Reduced skin blood flow has been reported in neuropathic pain patients as well as various peripheral neuropathic pain model animals. We have previously shown that vasodilators, which improves reduced ...skin blood flow, correlatively alleviate neuropathic pain in chronic constriction injury (CCI) mice, a model of neuropathic pain from peripheral nerve injury. Here, we sought to elucidate the mechanism underlying the reduced skin blood flow in CCI rats. The skin blood flow of the ipsilateral plantar arteries was significantly reduced compared to that of the contralateral ones 4 weeks after loose ligation of the sciatic nerve. The contraction induced by noradrenaline, serotonin, and U46619, a thromboxane receptor agonist, in the isolated ipsilateral plantar arteries was significantly enhanced compared to that in the contralateral ones. KB-R7943, a Na+/Ca2+ exchanger (NCX) inhibitor, shifted the concentration-response curves of noradrenaline to the left in the contralateral arteries but had no effect on the ipsilateral side. There was no significant difference in concentration-response curves of noradrenaline between the ipsilateral and contralateral arteries in the presence of KB-R7943. Amiloride, a non-specific inhibitor of Na+ channels and transporters, comparably shifted concentration-response curves of noradrenaline to the left in both the contralateral and ipsilateral arteries. One hundred nM of noradrenaline induced intracellular Ca2+ elevation in the ipsilateral arteries, which was significantly larger than that induced by 300-nM noradrenaline in the contralateral arteries. These results suggest that reduced peripheral blood flow after nerve injury is due to Na+-dependent inactivation of NCX in the ipsilateral plantar arteries.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ferromagnetic resonance (FMR) was observed for Co82Pt12 films with various process. And relation between effective damping factor (
α
eff
) and compositional modulation (CM) in the atomic layers, and ...other magnetic properties to investigate the relationship between local variation of the magnetic properties and the
α
eff
. The CM was changed by the substrate temperature T
sub and deposition rate of the Co-Pt alloy film. As a result, it was found that 1) For the T
sub dependence,
α
eff
took maximum value of 0.22 at T
sub = 200 oC. 2) For the rate dependence, a
eff linearly increases with 0.12 to 0.35 with increasing deposition rate from 0.3 to 2.0 nm/sec. 3) There was no similar tendency between a
eff and CM for the Co-Pt alloy film with T
sub and rate change. Thus the CM is not dominant factor of the a
eff for the compositionally modulated Co-Pt alloy film.
Background
Precise imaging of nerves have been challenging in the head and neck region, mainly due to low spatial resolution. Here, we investigated how nerves in the head and neck region could be ...visualized using an ultra‐high magnetic field MR system.
Methods
We used formol‐carbol‐fixed human cadaveric necks and obtained MR diffusion tensor images (DTIs) using a 9.4 Tesla (T) ultra‐high magnetic field MR system. Afterward, we prepared tissue sections and checked the anatomic relationships between the neurons and the carotid artery in order to confirm that the visualized fibers are indeed neuron fibers.
Results
We were able to identify nerves, including the vagus nerve, the hypoglossal nerve, and the spinal‐accessory nerve. Hematoxylin‐eosin stained histological sections confirmed neuron fibers in the same anatomic position.
Conclusion
This technique has the feasibility to be applied for a more accurate anatomic understanding, maybe even close to a histological level.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Head and neck squamous cell carcinomas (HNSCC) are well suited for cancer vaccination strategies. In addition to tumor-associated antigens (TAAs) and endogenous retrovirus (ERV) encoded proteins, ...HNSCCs have a relatively high tumor mutational burden encoding potential neoepitopes. Peptide vaccine candidates are prioritized by predicted high-affinity to major histocompatibility complex (MHC) class I with MHC-II affinity largely not being considered. Herein, we extend previous studies to evaluate therapeutic vaccination in the mouse oral cancer (MOC) 22 model. Two distinct MOC22 derived SLPs were tested - a TSA-oriented mutant intercellular adhesion molecule 1 (mICAM1) and p15E, an ERV encoded antigen. In silico prediction revealed mICAM1 SLP bore strong MHC-I and MHC-II epitopes sharing a mutant residue with vaccination significantly increasing both antigen-specific IFN-γ producing CD4
+
and CD8
+
T cells. By contrast, p15E SLP had a predicted high-affinity MHC-I epitope but lacked an MHC-II epitope and vaccination induced antigen-specific CD8
+
but not CD4
+
T cell responses. Therapeutic mICAM1 vaccination attenuated tumor growth effectively with mICAM1-specific T cells displaying durable IFN-γ production compared with p15E SLP. Furthermore, mICAM1 SLPs carrying weakened MHC-II binding epitopes were unable to control tumor growth. These data underscore the potential value of therapeutic targeting of HNSCC epitopes and highlight the importance of studying distinct antigen classes in this setting. Moreover, they raise the possibility that, at least in part, CD4
+
T cell help is critical for cancer vaccination in this preclinical HNSCC model and suggest in silico prediction approaches prioritize overlapping MHC-I and MHC-II epitopes to generate potent cancer vaccines.
Background: Implantable cardiac monitor (ICM) is an effective tool to detect atrial fibrillation (AF) in patients withembolic stroke undetermined sources (ESUS). We investigated predictive factors ...for AF detection in ESUS patientswith ICM implantation. Methods: A total of 29 ESUS patients who underwent ICM implantation (median 71 66-84 years and 18 males)were followed-up for a median of 253 44-570 days. Results: AF was detected in 10 patients (34.5%). The median time from ICM implantation to AF detection was 41.533.25-59.25 days and that from stroke onset to AF detection was 62.5 52.25-71.75 days. AF was detected within90 days after ICM implantation in 90% (9/10) of the study patients. Plasma brain natriuretic peptide level wassignificantly higher in patients with AF detection than in those without it (125 49.8-550.8 versus 18.2 14.1-60.0 pg/mL, p=0.007). More frequent supraventricular premature contraction (SVPC) on Holter electrocardiogram (ECG)was observed in patients with AF detection than in those without it (1.81 0.40-4.80 versus 0.04 0.02-0.13 %/day,p<0.001). Cox proportional hazards model showed that the frequent SVPCs was a significant factor for AF detection. Conclusions: The frequent SVPCs on Holter ECG is an independent predictor for covert AF in ESUS patients.
We investigate the spin dynamics of a NiFe/SiN/GaAs nanohybrid structure, in which the volume of NiFe is significantly reduced by ion milling. The photogenerated GaAs electron spins induce the ...electron Larmor precession with a long decay component (LDC) with a time constant τLDC of 550 ps under zero field at room temperature, indicating the presence of an effective magnetic field. The LDC reflects the relaxation of NiFe magnetization, whose time constant is modulated by the inner product of NiFe magnetization and GaAs electron spins in the external field. These results indicate the existence of an exchange interaction between the NiFe magnetization and GaAs electron spins.
In drug discovery, the prediction of activity and absorption, distribution, metabolism, excretion, and toxicity parameters is one of the most important approaches in determining which compound to ...synthesize next. In recent years, prediction methods based on deep learning as well as non-deep learning approaches have been established, and a number of applications to drug discovery have been reported by various companies and organizations. In this research, we performed activity prediction using deep learning and non-deep learning methods on in-house assay data for several hundred kinases and compared and discussed the prediction results. We found that the prediction accuracy of the single-task graph neural network (GNN) model was generally lower than that of the non-deep learning model (LightGBM), but the multitask GNN model, which combined data from other kinases, comprehensively outperformed LightGBM. In addition, the extrapolative validity of the multitask model was verified by using it for prediction on known kinase ligands. We observed an overlap between characteristic protein–ligand interaction sites and the atoms that are important for prediction. By building appropriate models based on the conditions of the data set and analyzing the feature importance of the prediction results, a ligand-based prediction method may be used not only for activity prediction but also for drug design.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Aim
Cardiopulmonary resuscitation is vital for survival after cardiac arrest, and chest compressions are an important aspect of this. When performing chest compression in a hospital setting, the ...rescuer often has to kneel on the bed to overcome inconvenient differences in height between the rescuer and the bed. However, as yet no study has evaluated the quality of chest compressions in this position. The aim of this study was to examine the impact on the quality of chest compressions while kneeling on the bed.
Methods
Fifteen female students performed 2‐min chest compressions on a manikin placed on the floor and a bed. Measurement parameters included compression depth, heart rate, integrated electromyogram, and a visual analog scale. The parameters were measured every 30 s and were statistically compared between the conditions.
Results
Compression depth at 30, 60, 90, and 120 s differed significantly between the conditions. Heart rate values at 150 and 210 s of recovery significantly differed between the conditions. Integrated electromyogram values for the trapezius, rectus femoris, and biceps femoris differed between the floor and bed conditions during 2‐min chest compressions, whereas the external oblique muscle significantly differed at 60 and 120 s. Visual analog scales for fatigue, effectiveness, and stability significantly differed between the conditions.
Conclusion
Kneeling on the bed does not enable grounding of the toe, causing the upper body to be unstable and limiting generation of the power required for chest compression. Our results suggest that rotation every minute is necessary to maintain effective cardiopulmonary resuscitation while kneeling on the bed.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Thermally assisted recording system is a promising candidate to overcome the trilemma of perpendicular magnetic recording hard disk drive development. In this paper, we introduce our current research ...about evaluation for the media material. In-plane X-ray diffraction technique is effective to evaluate atomic layer stacking structure of (111)-oriented face-centered cubic, c-plane-oriented hexagonal closed packed (hcp), and their intermediate structure with stacking faults of CoPt alloy thin film. Analytical results of Co50Pt50-based thin film shows that changing the valence electron number closer to 9 can effectively reduce the stacking fault. In practical, perfect hcp atomic layer stacking can be achieved by substituting Pt (group 10) with Rh (group 9). High-angle annular dark field of scanning transmission electron microscopy with probe diameter of 1 Å can effectively observe composition modulated atomic layer stacking with the super-lattice diffraction in Co-based alloy films. In practical, for Co80M20 (M: Ir, Pt) thin film sputtered under high substrate temperature, the irregular or alternately layered structure of M rich and M poor layer can be observed directly. To evaluate Curie temperature (TC), which is an important physical property of thermally assisted media, conduction electron spin-dependent scattering should be the focus. Fitting dielectric spectra for MnSb thin film with TC ~ 320 ° C measured with the ellipsometry and analyzing the Drude's term, temperature dependence of resistivity and scattering time at around TC was confirmed.