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Glassing matrix deuteration could be a beneficial sample preparation method for 13C dynamic nuclear polarization (DNP) when large electron paramagnetic resonance (EPR) width free radicals are used. However, it could yield the opposite DNP effect when samples are doped with small EPR width free radicals. Herein, we have investigated the influence of solvent deuteration on the 13C nuclear and electron relaxation that go along with the effects on 13C DNP intensities at 3.35 T and 1.2 K. For 13C DNP samples doped with trityl OX063, the 13C DNP signals decreased significantly when the protons are replaced by deuterons in glycerol:water or DMSO:water solvents. Meanwhile, the corresponding solid-state 13C T1 relaxation times of trityl OX063-doped samples generally increased upon solvent deuteration. On the other hand, 13C DNP signals improved by a factor of ∼1.5 to 2 upon solvent deuteration of samples doped with 4-oxo-TEMPO. Despite this 13C DNP increase, there were no significant differences recorded in 13C T1 values of TEMPO-doped samples with nondeuterated or fully deuterated glassing matrices. While solvent deuteration appears to have a negligible effect on the electron T1 relaxation of both free radicals, the electron T2 relaxation times of these two free radicals generally increased upon solvent deuteration. These overall results suggest that while the solid-phase 13C DNP signals are dependent upon the changes in total nuclear Zeeman heat capacity, the 13C relaxation effects are related to 2H/1H nuclear spin diffusion-assisted 13C polarization leakage in addition to the dominant paramagnetic relaxation contribution of free radical centers. [ABSTRACT FROM AUTHOR]

Introduction: Venous varices are vascular lesions caused by vasodilatation. These oral cavity lesions are usually seen as papules or dark blue nodules on the tongue's ventral surface buccal and retro-commissural mucosae. They are generally asymptomatic but may cause problems such as bleeding on trauma or lack of esthetics. Although many treatment modalities exist for these lesions, the laser is a novel and less invasive method. It secures patient satisfaction more than other methods due to the lack of bleeding and pain. Unlike previous laser therapy methods used for cutting and excision of small vascular lesions, in this lesson, the coagulation properties of laser are employed to eliminate the lesion. Case Presentation: To illustrate, a 70-year-old female person was admitted to the dental clinic of the Semnan University of Medical Sciences, Iran, for a dental examination. She has no systemic problems. During the extra-oral examination, the lesion was visualized on the right side of her lower lip, and the initial diagnosis of a venous lake was made. The lesion was asymptomatic and had been present for several years. Likewise, after obtaining informed consent, treatment with a 940-diode laser was performed. Immediately after the irradiation, the lesion disappeared, and after four weeks, the lip's texture was completely normal. Conclusions: Exploiting the coagulation properties of the laser to eliminate venous lakes is advantageous over other methods because of the lack of bleeding or pain. Furthermore, this method has a shorter healing time. [ABSTRACT FROM AUTHOR]

Dynamic nuclear polarization (DNP) is a technique that uses a microwave-driven transfer of high spin alignment from electrons to nuclear spins. This is most effective at low temperature and high magnetic field, and with the invention of the dissolution method, the amplified nuclear magnetic resonance (NMR) signals in the frozen state in DNP can be harnessed in the liquid-state at physiologically acceptable temperature for in vitro and in vivo metabolic studies. A current optimization practice in dissolution DNP is to dope the sample with trace amounts of lanthanides such as Gd3+ or Ho3+, which further improves the polarization. While Gd3+ and Ho3+ have been optimized for use in dissolution DNP, other lanthanides have not been exhaustively studied for use in 13C DNP applications. In this work, two additional lanthanides with relatively high magnetic moments, Dy3+ and Tb3+, were extensively optimized and tested as doping additives for 13C DNP at 3.35 T and 1.2 K. We have found that both of these lanthanides are also beneficial additives, to a varying degree, for 13C DNP. The optimal concentrations of Dy3+ (1.5 mM) and Tb3+ (0.25 mM) for 13C DNP were found to be less than that of Gd3+ (2 mM). W-band electron paramagnetic resonance shows that these enhancements due to Dy3+ and Tb3+ doping are accompanied by shortening of electron T1 of trityl OX063 free radical. Furthermore, when dissolutionwas employed, Tb3+-doped samples were found to have similar liquid-state 13C NMRsignal enhancements compared to samples doped with Gd3+, and both Tb3+ and Dy3+ had a negligible liquid-state nuclear T1 shortening effect which contrasts with the significant reduction in T1 when using Gd3+. Our results showthat Dy3+ doping and Tb3+ doping have a beneficial impact on 13C DNP both in the solid and liquid states, and that Tb3+ in particular could be used as a potential alternative to Gd3+ in 13C dissolution DNP experiments. [ABSTRACT FROM AUTHOR]

Persian poetry in the 2000s, like many literary and artistic texts, has hidden meaning and reason the enjoyment of discovery of which is met by the criticism process method. One of the methods of studying poems of this decade is to look at the mutual contradictions, which indicate some parts of meaning, because if a poet accepts the historical evaluation of contradictions, he shows his alignment with classic beliefs and if he criticizes it, he represents the intellectual and cultural changes in personal or social level. In analysis of text contradictions, one of the items to be studied is the type of relation that the author or poet connects between two sides of contradiction, and in this case, poets in the 2000s indicated many intellectual infrastructures and type of evaluations changed to them. Among 20 poets studied in this research, 7 poets (Sare Dastaran, Majid Rafati, Garous Abdolmalekian, Abbas Saffari, Sara Mohammadi Ardehali, Shahab Mogharrabin, and Hafez Mousavi) obviously introduced invalid the goodness and badness of two sides of contradiction; i.e. the positive and negative aspects or vice and virtue of parties to the contradiction. The research findings show that the poets in the 2000s make doubt on the known and general contradictions, and also include in their works the new visual fields suitable to the language and time for invalidating the vice and virtue aspects of contradictions. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes is a common syndrome characterized by a steady rise in blood glucose levels and has various side effects, including oral complications such as periodontitis and dry mouth. Material and Methods: This case-control study was performed on 30 patients with type 2 diabetes mellitus and 30 normal people who were referred to Kowsar Hospital of Semnan, Iran. The study groups were evaluated for HbA1C, and unstimulated saliva and data were statistically analyzed. Results: Unstimulated saliva in diabetic patients was 0.02 ± 0.07 ml/min and ± 14.0 ± 02.0 ml in the control group (P <0.001). In the diabetic group, 18 out of the 30 diabetic patients (60%) had uncontrolled glucose (HbA1c was 7% or higher), and the rest had controlled glucose. According to the HbA1c study, the mean standard deviation of unstimulated saliva in controlled diabetic patients was 0.08 0 ± 0.02 ml/min and 0.06 ± 0.02 ml/min in uncontrolled patients, which showed a significant difference (p=0.006). Conclusion: Dry mouth was more prevalent in people with uncontrolled diabetes, so blood glucose level and its control had a significant effect on the reduction of unstimulated salivation. [ABSTRACT FROM AUTHOR]

The membrane proximal external region (MPER) of HIV-1 envelope glycoprotein (gp) 41 is an attractive vaccine target for elicitation of broadly neutralizing antibodies (bNAbs) by vaccination. However, current details regarding the quaternary structural organization of the MPER within the native prefusion trimer [(gp120/41)3] are elusive and even contradictory, hindering rational MPER immunogen design. To better understand the structural topology of the MPER on the lipid bilayer, the adjacent transmembrane domain (TMD) was appended (MPER-TMD) and studied. Membrane insertion of the MPER-TMD was sensitive both to the TMD sequence and cytoplasmic residues. Antigen binding of MPER-specific bNAbs, in particular 10E8 and DH511.2_K3, was significantly impacted by the presence of the TMD. Furthermore, MPER-TMD assembly into 10-nm diameter nanodiscs revealed a heterogeneous membrane array comprised largely of monomers and dimers, as enumerated by bNAb Fab binding using single-particle electron microscopy analysis, arguing against preferential trimeric association of native MPER and TMD protein segments. Moreover, introduction of isoleucine mutations in the C-terminal heptad repeat to induce an extended MPER α-helical bundle structure yielded an antigenicity profile of cell surface-arrayed Env variants inconsistent with that found in the native prefusion state. In line with these observations, electron paramagnetic resonance analysis suggested that 10E8 inhibits viral membrane fusion by lifting the MPER N-terminal region out of the viralmembrane, mandating the exposure of residues that would be occluded by MPER trimerization. Collectively, our data suggest that the MPER is not a stable trimer, but rather a dynamic segment adapted for structural changes accompanying fusion. [ABSTRACT FROM AUTHOR]

Glassing matrix deuteration could be a beneficial sample preparation method for 13 C dynamic nuclear polarization (DNP) when large electron paramagnetic resonance (EPR) width free radicals are used. However, it could yield the opposite DNP effect when samples are doped with small EPR width free radicals. Herein, we have investigated the influence of solvent deuteration on the 13 C nuclear and electron relaxation that go along with the effects on 13 C DNP intensities at 3.35 T and 1.2 K. For 13 C DNP samples doped with trityl OX063, the 13 C DNP signals decreased significantly when the protons are replaced by deuterons in glycerol:water or DMSO:water solvents. Meanwhile, the corresponding solid-state 13 C T 1 relaxation times of trityl OX063-doped samples generally increased upon solvent deuteration. On the other hand, 13 C DNP signals improved by a factor of ∼1.5 to 2 upon solvent deuteration of samples doped with 4-oxo-TEMPO. Despite this 13 C DNP increase, there were no significant differences recorded in 13 C T 1 values of TEMPO-doped samples with nondeuterated or fully deuterated glassing matrices. While solvent deuteration appears to have a negligible effect on the electron T 1 relaxation of both free radicals, the electron T 2 relaxation times of these two free radicals generally increased upon solvent deuteration. These overall results suggest that while the solid-phase 13 C DNP signals are dependent upon the changes in total nuclear Zeeman heat capacity, the 13 C relaxation effects are related to 2 H/ 1 H nuclear spin diffusion-assisted 13 C polarization leakage in addition to the dominant paramagnetic relaxation contribution of free radical centers.

Optimal efficiency of dissolution dynamic nuclear polarization (DNP) is essential to provide the required high sensitivity enhancements for in vitro and in vivo hyperpolarized 13 C nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI). At the nexus of the DNP process are the free electrons, which provide the high spin alignment that is transferred to the nuclear spins. Without changing DNP instrumental conditions, one way to improve 13 C DNP efficiency is by adding trace amounts of paramagnetic additives such as lanthanide (e.g., Gd 3+ , Ho 3+ , Dy 3+ , Tb 3+ ) complexes to the DNP sample, which has been observed to increase solid-state 13 C DNP signals by 100-250%. Herein, we have investigated the effects of paramagnetic transition metal complex R-NOTA (R = Mn 2+ , Cu 2+ , Co 2+ ) doping on the efficiency of 13 C DNP using trityl OX063 as the polarizing agent. Our DNP results at 3.35 T and 1.2 K show that doping the 13 C sample with 3 mM Mn 2+ -NOTA led to a substantial improvement of the solid-state 13 C DNP signal by a factor of nearly 3. However, the other transition metal complexes Cu 2+ -NOTA and Co 2+ -NOTA complexes, despite their paramagnetic nature, had essentially no impact on solid-state 13 C DNP enhancement. W-band electron paramagnetic resonance (EPR) measurements reveal that the trityl OX063 electron T 1 was significantly reduced in Mn 2+ -doped samples but not in Cu 2+ - and Co 2+ -doped DNP samples. This work demonstrates, for the first time, that not all paramagnetic additives are beneficial to DNP. In particular, our work provides a direct evidence that electron T 1 reduction of the polarizing agent by a paramagnetic additive is an essential requirement for the improvement seen in solid-state 13 C DNP signal.

Attainment of high NMR signal enhancements is crucial to the success of in vitro or in vivo hyperpolarized NMR or imaging (MRI) experiments. In this work, we report on the use of a superparamagnetic iron oxide nanoparticle (SPION) MRI contrast agent Feraheme (ferumoxytol) as a beneficial additive in 13 C samples for dissolution dynamic nuclear polarization (DNP). Our DNP data at 3.35 T and 1.2 K reveal that addition of 11 mM elemental iron concentration of Feraheme in trityl OX063-doped 3 M [1- 13 C] acetate samples resulted in a substantial improvement of 13 C DNP signal by a factor of almost 3-fold. Concomitant with the large DNP signal increase is the narrowing of the 13 C microwave DNP spectra for samples doped with SPION. W-band electron paramagnetic resonance (EPR) spectroscopy data suggest that these two prominent effects of SPION doping on 13 C DNP can be ascribed to the shortening of trityl OX063 electron T 1 as explained within the thermal mixing DNP model. Liquid-state 13 C NMR signal enhancements as high as 20,000-fold for SPION-doped samples were recorded after dissolution at 9.4 T and 297 K, which is about 3 times the liquid-state NMR signal enhancement of the control sample. While the presence of SPION in hyperpolarized solution drastically reduces 13 C T 1 , this can be mitigated by polarizing smaller aliquots of DNP samples. Moreover, we have shown that Feraheme nanoparticles (~30 nm in size) can be easily and effectively removed from the hyperpolarized liquid by simple mechanical filtration, thus one can potentially incorporate an in-line filtration for these SPIONS along the dissolution pathway of the hyperpolarizer-a significant advantage over other DNP enhancers such as the lanthanide complexes. The overall results suggest that the commercially-available and FDA-approved Feraheme is a highly efficient DNP enhancer that could be readily translated for use in clinical applications of dissolution DNP., Competing Interests: Notes The authors declare no competing financial interest.

Dissolution dynamic nuclear polarization (DNP) is one of the most successful techniques that resolves the insensitivity problem in liquid-state nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) by amplifying the signal by several thousand-fold. One way to further improve the DNP signal is the inclusion of trace amounts of lanthanides in DNP samples doped with trityl OX063 free radical as the polarizing agent. In practice, stable monomeric gadolinium complexes such as Gd-DOTA or Gd-HP-DO3A are used as beneficial additives in DNP samples, further boosting the DNP-enhanced solid-state 13 C polarization by a factor of 2 or 3. Herein, we report on the use of a trimeric gadolinium complex as a dopant in 13 C DNP samples to improve the 13 C DNP signals in the solid-state at 3.35 T and 1.2 K and consequently, in the liquid-state at 9.4 T and 298 K after dissolution. Our results have shown that doping the 13 C DNP sample with a complex which holds three Gd 3+ ions led to an improvement of DNP-enhanced 13 C polarization by a factor of 3.4 in the solid-state, on par with those achieved using monomeric Gd 3+ complexes but only requires about one-fifth of the concentration. Upon dissolution, liquid-state 13 C NMR signal enhancements close to 20 000-fold, approximately 3-fold the enhancement of the control samples, were recorded in the nearby 9.4 T high resolution NMR magnet at room temperature. Comparable reduction of 13 C spin-lattice T 1 relaxation time was observed in the liquid-state after dissolution for both the monomeric and trimeric Gd 3+ complexes. Moreover, W-band electron paramagnetic resonance (EPR) data have revealed that 3-Gd doping significantly reduces the electron T 1 of the trityl OX063 free radical, but produces negligible changes in the EPR spectrum, reminiscent of the results with monomeric Gd 3+ -complex doping. Our data suggest that the trimeric Gd 3+ complex is a highly beneficial additive in 13 C DNP samples and that its effect on DNP efficiency can be described in the context of the thermal mixing mechanism.

Dynamic nuclear polarization (DNP) is a technique that uses a microwave-driven transfer of high spin alignment from electrons to nuclear spins. This is most effective at low temperature and high magnetic field, and with the invention of the dissolution method, the amplified nuclear magnetic resonance (NMR) signals in the frozen state in DNP can be harnessed in the liquid-state at physiologically acceptable temperature for in vitro and in vivo metabolic studies. A current optimization practice in dissolution DNP is to dope the sample with trace amounts of lanthanides such as Gd 3+ or Ho 3+ , which further improves the polarization. While Gd 3+ and Ho 3+ have been optimized for use in dissolution DNP, other lanthanides have not been exhaustively studied for use in C13 DNP applications. In this work, two additional lanthanides with relatively high magnetic moments, Dy 3+ and Tb 3+ , were extensively optimized and tested as doping additives for C13 DNP at 3.35 T and 1.2 K. We have found that both of these lanthanides are also beneficial additives, to a varying degree, for C13 DNP. The optimal concentrations of Dy 3+ (1.5 mM) and Tb 3+ (0.25 mM) for C13 DNP were found to be less than that of Gd 3+ (2 mM). W-band electron paramagnetic resonance shows that these enhancements due to Dy 3+ and Tb 3+ doping are accompanied by shortening of electron T 1 of trityl OX063 free radical. Furthermore, when dissolution was employed, Tb 3+ -doped samples were found to have similar liquid-state C13 NMR signal enhancements compared to samples doped with Gd 3+ , and both Tb 3+ and Dy 3+ had a negligible liquid-state nuclear T 1 shortening effect which contrasts with the significant reduction in T 1 when using Gd 3+ . Our results show that Dy 3+ doping and Tb 3+ doping have a beneficial impact on C13 DNP both in the solid and liquid states, and that Tb 3+ in particular could be used as a potential alternative to Gd 3+ in C13 dissolution DNP experiments.