Probing Rotational Decoherence with a Trapped-Ion Planar Rotor.

The quantum rotor is one of the simplest model systems in quantum mechanics, but only in recent years has theoretical work revealed general fundamental scaling laws for its decoherence. For example, a superposition of orientations decoheres at a rate proportional to the sine squared of the angle between them. Here, we observe scaling laws for rotational decoherence dynamics for the first time, using a 4  μm diameter planar rotor composed of two Paul-trapped ions.

Expanding the Genetic Etiology of Multiple Morphological Abnormalities of the Sperm Flagella: A Case Report of Two Novel DNAH1 Variants.

Background: The following case report details the genetic evaluation and treatment of a 30-year-old male with a history of asthenoteratospermia and notable abnormalities of the sperm flagella.

Methods: Genetic evaluation was performed via a multi-gene panel of genes associated with primary ciliary dyskinesia and multiple morphological abnormalities of the sperm flagella (MMAF) prior to the couple's in vitro fertilization (IVF) cycle.

Results: Genetic evaluation was performed via a multi-gene panel of genes associated with primary ciliary dyskinesia and multiple morphological abnormalities of the sperm flagella (MMAF) prior to the couple's in vitro fertilization (IVF) cycle.

Non-Hermitian dynamics and non-reciprocity of optically coupled nanoparticles.

Non-Hermitian dynamics, as observed in photonic, atomic, electrical and optomechanical platforms, holds great potential for sensing applications and signal processing. Recently, fully tuneable non-reciprocal optical interaction has been demonstrated between levitated nanoparticles. Here we use this tunability to investigate the collective non-Hermitian dynamics of two non-reciprocally and nonlinearly interacting nanoparticles.

Evolution of the clinical-stage hyperactive TcBuster transposase as a platform for robust non-viral production of adoptive cellular therapies.

Cellular therapies for the treatment of human diseases, such as chimeric antigen receptor (CAR) T and natural killer (NK) cells have shown remarkable clinical efficacy in treating hematological malignancies; however, current methods mainly utilize viral vectors that are limited by their cargo size capacities, high cost, and long timelines for production of clinical reagent. Delivery of genetic cargo via DNA transposon engineering is a more timely and cost-effective approach, yet has been held back by less efficient integration rates. Here, we report the development of a novel hyperactive TcBuster (TcB-M) transposase engineered through structure-guided and in vitro evolution approaches that achieves high-efficiency integration of large, multicistronic CAR-expression cassettes in primary human cells.

Physicochemical Property Determinants of Oral Absorption for PROTAC Protein Degraders.

Heterobifunctional PROTAC degraders are gaining attention as a differentiated therapeutic modality with the potential for oral dosing in the clinic. Belonging to the beyond Rule of Five domain of physicochemical property space, we have sought to understand the determinants of oral absorption for this class of molecules for the rapid development of novel oral agents. We have collected a large data set from PROTAC molecules that have been dosed orally and intravenously in rats to estimate the fraction absorbed from oral dosing.

Erratum: Gas-induced friction and diffusion of rigid rotors [Phys. Rev. E 97, 052112 (2018)].

This corrects the article DOI: 10.1103/PhysRevE.97.

Macroscopic Quantum Test with Bulk Acoustic Wave Resonators.

Recently, solid-state mechanical resonators have become a platform for demonstrating nonclassical behavior of systems involving a truly macroscopic number of particles. Here, we perform the most macroscopic quantum test in a mechanical resonator to date, which probes the validity of quantum mechanics by ruling out a classical description at the microgram mass scale. This is done by a direct measurement of the Wigner function of a high-overtone bulk acoustic wave resonator mode, monitoring the gradual decay of negativities over tens of microseconds.

Protein degraders enter the clinic - a new approach to cancer therapy.

Heterobifunctional protein degraders, such as PROteolysis TArgeting Chimera (PROTAC) protein degraders, constitute a novel therapeutic modality that harnesses the cell's natural protein-degradation machinery - that is, the ubiquitin-proteasome system - to selectively target proteins involved in disease pathogenesis for elimination. Protein degraders have several potential advantages over small-molecule inhibitors that have traditionally been used for cancer treatment, including their event-driven (rather than occupancy-driven) pharmacology, which permits sub-stoichiometric drug concentrations for activity, their capacity to act iteratively and target multiple copies of a protein of interest, and their potential to target nonenzymatic proteins that were previously considered 'undruggable'. Following numerous innovations in protein degrader design and rigorous evaluation in preclinical models, protein degraders entered clinical testing in 2019.

Force-Gradient Sensing and Entanglement via Feedback Cooling of Interacting Nanoparticles.

We show theoretically that feedback cooling of two levitated, interacting nanoparticles enables differential sensing of forces and the observation of stationary entanglement. The feedback drives the two particles into a stationary, nonthermal state which is susceptible to inhomogeneous force fields and which exhibits entanglement for sufficiently strong interparticle couplings. We predict that force-gradient sensing at the zepto-Newton per micron range is feasible and that entanglement due to the Coulomb interaction between charged particles can be realistically observed in state-of-the-art setups.

Tunable light-induced dipole-dipole interaction between optically levitated nanoparticles.

Arrays of optically trapped nanoparticles have emerged as a platform for the study of complex nonequilibrium phenomena. Analogous to atomic many-body systems, one of the crucial ingredients is the ability to precisely control the interactions between particles. However, the optical interactions studied thus far only provide conservative optical binding forces of limited tunability.

Natural deep eutectic systems for nature-inspired cryopreservation of cells.

Natural deep eutectic systems (NADES) are emerging as potential cryoprotective agents (CPA) for cell preservation. In this investigation, we develop an optimized CPA formulation using trehalose-glycerol NADES (T:G) diluted in Normosol-R and supplemented with isoleucine. Differential scanning calorimetry (DSC) is used to define the thermophysical properties of NADES-based solutions, and Raman spectroscopy is used to characterize the effect of NADES on ice formation and hydrogen bonding.

Cooling Nanorotors by Elliptic Coherent Scattering.

Simultaneously cooling the rotational and translational motion of nanoscale dielectrics into the quantum regime is an open task of great importance for sensing applications and quantum superposition tests. Here, we show that the six-dimensional ground state can be reached by coherent-scattering cooling with an elliptically polarized and shaped optical tweezer. We determine the cooling rates and steady-state occupations in a realistic setup and discuss applications for mechanical sensing and fundamental experiments.

Bragg Diffraction of Large Organic Molecules.

We demonstrate Bragg diffraction of the antibiotic ciprofloxacin and the dye molecule phthalocyanine at a thick optical grating. The observed patterns show a single dominant diffraction order with the expected dependence on the incidence angle as well as oscillating population transfer between the undiffracted and diffracted beams. We achieve an equal-amplitude splitting of 14ℏk (photon momenta) and maximum momentum transfer of 18ℏk.

Understanding the freezing responses of T cells and other subsets of human peripheral blood mononuclear cells using DSMO-free cryoprotectants.

Background: This study examined the freezing responses of peripheral blood mononuclear cells (PBMCs) and specific white blood cell subsets contained therein when cryopreserved in three combinations of osmolytes composed of sugars, sugar alcohols and amino acids.

Methods: A differential evolution algorithm with multiple objectives was used to optimize cryoprotectant composition and thus the post-thaw recoveries for both helper and cytotoxicity T cells simultaneously.

Results: The screening of various formulations using a differential evolution algorithm showed post-thaw recoveries greater than 80% for the two subsets of T cells.

Cryopreservation of Human iPS Cell Aggregates in a DMSO-Free Solution-An Optimization and Comparative Study.

Human induced pluripotent stem cells (hiPSCs) are an important cell source for regenerative medicine products. Effective methods of preservation are critical to their clinical and commercial applications. The use of a dimethyl sulfoxide (DMSO)-free solution containing all non-toxic molecules offers an effective alternative to the conventional DMSO and alleviates pain points associated with the use of DMSO in the cryopreservation of hiPSCs.

Cryopreservation of Hematopoietic Stem Cells: Emerging Assays, Cryoprotectant Agents, and Technology to Improve Outcomes.

Hematopoietic stem cell (HSC) therapy is widely used to treat a growing number of hematological and non-hematological diseases. Cryopreservation of HSCs allows for cells to be transported from the site of processing to the site of clinical use, creates a larger window of time in which cells can be administered to patients, and allows sufficient time for quality control and regulatory testing. Currently, HSCs and other cell therapies conform to the same cryopreservation techniques as cells used for research purposes: cells are cryopreserved in dimethyl sulfoxide (DMSO) at a slow cooling rate.

Rotational Alignment Decay and Decoherence of Molecular Superrotors.

We present the quantum master equation describing the coherent and incoherent dynamics of a rapidly rotating molecule in the presence of a thermal background gas. The master equation relates the rate of rotational alignment decay and decoherence to the microscopic scattering amplitudes, which we calculate for anisotropic van der Waals scattering. For large rotational energies, we find quantitative agreement of the resulting alignment decay rate with recent superrotor experiments.

Conformer Selection by Matter-Wave Interference.

We establish that matter-wave diffraction at near-resonant ultraviolet optical gratings can be used to spatially separate individual conformers of complex molecules. Our calculations show that the conformational purity of the prepared beam can be close to 100% and that all molecules remain in their electronic ground state. The proposed technique is independent of the dipole moment and the spin of the molecule and thus paves the way for structure-sensitive experiments with hydrocarbons and biomolecules, such as neurotransmitters and hormones, which have evaded conformer-pure isolation so far.

Rotational Friction and Diffusion of Quantum Rotors.

We present the Markovian quantum master equation describing rotational decoherence, friction, diffusion, and thermalization of planar, linear, and asymmetric rotors in contact with a thermal environment. It describes how an arbitrary initial rotation state decoheres and evolves toward a Gibbs-like thermal ensemble, as we illustrate numerically for the linear and the planar top, and it yields the expected rotational Fokker-Planck equation of Brownian motion in the semiclassical limit.

Gas-induced friction and diffusion of rigid rotors.

We derive the Boltzmann equation for the rotranslational dynamics of an arbitrary convex rigid body in a rarefied gas. It yields as a limiting case the Fokker-Planck equation accounting for friction, diffusion, and nonconservative drift forces and torques. We provide the rotranslational friction and diffusion tensors for specular and diffuse reflection off particles with spherical, cylindrical, and cuboidal shape, and show that the theory describes thermalization, photophoresis, and the inverse Magnus effect in the free molecular regime.

Dihydrobenzisoxazole-4-one compounds are novel selective inhibitors of aldosterone synthase (CYP11B2) with in vivo activity.

6,7-Dihydro-5H-2,1-benzisoxazol-4-one analogs are potent inhibitors of aldosterone synthase (CYP11B2) with selectivity over the highly homologous enzyme cortisol synthase (CYP11B1). These compounds are unique among inhibitors of CYP11B2 in their lack of a strong-heme binding group such as a pyridine or imidazole. Poor metabolic stability in hepatocyte incubations was found to proceed via a reduction of the isoxazole ring.