Room temperature "optical nanodiamond hyperpolarizer": Physics, design, and operation.

Dynamic Nuclear Polarization (DNP) is a powerful suite of techniques that deliver multifold signal enhancements in nuclear magnetic resonance (NMR) and MRI. The generated athermal spin states can also be exploited for quantum sensing and as probes for many-body physics. Typical DNP methods require the use of cryogens, large magnetic fields, and high power microwave excitation, which are expensive and unwieldy. Nanodiamond particles, rich in Nitrogen-Vacancy (NV) centers, have attracted attention as alternative DNP agents because they can potentially be optically hyperpolarized at room temperature. Here, unraveling new physics underlying an optical DNP mechanism first introduced by Ajoy et al. [Sci. Adv. 4, eaar5492 (2018)], we report the realization of a miniature "optical nanodiamond hyperpolarizer," where 13C nuclei within the diamond particles are hyperpolarized via the NV centers. The device occupies a compact footprint and operates at room temperature. Instrumental requirements are very modest: low polarizing fields, low optical and microwave irradiation powers, and convenient frequency ranges that enable miniaturization. We obtain the best reported optical 13C hyperpolarization in diamond particles exceeding 720 times of the thermal 7 T value (0.86% bulk polarization), corresponding to a ten-million-fold gain in averaging time to detect them by NMR. In addition, the hyperpolarization signal can be background-suppressed by over two-orders of magnitude, retained for multiple-minute long periods at low fields, and deployed efficiently even to 13C enriched particles. Besides applications in quantum sensing and bright-contrast MRI imaging, this work opens possibilities for low-cost room-temperature DNP platforms that relay the 13C polarization to liquids in contact with the high surface-area particles

Enhanced Optical 13C Hyperpolarization in Diamond Treated by High-Temperature Rapid Thermal Annealing

Methods of optical dynamic nuclear polarization open the door to the replenishable hyperpolarization of nuclear spins, boosting their nuclear magnetic resonance/imaging signatures by orders of magnitude. Nanodiamond powder rich in negatively charged nitrogen vacancy defect centers has recently emerged as one such promising platform, wherein 13C nuclei can be hyperpolarized through the optically pumped defects completely at room temperature. Given the compelling possibility of relaying this 13C polarization to nuclei in external liquids, there is an urgent need for the engineered production of highly “hyperpolarizable” diamond particles. Here, a systematic study of various material dimensions affecting optical 13C hyperpolarization in diamond particles is reported on. It is discovered surprisingly that diamond annealing at elevated temperatures ∼1720 °C has remarkable effects on the hyperpolarization levels enhancing them by above an order of magnitude over materials annealed through conventional means. It is demonstrated these gains arise from a simultaneous improvement in NV− electron relaxation/coherence times, as well as the reduction of paramagnetic content, and an increase in 13C relaxation lifetimes. This work suggests methods for the guided materials production of fluorescent, 13C hyperpolarized, nanodiamonds and pathways for their use as multimodal (optical and magnetic resonance) imaging and hyperpolarization agents

Oncological Outcome of Primary versus Secondary Muscle-Invasive Bladder Cancer Is Comparable after Radical Cystectomy

Background: High-risk non-muscle-invasive bladder cancer (NMIBC) progressing to muscle-invasive bladder cancer (MIBC) is associated with adverse tumour biology. It is unclear, however, whether outcome of NMIBC progressing to MIBC is adverse compared to primary MIBC and whether NMIBC of higher risk of progression to MIBC is adverse compared to NMIBC of lower risk. Objective: Our objective was to assess cancer-specific survival (CSS) following radical cystectomy (RC) for primary MIBC and for NMIBC progressing to MIBC in dependence of EORTC risk score. Materials and Methods: Clinical and histopathological characteristics and CSS of 150 patients were assessed. Secondary MIBCs were stratified by EORTC risk score at the last transurethral resection of bladder tumour for NMIBC. Results: CSS did not differ significantly between primary and secondary MIBC (p = 0.521). Secondary MIBC with high EORTC score had significantly shorter CSS compared to secondary MIBC with intermediate EORTC score (p = 0.029). In multivariable analysis, pathological tumour stage (HR = 3.77; p = 0.020) and lymph node stage (HR = 2.34; p = 0.022) were significantly correlated with CSS. Conclusion: While the outcome of secondary MIBC is not generally adverse compared to primary MIBC, the EORTC risk score not only reflects high risk of progression of NMIBC to MIBC, but also worse outcome following RC for secondary MIBC. Timely RC should thus be debated in high-risk NMIBC

The Charlson Comorbidity Index Predicts Survival after Disease Recurrence in Patients following Radical Cystectomy for Urothelial Carcinoma of the Bladder

Objective: To identify prognostic clinical and histopathological parameters, including comorbidity indices at the time of radical cystectomy (RC), for overall survival (OS) after recurrence following RC for urothelial carcinoma of the bladder (UCB). Materials and Methods: A retrospective multicenter study was carried out in 555 unselected consecutive patients who underwent RC with pelvic lymph node dissection for UCB from 2000 to 2010. A total of 227 patients with recurrence comprised our study group. Cox proportional hazards regression models were calculated with established variables to assess their independent influence on OS after recurrence. Results: The median time from RC to recurrence and the median OS after recurrence was 10.9 and 5.4 months, respectively. Neither the time to recurrence nor the type of recurrence (systematic vs. local) was predictive of the OS. In contrast, age (hazard ratio (HR) 1.53, p = 0.011), lymph node metastasis (HR 1.56, p = 0.007), and positive surgical margins (HR 1.53, p = 0.046) significantly affected the OS after disease recurrence. In addition, the dichotomized Charlson comorbidity index (CCI; dichotomized into >2 vs. 0-2) was the only comorbidity score with an independent prediction of OS (HR 1.41, p = 0.033). We observed a significant gain in the base model's predictive accuracy, i.e. from 68.4 to 70.3% (p < 0.001), after inclusion of the dichotomized CCI. Conclusions: We present the first outcome study of comorbidity indices used as predictors of OS after disease recurrence in patients undergoing RC for UCB. The CCI at the time of RC had no significant influence on the time to recurrence but represented an independent predictor of OS after disease recurrence

NH4+-stimulated and -inhibited components of K+ transport in rice (Oryza sativa L.)

The disruption of K+ transport and accumulation is symptomatic of NH4+ toxicity in plants. In this study, the influence of K+ supply (0.02–40 mM) and nitrogen source (10 mM NH4+ or NO3–) on root plasma membrane K+ fluxes and cytosolic K+ pools, plant growth, and whole-plant K+ distribution in the NH4+-tolerant plant species rice (Oryza sativa L.) was examined. Using the radiotracer 42K+, tissue mineral analysis, and growth data, it is shown that rice is affected by NH4+ toxicity under high-affinity K+ transport conditions. Substantial recovery of growth was seen as [K+]ext was increased from 0.02 mM to 0.1 mM, and, at 1.5 mM, growth was superior on NH4+. Growth recovery at these concentrations was accompanied by greater influx of K+ into root cells, translocation of K+ to the shoot, and tissue K+. Elevating the K+ supply also resulted in a significant reduction of NH4+ influx, as measured by 13N radiotracing. In the low-affinity K+ transport range, NH4+ stimulated K+ influx relative to NO3– controls. It is concluded that rice, despite its well-known tolerance to NH4+, nevertheless displays considerable growth suppression and disruption of K+ homeostasis under this N regime at low [K+]ext, but displays efficient recovery from NH4+ inhibition, and indeed a stimulation of K+ acquisition, when [K+]ext is increased in the presence of NH4+

AtHKT1;1 Mediates Nernstian Sodium Channel Transport Properties in Arabidopsis Root Stelar Cells

The Arabidopsis AtHKT1;1 protein was identified as a sodium (Na+) transporter by heterologous expression in Xenopus laevis oocytes and Saccharomyces cerevisiae. However, direct comparative in vivo electrophysiological analyses of a plant HKT transporter in wild-type and hkt loss-of-function mutants has not yet been reported and it has been recently argued that heterologous expression systems may alter properties of plant transporters, including HKT transporters. In this report, we analyze several key functions of AtHKT1;1-mediated ion currents in their native root stelar cells, including Na+ and K+ conductances, AtHKT1;1-mediated outward currents, and shifts in reversal potentials in the presence of defined intracellular and extracellular salt concentrations. Enhancer trap Arabidopsis plants with GFP-labeled root stelar cells were used to investigate AtHKT1;1-dependent ion transport properties using patch clamp electrophysiology in wild-type and athkt1;1 mutant plants. AtHKT1;1-dependent currents were carried by sodium ions and these currents were not observed in athkt1;1 mutant stelar cells. However, K+ currents in wild-type and athkt1;1 root stelar cell protoplasts were indistinguishable correlating with the Na+ over K+ selectivity of AtHKT1;1-mediated transport. Moreover, AtHKT1;1-mediated currents did not show a strong voltage dependence in vivo. Unexpectedly, removal of extracellular Na+ caused a reduction in AtHKT1;1-mediated outward currents in Columbia root stelar cells and Xenopus oocytes, indicating a role for external Na+ in regulation of AtHKT1;1 activity. Shifting the NaCl gradient in root stelar cells showed a Nernstian shift in the reversal potential providing biophysical evidence for the model that AtHKT1;1 mediates passive Na+ channel transport properties