Technical note: Investigating the suitability of existing facilities for a new Lu-177 prostate-specific membrane antigen therapy program.

BACKGROUND: 177 Lu prostate-specific membrane antigen (PSMA) therapy prolongs survival for some prostate cancer patients. To adopt this technique, institutions may need to evaluate the suitability of existing infrastructure. PURPOSE: Develop a methodology to determine whether existing facilities can accommodate a 177 Lu-PSMA therapy program. METHODS: Room suitability is defined by both the ability to accommodate 177 Lu-PSMA therapy workflow and to provide appropriate radiation shielding. Two methods of shielding calculation were performed: (1) National Council on Radiation Protection and Measurements report 151 (NCRP-151), with workload defined in terms of the activity of 177 Lu administered, and (2) using the RadPro shielding calculator. This methodology was applied to 131 I therapy, PET-CT uptake, PET-SPECT injection, and orthovoltage therapy rooms. RESULTS: 131 I therapy rooms were found to meet both shielding and workflow requirements. The shielding was found to be adequate for orthovoltage and PET-SPECT facilities, neglecting patient transit between external washrooms. The workflow was the limiting factor for these rooms due to the requirement of dedicated washrooms that shield the patient and contain possible contamination. The PET-CT facility did not meet either criteria. The NCRP-151 method generally predicted a higher dose rate on the other side of shielding than did the RadPro calculator. The dose rate on the other side of concrete shielding as predicted by the NCRP-151 method increased relative to the dose rate predicted by the RadPro calculator as shielding thickness increased. For lead shielding, the dose rate predicted by the NCRP-151 method decreased relative to the result predicted by the RadPro calculator with increasing material thickness. CONCLUSIONS: 131 I therapy, PET-CT uptake, PET-SPECT injection, and orthovoltage therapy rooms were considered. The 131 I treatment rooms were the best candidate for 177 Lu-PSMA therapy, due to their shielding and capability to accommodate the necessary workflow.

Microwave Quantum Link between Superconducting Circuits Housed in Spatially Separated Cryogenic Systems.

Superconducting circuits are a strong contender for realizing quantum computing systems and are also successfully used to study quantum optics and hybrid quantum systems. However, their cryogenic operation temperatures and the current lack of coherence-preserving microwave-to-optical conversion solutions have hindered the realization of superconducting quantum networks spanning different cryogenic systems or larger distances. Here, we report the successful operation of a cryogenic waveguide coherently linking transmon qubits located in two dilution refrigerators separated by a physical distance of five meters. We transfer qubit states and generate entanglement on demand with average transfer and target state fidelities of 85.8% and 79.5%, respectively, between the two nodes of this elementary network. Cryogenic microwave links provide an opportunity to scale up systems for quantum computing and create local area superconducting quantum communication networks over length scales of at least tens of meters.

Coherent microwave-photon-mediated coupling between a semiconductor and a superconducting qubit.

Semiconductor qubits rely on the control of charge and spin degrees of freedom of electrons or holes confined in quantum dots. They constitute a promising approach to quantum information processing, complementary to superconducting qubits. Here, we demonstrate coherent coupling between a superconducting transmon qubit and a semiconductor double quantum dot (DQD) charge qubit mediated by virtual microwave photon excitations in a tunable high-impedance SQUID array resonator acting as a quantum bus. The transmon-charge qubit coherent coupling rate (~21 MHz) exceeds the linewidth of both the transmon (~0.8 MHz) and the DQD charge qubit (~2.7 MHz). By tuning the qubits into resonance for a controlled amount of time, we observe coherent oscillations between the constituents of this hybrid quantum system. These results enable a new class of experiments exploring the use of two-qubit interactions mediated by microwave photons to create entangled states between semiconductor and superconducting qubits.

Nanowire Superinductance Fluxonium Qubit.

We characterize a fluxonium qubit consisting of a Josephson junction inductively shunted with a NbTiN nanowire superinductance. We explain the measured energy spectrum by means of a multimode theory accounting for the distributed nature of the superinductance and the effect of the circuit nonlinearity to all orders in the Josephson potential. Using multiphoton Raman spectroscopy, we address multiple fluxonium transitions, observe multilevel Autler-Townes splitting and measure an excited state lifetime of T_{1}=20 µs. By measuring T_{1} at different magnetic flux values, we find a crossover in the lifetime limiting mechanism from capacitive to inductive losses.

Fast and Unconditional All-Microwave Reset of a Superconducting Qubit.

Active qubit reset is a key operation in many quantum algorithms, and particularly in quantum error correction. Here, we experimentally demonstrate a reset scheme for a three-level transmon artificial atom coupled to a large bandwidth resonator. The reset protocol uses a microwave-induced interaction between the |f,0⟩ and |g,1⟩ states of the coupled transmon-resonator system, with |g⟩ and |f⟩ denoting the ground and second excited states of the transmon, and |0⟩ and |1⟩ the photon Fock states of the resonator. We characterize the reset process and demonstrate reinitialization of the transmon-resonator system to its ground state in less than 500 ns and with 0.2% residual excitation. Our protocol is of practical interest as it has no additional architectural requirements beyond those needed for fast and efficient single-shot readout of transmons, and does not require feedback.

Coherent spin-photon coupling using a resonant exchange qubit.

Electron spins hold great promise for quantum computation because of their long coherence times. Long-distance coherent coupling of spins is a crucial step towards quantum information processing with spin qubits. One approach to realizing interactions between distant spin qubits is to use photons as carriers of quantum information. Here we demonstrate strong coupling between single microwave photons in a niobium titanium nitride high-impedance resonator and a three-electron spin qubit (also known as a resonant exchange qubit) in a gallium arsenide device consisting of three quantum dots. We observe the vacuum Rabi mode splitting of the resonance of the resonator, which is a signature of strong coupling; specifically, we observe a coherent coupling strength of about 31 megahertz and a qubit decoherence rate of about 20 megahertz. We can tune the decoherence electrostatically to obtain a minimal decoherence rate of around 10 megahertz for a coupling strength of around 23 megahertz. We directly measure the dependence of the qubit-photon coupling strength on the tunable electric dipole moment of the qubit using the 'AC Stark' effect. Our demonstration of strong qubit-photon coupling for a three-electron spin qubit is an important step towards coherent long-distance coupling of spin qubits.

Deterministic quantum state transfer and remote entanglement using microwave photons.

Sharing information coherently between nodes of a quantum network is fundamental to distributed quantum information processing. In this scheme, the computation is divided into subroutines and performed on several smaller quantum registers that are connected by classical and quantum channels 1 . A direct quantum channel, which connects nodes deterministically rather than probabilistically, achieves larger entanglement rates between nodes and is advantageous for distributed fault-tolerant quantum computation 2 . Here we implement deterministic state-transfer and entanglement protocols between two superconducting qubits fabricated on separate chips. Superconducting circuits 3 constitute a universal quantum node 4 that is capable of sending, receiving, storing and processing quantum information5-8. Our implementation is based on an all-microwave cavity-assisted Raman process 9 , which entangles or transfers the qubit state of a transmon-type artificial atom 10 with a time-symmetric itinerant single photon. We transfer qubit states by absorbing these itinerant photons at the receiving node, with a probability of 98.1 ± 0.1 per cent, achieving a transfer-process fidelity of 80.02 ± 0.07 per cent for a protocol duration of only 180 nanoseconds. We also prepare remote entanglement on demand with a fidelity as high as 78.9 ± 0.1 per cent at a rate of 50 kilohertz. Our results are in excellent agreement with numerical simulations based on a master-equation description of the system. This deterministic protocol has the potential to be used for quantum computing distributed across different nodes of a cryogenic network.

Strong spin-photon coupling in silicon.

Long coherence times of single spins in silicon quantum dots make these systems highly attractive for quantum computation, but how to scale up spin qubit systems remains an open question. As a first step to address this issue, we demonstrate the strong coupling of a single electron spin and a single microwave photon. The electron spin is trapped in a silicon double quantum dot, and the microwave photon is stored in an on-chip high-impedance superconducting resonator. The electric field component of the cavity photon couples directly to the charge dipole of the electron in the double dot, and indirectly to the electron spin, through a strong local magnetic field gradient from a nearby micromagnet. Our results provide a route to realizing large networks of quantum dot-based spin qubit registers.

Combination of micellar casein with calcium and vitamins D2 and K2 improves bone status of ovariectomized mice.

UNLABELLED: Nutritional approaches may help to preserve bone quality. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) including micellar casein rich in calcium, vitamin D2 and vitamin K2, to improve bone mineral density. INTRODUCTION: The aim of postmenopausal osteoporosis treatment is to decrease bone resorption and/or increase bone formation. Because of the slow bone turnover, osteoporosis prevention and therapies are long-lasting, implying great costs and poor compliance. Even if the effects of nutrition on bone are not as marked as that of pharmaceutical agents, it can be of great help. The purpose of our study was to demonstrate the efficiency of an innovative bone health product (BHP) containing micellar casein rich in calcium, vitamin D2 and vitamin K2, for the improvement of bone mineral density (BMD). METHODS: An ovariectomized mice model was used to study the effect of different concentrations of the ingredient on BMD and microarchitectural parameters. Blood concentrations of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type 1 procollagene (PINP), alkaline phosphatase (ALP), osteocalcin (OC) and RANKL were also measured to evaluate bone remodelling, To evaluate the efficiency of the product to modulate osteoblast and osteoclast growth and differentiation, primary murine bone cells were used. RESULTS: In vivo studies showed that BMD and microarchitectural parameters were dose-dependently improved after ingestion of the supplement for 3 months. We also report increased osteoblast activity as shown by increased OC activity and decreased osteoclastogenesis as shown by reduced CTX activity. In vitro studies support that BHPs stimulate osteoblast differentiation and mineralization and inhibit osteoclast resorption activity. CONCLUSION: Our results show that, when chronically ingested, BHPs improve BMD of ovariectomized mice. This work supports that providing an ingredient including micellar casein rich in calcium, vitamin D2 and vitamin K2 is more efficient than the control diet to maintain bone quality.

Computer modelling integrated with micro-CT and material testing provides additional insight to evaluate bone treatments: Application to a beta-glycan derived whey protein mice model.

The primary aim of this study was to evaluate the influence of a whey protein diet on computationally predicted mechanical strength of murine bones in both trabecular and cortical regions of the femur. There was no significant influence on mechanical strength in cortical bone observed with increasing whey protein treatment, consistent with cortical tissue mineral density (TMD) and bone volume changes observed. Trabecular bone showed a significant decline in strength with increasing whey protein treatment when nanoindentation derived Young׳s moduli were used in the model. When microindentation, micro-CT phantom density or normalised Young׳s moduli were included in the model a non-significant decline in strength was exhibited. These results for trabecular bone were consistent with both trabecular bone mineral density (BMD) and micro-CT indices obtained independently. The secondary aim of this study was to characterise the influence of different sources of Young׳s moduli on computational prediction. This study aimed to quantify the predicted mechanical strength in 3D from these sources and evaluate if trends and conclusions remained consistent. For cortical bone, predicted mechanical strength behaviour was consistent across all sources of Young׳s moduli. There was no difference in treatment trend observed when Young׳s moduli were normalised. In contrast, trabecular strength due to whey protein treatment significantly reduced when material properties from nanoindentation were introduced. Other material property sources were not significant but emphasised the strength trend over normalised material properties. This shows strength at the trabecular level was attributed to both changes in bone architecture and material properties.

Tissue-specific targeting of cell fate regulatory genes by E2f factors.

Cell cycle proteins are important regulators of diverse cell fate decisions, and in this capacity have pivotal roles in neurogenesis and brain development. The mechanisms by which cell cycle regulation is integrated with cell fate control in the brain and other tissues are poorly understood, and an outstanding question is whether the cell cycle machinery regulates fate decisions directly or instead as a secondary consequence of proliferative control. Identification of the genes targeted by E2 promoter binding factor (E2f) transcription factors, effectors of the pRb/E2f cell cycle pathway, will provide essential insights into these mechanisms. We identified the promoter regions bound by three neurogenic E2f factors in neural precursor cells in a genome-wide manner. Through bioinformatic analyses and integration of published genomic data sets we uncovered hundreds of transcriptionally active E2f-bound promoters corresponding to genes that control cell fate processes, including key transcriptional regulators and members of the Notch, fibroblast growth factor, Wnt and Tgf-ß signaling pathways. We also demonstrate a striking enrichment of the CCCTC binding factor transcription factor (Ctcf) at E2f3-bound nervous system-related genes, suggesting a potential regulatory co-factor for E2f3 in controlling differentiation. Finally, we provide the first demonstration of extensive tissue specificity among E2f target genes in mammalian cells, whereby E2f3 promoter binding is well conserved between neural and muscle precursors at genes associated with cell cycle processes, but is tissue-specific at differentiation-associated genes. Our findings implicate the cell cycle pathway as a widespread regulator of cell fate genes, and suggest that E2f3 proteins control cell type-specific differentiation programs by regulating unique sets of target genes. This work significantly enhances our understanding of how the cell cycle machinery impacts cell fate and differentiation, and will importantly drive further discovery regarding the mechanisms of cell fate control and transcriptional regulation in the brain, as well as in other tissues.

Regulation of µ and δ opioid receptor functions: involvement of cyclin-dependent kinase 5.

BACKGROUND AND PURPOSE: Phosphorylation of δ opioid receptors (DOP receptors) by cyclin-dependent kinase 5 (CDK5) was shown to regulate the trafficking of this receptor. Therefore, we aimed to determine the role of CDK5 in regulating DOP receptors in rats treated with morphine or with complete Freund's adjuvant (CFA). As µ (MOP) and DOP receptors are known to be co-regulated, we also sought to determine if CDK5-mediated regulation of DOP receptors also affects MOP receptor functions. EXPERIMENTAL APPROACH: The role of CDK5 in regulating opioid receptors in CFA- and morphine-treated rats was studied using roscovitine as a CDK inhibitor and a cell-penetrant peptide mimicking the second intracellular loop of DOP receptors (C11-DOPri2). Opioid receptor functions were assessed in vivo in a series of behavioural experiments and correlated by measuring ERK1/2 activity in dorsal root ganglia homogenates. KEY RESULTS: Chronic roscovitine treatment reduced the antinociceptive and antihyperalgesic effects of deltorphin II (Dlt II) in morphine- and CFA-treated rats respectively. Repeated administrations of C11-DOPri2 also robustly decreased Dlt II-induced analgesia. Interestingly, DAMGO-induced analgesia was significantly increased by roscovitine and C11-DOPri2. Concomitantly, in roscovitine-treated rats the Dlt II-induced ERK1/2 activation was decreased, whereas the DAMGO-induced ERK1/2 activation was increased. An acute roscovitine treatment had no effect on Dlt II- or DAMGO-induced analgesia. CONCLUSIONS AND IMPLICATIONS: Together, our results demonstrate that CDK5 is a key player in the regulation of DOP receptors in morphine- and CFA-treated rats and that the regulation of DOP receptors by CDK5 is sufficient to modulate MOP receptor functions through an indirect process.

Low birth weight is associated with adiposity, impaired skeletal muscle energetics and weight loss resistance in mice.

BACKGROUND: In utero undernutrition is associated with obesity and insulin resistance, although its effects on skeletal muscle remain poorly defined. Therefore, in the current study we explored the effects of in utero food restriction on muscle energy metabolism in mice. METHODS: We used an experimental mouse model system of maternal undernutrition during late pregnancy to examine offspring from undernourished dams (U) and control offspring from ad libitum-fed dams (C). Weight loss of 10-week-old offspring on a 4-week 40% calorie-restricted diet was also followed. Experimental approaches included bioenergetic analyses in isolated mitochondria, intact (permeabilized) muscle and at the whole body level. RESULTS: U have increased adiposity and decreased glucose tolerance compared to C. Strikingly, when U are put on a 40% calorie-restricted diet they lose half as much weight as calorie-restricted controls. Mitochondria from muscle overall from U had decreased coupled (state 3) and uncoupled (state 4) respiration and increased maximal respiration compared to C. Mitochondrial yield was lower in U than C. In permeabilized fiber preparations from mixed fiber-type muscle, U had decreased mitochondrial content and decreased adenylate-free leak respiration, fatty acid oxidative capacity and state 3 respiratory capacity through complex I. Fiber maximal oxidative phosphorylation capacity did not differ between U and C but was decreased with calorie restriction. CONCLUSIONS: Our results reveal that in utero undernutrition alters metabolic physiology through a profound effect on skeletal muscle energetics and blunts response to a hypocaloric diet in adulthood. We propose that mitochondrial dysfunction links undernutrition in utero with metabolic disease in adulthood.

Quantum heating of a nonlinear resonator probed by a superconducting qubit.

We measure the quantum fluctuations of a pumped nonlinear resonator using a superconducting artificial atom as an in situ probe. The qubit excitation spectrum gives access to the frequency and amount of excitation of the intracavity field fluctuations, from which we infer its effective temperature. These quantities are found to be in agreement with theoretical predictions; in particular, we experimentally observe the phenomenon of quantum heating.

Measurement-induced qubit state mixing in circuit QED from up-converted dephasing noise.

We observe measurement-induced qubit state mixing in a transmon qubit dispersively coupled to a planar readout cavity. Our results indicate that dephasing noise at the qubit-readout detuning frequency is up-converted by readout photons to cause spurious qubit state transitions, thus limiting the nondemolition character of the readout. Furthermore, we use the qubit transition rate as a tool to extract an equivalent flux noise spectral density at f~1 GHz and find agreement with values extrapolated from a 1/f(α) fit to the measured flux noise spectral density below 1 Hz.

Dipole coupling of a double quantum dot to a microwave resonator.

We demonstrate the realization of a hybrid solid-state quantum device, in which a semiconductor double quantum dot is dipole coupled to the microwave field of a superconducting coplanar waveguide resonator. The double dot charge stability diagram extracted from measurements of the amplitude and phase of a microwave tone transmitted through the resonator is in good agreement with that obtained from transport measurements. Both the observed frequency shift and linewidth broadening of the resonator are explained considering the double dot as a charge qubit coupled with a strength of several tens of MHz to the resonator.

Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H/HeN mice.

SUMMARY: This study evaluates the effect of hydrolyzed collagen (HC) on bone health of ovariectomized mice (OVX) at different ages. Twenty-six weeks after the OVX procedure, HC ingestion was still able to improve significantly bone mineral density (BMD) and some femur biomechanical parameters. Moreover, HC ingestion for 1 month before surgery prevented BMD decrease. INTRODUCTION: HC can play an important role in preserving BMD before osteoporosis appears. The aim of this study was to evaluate the effect of HC on bone health of ovariectomized mice at different ages. METHODS: Female C3H mice were either OVX at 3 or 6 months and fed for 6 months (first experiment) or 3 months (second experiment) with diet including 0, 10, or 25 g/kg of HC. In the second experiment, one group received HC 1 month before surgery, and two groups received the supplementation immediately after surgery, one fed ad libitum and the other by gavage. Mice treated with raloxifene were used as a positive control. BMD, femur intrinsic and extrinsic biomechanical properties, and type I collagen C-terminal telopeptide were measured after 12 and 26 weeks. Food intake and spontaneous physical activity were also recorded. RESULTS: The OVX procedure increased body weight, while food intake decreased, thus suggesting that resting metabolism was decreased. Ingestion of 25 g/kg of HC for 3 or 6 months reduced bone loss significantly in, respectively, 3- and 6-month-old OVX mice. The lowest HC concentration was less efficient. HC ingestion for 3 months is as efficient as raloxifene to protect 3-month-old OVX mice from bone loss. Our results also demonstrated that HC ingestion before surgery prevented the BMD decreases. CONCLUSION: This study confirms that dietary collagen reduces bone loss in OVX mice by increasing the diameter of the cortical areas of femurs and can have a preventive effect.

Sci-Fri AM: Imaging - 01: Feasibility of estimating choline kinase activity with kinetic modeling of 18F-fluorocholine pet imaging of prostate cancer.

Prostate cancer (PCa) detection and delineation remains a challenge for medical imaging. Studies have shown 18 F-Fluorocholine (FCH) PET imaging to be a promising modality in the detection of recurrent PCa. Detection of denovo PCa is more challenging, as lesions such as benign prostatic hyperplasia (BPH) may adversely affect the sensitivity and specificity of the modality. PCa and BPH have been shown to exhibit similar uptake of FCH, yet it has been shown that phosphocholine levels are much more elevated in PCa compared to BPH. Therefore, it would be useful to measure the activity of phosphorylation via choline kinase (k3 ) in order to differentiate PCa from BPH. This work examines the feasibility of using a compartmental model to estimate k3 with dynamic 18 F-Fluorocholine PET imaging. JSim software [1] was used to simulate the compartmental model for FCH exchange. A simulated tissue curve was generated using predefined parameters and the model's ability to estimate these parameters through fitting of the simulated tissue curve with and without noise was investigated. The fitting procedure was performed using the non-negative least squares algorithm in MATLAB after the equation governing fitting was linearized. In the noiseless case, the model was able to accurately identify the values of each rate parameter. For the noisy case with an SNR of 10:1, the mean estimated k3 for 10,000 runs had a coefficient of variation of 14.9%. The kinetic model shows promise for quantifying k3 , which would allow the differentiation of malignant and benign tumours of the prostate.

Observation of resonant photon blockade at microwave frequencies using correlation function measurements.

Creating a train of single photons and monitoring its propagation and interaction is challenging in most physical systems, as photons generally interact very weakly with other systems. However, when confining microwave frequency photons in a transmission line resonator, effective photon-photon interactions can be mediated by qubits embedded in the resonator. Here, we observe the phenomenon of photon blockade through second-order correlation function measurements. The experiments clearly demonstrate antibunching in a continuously pumped source of single microwave photons measured by using microwave beam splitters, linear amplifiers, and quadrature amplitude detectors. We also investigate resonance fluorescence and Rayleigh scattering in Mollow-triplet-like spectra.