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Two-pulse COSY (correlation spectroscopy) EPR (Electron Paramagnetic resonance) sequence, utilized for distance measurements in biological systems using nitroxide biradicals, is investigated both analytically and numerically. The analytical expressions derived here for any orientations of the two nitroxide dipoles with respect to the dipolar axis, oriented at an angle \theta with respect to the magnetic field with respect to the dipolar axis joining the two nitroxide dipoles at the angle, \theta, show that, in general, the coherence transfer from p=0 to the single quantum p=1 state is peaked at the orientation \theta being the magic-angle, {54.7}^\circle, and its supplementary angle, {125.3}^\circle, with a narrow width, implying that there is produced orientational selectivity, by the first \pi/2 pulse. This results in the signal being predominantly determined by those biradicals, whose dipolar axes are at, or near, the magic and its supplementary angle. This is entirely a novel finding, not published in the literature. Furthermore, the analytical treatment shows that the Fourier transforms of the two-pulse COSY signal exhibit peaks at \pm d\times \left(3cos^2\theta-1\right); here d=\frac{2}{3}D, with D being the dipolar-coupling constant.). In addition, there occurs also structural sensitivity of the signal, i.e., its dependence on the orientations of the two nitroxide dipoles during to free evolution over the two coherence states p=+1 and -1. The powder (polycrystalline) averages over the unit sphere, accumulated over 20 sets of Monte-Carlo orientations of the two nitroxide dipole moments reveal that the Pake doublets occur at \pm d. It is concluded that the two-pulse COSY experiment is a preferred technique for distance measurements as compared to other multi-pulse (four, five, six) sequences, as well as two-pulse DQ (double quantum) and five-pulse DQM (double quantum modulation) sequences, because its Pake doublet is the most intense of all the other multi-pulse sequences.

CAP Virtual Congress 2021

Magic-angle orientation selectivity in two-pulse EPR COSY (correlation spectroscopy) sequence: Distance measurements in biological systems

liouville-von neumann equation

correlation spectroscopy (cosy)

pulsed epr

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technical paper

While Big Bang cosmology successfully explains much of the history of our universe, there are certain features it does not explain, for example the spatial flatness and uniformity of our universe. One widely studied explanation for these features is cosmological inflation. I will discuss the gravitational wave spectra generated by inflaton field configurations oscillating after inflation for E-Model, T-Model, and additional inflationary models. I will show that these gravitational wave spectra provide access to some inflation models beyond the reach of any planned cosmic microwave background (CMB) experiments, such as LiteBIRD, Simons Observatory, and CMB-S4. Specifically, while these experiments will be able to resolve a tensor-to-scalar ratio ($r$) down to $10^{-3}$, I show that gravitational wave background measurements have the potential to probe certain inflation models for $r$ values down to $10^{-10}$. Importantly, all the gravitational wave spectra from E- and T-model inflation lie in the MHz-GHz frequency range, motivating development of gravitational wave detectors in this range.

Gravitational Wave Backgrounds from Low Scale Inflation

The CLS2 is a concept design of a next generation synchrotron light source to keep Canada at the forefront of scientific research that is uniquely available to researchers with access to such national infrastructure. Canada's research priorities in health and medicine, agriculture and food security, advance materials and industrial research, will all be enabled with national access to a next generation synchrotron. The CLS has provided critical research for Canada and the world, including covid-19 research that can only be performed on a synchrotron, and all OECD countries are in the process of commissioning, investing in or planning a next generation light source such as CLS2. This presentation of a new concept for a next generation synchrotron is a world leading design with the highest brightness in its class. The Conceptual Design Report currently being written is aimed at the government, industry and scientific community who will be the users of the facility and to engage them in the creation of a Technical Design Report and a project proposal to realise a future light source for Canada beyond the CLS which is approaching end-of-life.

A Next Generation Light Sournce for Canada

Radiotherapy and chemotherapy are the gold standard for treating patients with cancer in the clinic but, despite modern advances, are limited by normal tissue toxicity. The use of nanomaterials, such as gold nanoparticles (GNPs), to improve radiosensitivity and act as drug delivery systems can mitigate toxicity while increasing deposited tumor dose. To expedite a quicker clinical translation, three-dimensional (3D) tumor spheroid models that can better approximate the tumor environment compared to a two-dimensional (2D) monolayer model have been used. We tested the uptake of 15 nm GNPs and 50 nm GNPs on a monolayer and on spheroids of two cancer cell lines, CAL-27 and HeLa, to evaluate the differences between a 2D and 3D model in similar conditions. The anticancer drug docetaxel (DTX) which can act as a radiosensitizer, was also utilized, informing future potential of GNP-mediated combined therapeutics. The radiosensitization effects on monolayer vs spheroids with the different sized GNPs was also elucidated. In the 2D monolayer model, the addition of DTX induced a small, non-significant increase of uptake of GNPs of approximately 20% while in the 3D spheroid model, DTX increased uptake by between 50% and 200%, with CAL-27 having a much larger increase relative to HeLa. Further, the depth of penetration of 15 nm GNPs over 50 nm GNPs increased for both cancer spheroids. Measurement of the responses to radiation with GNPs yielded a large radiosensitization effect, with more of the cells on the periphery of the spheroid being affected. These results highlight the necessity to optimize GNP treatment conditions in a more realistic tumor-life environment. A 3D spheroid model can capture important details, such as different packing densities from different cancer cell lines and the introduction of an extracellular matrix, which are absent from a simple 2D monolayer model.

Three-dimensional tumor spheroids as a tool to optimize the nano-bio interface

Theories of Quantum Gravity predict a minimum measurable length and a corresponding modification of the Heisenberg Uncertainty Principle to the so-called Generalized Uncertainty Principle (GUP). However, this modification is non-relativistic, making it unclear whether the minimum length is Lorentz invariant. We formulate a Relativistic Generalized Uncertainty Principle, resulting in a Lorentz invariant minimum measurable length and the resolution of the composition law problem. This proved to be an important step in the formulation of Quantum Field Theory with minimum length. We derived the Lagrangians consistent with the existence of minimal length and describing the behaviour of scalar, spinor, and $U(1)$ gauge fields. We calculated the Feynman rules (propagators and vertices) associated with these Lagrangians. Furthermore, we calculated the Quantum Gravity corrected scattering cross-sections for a lepton-lepton scattering. Finally, we compared our results with current experiments, which allowed us to improve the bounds on scale at which quantum gravity phenomena will become relevant.

Quantum field theory with minimum length

Effective local therapy is needed to avoid local progression of the tumor, which may further decrease the development of systemic metastases and increase the possibility for resection. Radiation therapy (RT) is frequently used to locally treat the tumor. One of the major issues in RT for treating cancer is the close proximity of adjacent organs at risk, resulting in treatments doses being limited by significant tissue toxicities, preventing dose escalation necessary to guarantee local control. One of the currently adapted approaches to overcome this challenge is to add radiosensitizers to current RT protocol to unlock the full potential of RT. In this talk, I will focus on gold nanoparticles (GNPs), docetaxel, and cisplatin as radiosensitizers. About half of cancer patients (50%) receive radiotherapy, and all of these patients would benefit from this type of novel approaches.

Combining gold nanoparticles with other radiosensitizers for unlocking the full potential of cancer radiotherapy

Blister formation occurs when a laser pulse is focussed through a transparent substrate onto a coated polymer thin film. A pocket of expanding vapor is formed beneath the film, which pushes the film upward locally. This process has been used for Laser-Induced Forward Transfer (LIFT) of materials. Most studies of blister formation and blister-based LIFT use linear absorption of nanosecond or picosecond lasers to obtain large target areas (~100s of µm$^2$). We are the first to achieve nanoscale blisters, through nonlinear absorption of femtosecond pulses.

We spin-coated polyimide films achieving a thickness of 1.3 µm. We used a Ti:Sapphire laser producing pulses of 45-fs duration at a central wavelength of 800 nm. We mounted samples onto a 3D motion stage, and focused single pulses of various energies through the glass substrate onto the polymer-glass interface. Since polyimide is transparent to 800 nm light, we used tightly-focused (NA ≥ 0.4) femtosecond pulses to induce nonlinear absorption. We characterized samples after blister fabrication using atomic force microscopy (AFM). At intensities above 10$^{13}$ W/cm$^2$, interactions of the pulse with both the film and substrate must be considered. We model these interactions and find that the resulting blister volume is proportional to the energy deposited in the film.

The use of 0.95 NA focusing led to a minimum structure diameter of 700 nm, smaller than the wavelength of the laser pulse. In the future, we propose the use of thinner films and shorter wavelengths to reach further into the nanoscale. This technique can be used for direct micro- and nano-fabrication, and potentially to LIFT sensitive materials on the nanoscale. It is a possible alternative to lithography, laser milling, and laser-based additive machining that also leaves the surface composition unchanged, since the laser energy is deposited beneath the film.

Nanoscale polymer blister formation using single femtosecond pulses

The prototypical superfluid, Helium-4 ($^4$He), transitions to its superfluid state below ~2 K. In contrast, its isotopic counterpart Helium-3 ($^3$He) has a transition temperature of ~2 mK. This thousand-fold disparity is due to the nature of the superfluid transition; while $^4$He Bose condenses directly, the fermionic $^3$He atoms must first form composite bosons through Cooper pairing. The $p$-wave, spin-triplet pairing of the $^3$He atoms gives rise to many possible superfluid phases, though only two distinct phases are realized in the bulk.

Recent experimental and theoretical advances have suggested that a third phase emerges when superfluid $^3$He is confined to a slab --- a pair-density-wave (PDW) phase. Analogous to a supersolid, the PDW phase is characterized by the spontaneous breaking of translational symmetry that coexists with superfluid order. The precise spatial structure of this "superfluid crystal" has been the subject of ongoing debate: existing theories favor a unidirectional PDW, the stripe phase, while recent nuclear magnetic resonance (NMR) experiments seem to indicate a two-dimensional PDW with square or hexagonal symmetry. In this talk, I will outline a mechanism, based on Landau's theory of weak crystallization, which stabilizes a two-dimensional PDW with the hexagonal symmetry of a triangular lattice.

Triangular Pair-Density-Wave in Confined Superfluid 3He

The main advantage of hybrid PET-MR imaging systems is the ability to correlate anatomical with metabolic information directly. The bulk of commercially available PET-MR systems are quite large and expensive and mostly used on humans rather than for preclinical animal studies. This has led to a gap of knowledge in PET-MR imaging of small animal models used in preclinical research. Our work takes advantage of a new imaging system developed by Cubresa called 'NuPET'. This device is a MR-compatible PET scanner placed around the subject while they are within the toroidal bore of a MR scanner. With this equipment we are attempting to demonstrate the selective activation of serotonergic neurons in living rodent brains. To specify which neurons are to be activated, we use Designed Receptors Exclusively Activated by Designer Drug (DREADD) technology. These DREADDs are designer G-protein-coupled receptors. Neurons at the site of a stereotactic injection are transfected with a viral vector containing the proteins necessary to force expression of DREADDs in genetically modified rats. These may then be activated by administering the designer drug clozapine-N-oxide (CNO). This technique allows for precise spatiotemporal control of receptor signaling in vivo. Over two experiments (N=5, N=2) we have attempted to image the effect of DREADDs-mediated excitation of 5-HT neurons in rats. Voxel-based analysis of the data thus far show no confirmed statistically significant differences between rats given saline and those given CNO. Numerous methodological issues have been discovered within the experimental design, and are being addressed for a new trial of the technique and technology.

The authors wish to acknowledge funding from NSERC partnership grants, Mitacs, Cubresa, and Research Manitoba.

Multi-modal PET-MR imaging of the selective activation of serotonergic neurons in living rodent brains with DREADD technology

Multiquark states have been of great interest among hadronic physicists, and despite the big breakthrough that came in 2003 with the discovery of the charmonium-like tetraquark candidate X(3872), their internal quark structure (e.g., molecular versus diquark clusters) are not well-understood yet. QCD sum-rule mass estimates for multiquark states can provide insights on possible internal quark structures. Previous research suggests that the next-to-leading order (NLO) corrections to QCD sum-rule mass determinations are quite different in heavy and light multiquark states. 
The study of these multiquark systems can give us another approach to understand strong interactions at the elementary level and at different energy scales. The goal of this research is a detailed examination of the NLO corrections to mass estimates of the light scalar tetraquarks using QCD sum-rules.

NLO effects on light tetraquark mass estimates using QCD sum rules

We present some analytic results that describe the gluon field, or glasma, that exists at very early times after a collision of relativistic heavy ions at proper time $\tau=0$. We use a Colour Glass Condensate approach, and perform an expansion in $\tau$. We show that the expansion to order $\tau^6$ can be trusted to about $\tau=0.05$ fm/c. We calculate the transverse and longitudinal pressures and show that for $\tau < 0.05$ fm/c they move towards their equilibrium values of one third of the energy density. We study the spatial eccentricity of the plasma, and the Fourier coefficients of the azimuthal momentum distribution. Our results for the Fourier coefficients are larger than  expected, which contradicts the usual assumption that anisotropy is mostly generated during the hydrodynamic evolution of the plasma. We  find a significant correlation between the elliptic flow coefficient and the eccentricity, which indicates that the spatial inhomogeneity introduced by the initial geometry is effectively transmitted to the azimuthal distribution of the gluon momentum field, even at very early times. This result is interesting because correlations of this kind are  characteristic of the onset of hydrodynamic behaviour. We also calculate the angular momentum of the glasma and obtain results that are many orders of magnitude smaller than the initial angular momentum of two ions colliding with non-zero impact parameter. This indicates that most of the angular momentum carried by the valence quarks is not transmitted to the glasma. The result is significant because it contradicts the picture of a rapidly rotating initial glasma state,  but agrees with the current lack of experimental evidence for a global polarization effect in the hyperons and vector mesons produced in heavy ion collisions.

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