin-orbit coupling between ionic electronic states as well as the effect of strong fields in the quantum dynamics including Stark-shifts and multi-photon excitation.

Peptide-TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens.

Personalized cancer vaccines targeting patient-specific neoantigens are a promising cancer treatment modality; however, neoantigen physicochemical variability can present challenges to manufacturing personalized cancer vaccines in an optimal format for inducing anticancer T cells. Here, we developed a vaccine platform (SNP-7/8a) based on charge-modified peptide-TLR-7/8a conjugates that are chemically programmed to self-assemble into nanoparticles of uniform size (~20 nm) irrespective of the peptide antigen composition. This approach provided precise loading of diverse peptide neoantigens linked to TLR-7/8a (adjuvant) in nanoparticles, which increased uptake by and activation of antigen-presenting cells that promote T-cell immunity. Vaccination of mice with SNP-7/8a using predicted neoantigens (n = 179) from three tumor models induced CD8 T cells against ~50% of neoantigens with high predicted MHC-I binding affinity and led to enhanced tumor clearance. SNP-7/8a delivering in silico-designed mock neoantigens also induced CD8 T cells in nonhuman primates. Altogether, SNP-7/8a is a generalizable approach for codelivering peptide antigens and adjuvants in nanoparticles for inducing anticancer T-cell immunity.

Pulse-shaping multiphoton FRET microscopy.

Fluorescence Resonance Energy Transfer (FRET) microscopy is a commonly-used technique to study problems in biophysics that range from uncovering cellular signaling pathways to detecting conformational changes in single biomolecules. Unfortunately, excitation and emission spectral overlap between the fluorophores create challenges in quantitative FRET studies. It has been shown previously that quantitative FRET stoichiometry can be performed by selective excitation of donor and acceptor fluorophores. Extending this approach to two-photon FRET applications is difficult when conventional femtosecond laser sources are used due to their limited bandwidth and slow tuning response time. Extremely broadband titanium:sapphire lasers enable the simultaneous excitation of both donor and acceptor for two-photon FRET, but do so without selectivity. Here we present a novel two-photon FRET microscopy technique that employs pulse-shaping to perform selective excitation of fluorophores in live cells and detect FRET between them. Pulse-shaping via multiphoton intrapulse interference can tailor the excitation pulses to achieve selective excitation. This technique overcomes the limitation of conventional femtosecond lasers to allow rapid switching between selective excitation of the donor and acceptor fluorophores. We apply the method to live cells expressing the fluorescent proteins mCerulean and mCherry, demonstrating selective excitation of fluorophores via pulse-shaping and the detection of two-photon FRET. This work paves the way for two-photon FRET stoichiometry.

Molecular fragmentation driven by ultrafast dynamic ionic resonances.

The authors time resolve molecular motion in bound state, ionic potentials that leads to bond cleavage during the interaction with intense, ultrafast laser fields. Resonances in molecular ions play an important role in dissociative ionization with ultrafast laser fields, and the authors demonstrate how these resonances evolve in time to produce dissociation after initial strong-field ionization. Exploiting such dynamic resonances offers the possibility of controlled bond breaking and characterizing time-dependent molecular structure.