melanocortin 1 receptor br Methods br Results Information


Information for the 45 patients, including gender, duration of transplantation and donor status, is provided in Table 1. There were statistically significant differences in GFR and duration of transplantation among the four groups (all p < 0.01). There was no significant difference in RI among the four groups (p = 0.997). The difference in corticomedullary strain was significant in all paired groups (all p < 0.005) (Fig. 4). However, the difference in inter-lobar artery RI was not significant in any paired group (all p > 0.05). There were no significant differences in EDV or PSV between groups 1 and 2 or between groups 3 and group 4 (p > 0.05) in the initial statistical analysis of the four groups. We combined groups 1 and 2 to form a new group with low-grade (≤25%) cortical IF/TA and groups 3 and 4 to form a new group with high-grade (>26%) cortical IF/TA, and then used two independent t-tests to examine the differences in EDV (Fig. 5) and PSV (Fig. 6) between the two new groups.
The differences in EDV and PSV between ≤25% and >26% renal cortical IF/TA were significantly significant (p < 0.001). An inverse correlation was found between corticomedullary strain and grade of cortical IF/TA (odds ratio = −6.097, 95% confidence interval: −9.119 to −3.075, p < 0.001) with the logistic ordinal regression test, whereas the correlation between cortical fibrosis and EDV (odds ratio = −0.203, 95% confidence interval: −0.699 to 0.294, p = 0.424) or PSV (odds ratio = 0.083, 95% confidence interval: −0.091 to 0.257, p = 0.351) was not significant. In addition, there was a moderate positive correlation between duration of transplantation and grade of renal allograft cortical IF/TA (r2 = 0.67, p = 0.00000045). Corticomedullary strain, EDV and PSV significantly differed between recipients with a GFR >60 and those melanocortin 1 receptor with a GFR <60 (all p < 0.001), whereas RI did not (p = 0.75) (Table 2). The areas under the ROC curve for the use of corticomedullary strain, EDV, PSV, RI and duration of transplantation to determine >26% renal allograft cortical IF/TA were 0.99, 0.94, 0.88, 0.52 and 0.92, respectively (Table 3, Figs. 7 and 8). The difference in diagnostic performance between two ROC curves was significant (p < 0.05). For testing intra- and inter-observer variability, Pearson\'s correlation coefficient was R2 = 0.95, and the intra-class correlation coefficient was 0.91 (p = 0.000).
The pathogenesis of IF/TA is complex, and the prevention, diagnosis and treatment of IF/TA require more sensitive non-invasive measures and multidisciplinary approaches to melanocortin 1 receptor influence the pathologic changes in the allograft (Li and Yang 2009; Nankivell et al. 2004). Our results indicate that cortical biomechanical properties measured by ultrasound strain are closely correlated with Banff grade cortical fibrosis. However, renal allograft hemodynamic status as assessed by Doppler velocity is correlated only with high-grade and lower-grade cortical fibrosis.
Improving non-invasive tools, such as the imaging techniques discussed here, to detect and measure IF/TA may result in improved care. This non-invasively acquired information has the potential to improve our decision making on biopsies in the management of our patients. In particular, our data support the hypothesis that the progression of cortical IF/TA results in both a decrease in blood flow measured by intra-renal Doppler velocity and an increase in cortical tissue hardness assessed by corticomedullary strain, which may provide more non-invasive measurements that are related to the degree of pathologic damage manifested as cortical IF/TA. Importantly, our study found that corticomedullary strain has high repeatability (R2 = 0.95) and reproducibility (R2 = 0.91) in the assessment of renal allograft cortical IF/TA.
Although our patient population was modest in size, it is interesting that our results are consistent with the concept that renal cortical strain determined by ultrasound may be closely linked to mechanical changes that result in decreased compliance as more fibrotic tissue develops in the cortex. The more compliant the tissue is, the greater is the deformation or “strain” that will develop as a result of palpation or compression. Our data in this study support this hypothesis that fibrotic tissue directly contribute to a decrease in cortical elasticity, because the deformation in the cortex under manual external compression is measurable as the degree of corticomedullary strain and related inversely to the degree of IF/TA in kidney biopsy pathology (odds ratio = −6.097, p = 0.000). With 1.6 as the best cutoff value, the sensitivity and specificity of corticomedullary strain in determining >26% renal allograft cortical IF/TA were 100% and 90% (Table 3), respectively. Because progression of IF/TA is often related to allograft function and the length of time a recipient has had a transplant, it is reasonable to expect decreases in corticomedullary strain and allograft function with increasing duration of transplantation. As we found in our study population, there was a moderate positive correlation between duration of transplantation and severity of renal allograft cortical IF/TA (r2 = 0.67) (Fig. 9). With 29 mo as the optimal cutoff value, the sensitivity and specificity of duration of transplantation in determining >26% cortical IF/TA were 90% and 63%, respectively (Table 3).

Nationalism played an important role in

Nationalism played an important role in maintaining Nicholas’ rule. In 1833, Nicholas I\’s newly appointed Minister of the Department of Education, Sergei Uvarov, sent out his first decree, which would later become known as Nicholas I\’s policy of Official Nationality, the first case of a tsar sponsoring an explicit state ideology since Ivan IV (Hosking, 2001, 267). The decree stated “Our common obligation consists in this that the education of the people be conducted, according to the Supreme intention of our August Monarch, in the joint spirit of Orthodoxy, Autocracy, and Nationality ” (Riasanovsky, 1959, 73). This three-pronged policy, a conscious counterpart to the Liberty, Equality, Fraternity troika of the French Revolution, was a reactionary attempt to legitimize the pre-existing autocracy in the framework of a liberalizing social climate.
Orthodoxy meant devotion and adherence to the Russian Orthodox Church. Christianity provided the basic historical framework for the officials of Official Nationality, but while Nicholas and his followers respected other forms of Christianity, the Orthodox Church was the only form seen as totally authentic (Riasanovsky, 1959, 85). This underscoring of the importance of religion was partially a rejection of the eighteenth century religious skepticism of the European Enlightenment, the dangerous product of which was strongly on Nicholas\’s mind with the revolutionary ethos already infecting Russia. Nicholas believed that in order to suppress these dangerous ideas, people needed to receive a more attentive home education on proper morals and character, which were to be defined by the government. Moreover, the Russian Orthodox Church (ROC) was also essentially subservient to the state, diluting the possibility of Orthodoxy\’s significance as an independent force. Henceforth, the ROC would play a strong hand in teaching obedience to authority, whether it be to tsar, officer, or landlord. Because religion was already a melanocortin 1 receptor phenomenon, the ROC provided a very convenient network for the dissemination of state interests and values.
Official Nationality\’s second pillar, autocracy, was the most straightforward of the three. It was essentially a proclamation against any discussion of constitutional government. There was to be no political role for the Russian people, and no change in the status of most Russians as serfs. In the latter aspect, Nicholas found an ally with the nobility, who naturally wanted to preserve their control over the serfs. Its proponents justified it both with reference to Russian history as well as negative views about human nature in general and the capacities of the average Russian in particular. Mikhail Pogodin, a prominent historian whose father had been a serf, was a strong proponent of state power (gosudarstvennik) and supporter of Nicholas\’ autocratic reign. He contended that “the Russian people is marvelous, but marvelous so far only in potential. In actuality, it is low, horrid, and beastly” (Tolz, 2001, 78). The aforementioned Uvarov believed that Adam\’s fall was the “key to all history” and man\’s essential wickedness required autocratic rule (Anderson, 1987, 174). Nicholas himself embraced a pessimistic view of the capabilities of most Russians (Riasanovsky, 1959, 99). These ideas were all employed to present the benign tsar, a gift from God, as the essential glue that held Russian society together. Lastly, autocracy was not just the clearest of the three points, it was the only one that offered any real solidifying force for the people of the Russian Empire; everybody could identify as a subject of the tsar, regardless of creed or ethnicity.
Nationality (narodnost) was the vaguest of these three terms and potentially problematic in a multinational empire in which many of the leading officials were ethnically German. The addition of this term, however, acknowledged a role for the Russian people (narod) as well as the influence of ideas of nationalism within Russia. If it were not for this final point, the whole policy would have been a direct replication of the mentality behind the Holy Alliance of Nicholas\’ predecessor, Alexander I. The Holy Alliance contextualized the superiority and necessity of monarchical rule within a heavily religious framework against liberal, constitutional ideas, but Nicholas did not leave it at that. There had to be an answer offered to the nationally-oriented dissent that shocked Nicholas\’s early years as tsar. Official Nationality\’s third point, as Geoffrey Hosking explains it, “was an obeisance to the latest developments in European culture, a pale reflection of post-French revolutionary nationalism” (Hosking, Russia, 267). By including this element, Nicholas\’ government could claim recognition of the will of the people without having to provide any institutionalized route for the expression of public opinion. In other words, it was politically hollow compared to the original intention behind Western conceptions of nationalism, which was largely directed against monarchical power. In Russia, nationalism took on a cultural, Romantic cast, manifested in intellectual and artistic projects (e.g. landscape painting) to foster notions of national unity and bridge the massive gap between the landed elite and the peasantry (Ely, 2002, 134).

br We found that higher BMI and higher tidal

We found that higher BMI and higher tidal volume were independently associated with the increased excursions of the bilateral melanocortin 1 receptor by both univariate and multivariate analyses, although the strength of these associations was weak. We cannot explain the exact reason for the correlation between BMI and the excursion of the diaphragm. However, a previous study showed that BMI is associated with peak oxygen consumption (23), and the increased oxygen consumption in an obese participant may affect diaphragmatic movement. Another possible reason is that lower thoracic compliance due to higher BMI may cause increased movement of the diaphragm for compensation. Regarding the correlation between tidal volume and excursion of the diaphragm, given that diaphragmatic muscle serves as the most important respiratory muscle, the result is to be expected. Considering our results, the excursion evaluated by dynamic X-ray phrenicography could potentially predict tidal volume.

Our study has several limitations. First, we included only 172 volunteers, and additional studies on larger participant populations are required to confirm these preliminary findings. Second, we evaluated only the motion of the highest point of the diaphragms for the sake of simplicity, and three-dimensional motion of the diaphragm could not be completely reflected in our results. However, we believe that this simple method would be practical and more easily applicable in a clinical setting.


The time-resolved quantitative analysis of the diaphragms with dynamic X-ray phrenicography is feasible. The average excursions of the diaphragms are 11.0 mm (right) and 14.9 mm (left) during tidal breathing in a standing position in our health screening center cohort. The diaphragmatic motion of the left is significantly larger and faster than that of the right. Higher tidal volume and BMI are associated with increased excursions of the bilateral diaphragm.

AcknowledgmentsThe authors acknowledge the valuable assistance of Hideo Ogata, MD, PhD, Norihisa Motohashi, MD, PhD, Misako Aoki, MD, Yuka Sasaki, MD, PhD, and Hajime Goto, MD, PhD, from the Department of Respiratory Medicine; Yuji Shiraishi, MD, PhD, from the Department of Respiratory Surgery; and Masamitsu Ito, MD, PhD, Atsuko Kurosaki, MD, Yoichi Akiyama, RT, Kenta Amamiya, RT, and Kozo Hanai, RT, PhD, from the Department of Radiology, Fukujuji Hospital, for their important suggestions. The authors also acknowledge the valuable assistance of Alba Cid, MS, for editorial work on the manuscript. Yoshitake Yamada, MD, PhD, is a recipient of a research fellowship from the Uehara Memorial Foundation.

Appendix. Supplementary DataThe following is the supplementary data to this article:
To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowVideo S1.
 A representative video of sequential chest radiographs obtained by chest dynamic radiography for the motion of the diaphragms (“dynamic X-ray phrenicography”). A board-certified radiologist placed a point of interest (red point) on the highest point of each diaphragm on the radiograph at the resting end-expiratory position. These points were automatically traced by the template-matching technique throughout the respiratory phase. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (Fig 2c).Help with MP4 filesOptionsDownload video (1042 K)
Data S1.
 Multivariate analysis of associations between the excursions and participant demographics using age, gender, BMI, tidal volume, VC, FEV1, and smoking history as factors (Model 2).Help with DOCX filesOptionsDownload file (23 K)

The bilateral diaphragm is the most important respiratory muscle. Diaphragmatic dysfunction is an underappreciated cause of respiratory difficulties and may be due to a wide variety of issues, including surgery, trauma, tumor, and infection (1). Several previous studies have evaluated diaphragmatic motion using fluoroscopy 2; 3; 4 ;  5, ultrasound 6 ;  7, magnetic resonance (MR) fluoroscopy (dynamic MR imaging [MRI]) 8; 9; 10; 11 ;  12, and computed tomography (CT) 13; 14; 15 ;  16. However, the data of the previous studies using ultrasound, MR fluoroscopy, or CT were obtained in a supine position 6; 7; 8; 9; 10; 11; 12; 13; 14; 15 ;  16, not in a standing position. Also, while the data of the previous studies using fluoroscopy were obtained in a standing position, the data were assessed under forced breathing 2 ;  3, not under tidal or resting breathing. Thus, diaphragmatic motion in a standing position during tidal breathing remains unclear, even though it is essential for understanding respiratory physiology in our daily life. Furthermore, the evaluation of diaphragmatic motion using fluoroscopy, ultrasound, dynamic MRI, or CT has not been used as a routine examination because of limitations, including high radiation dose, small field of view, low temporal resolution, and/or high cost.

Image Analysis The diaphragmatic motions on sequential

Image Analysis
The diaphragmatic motions on sequential chest radiographs (dynamic image data) during tidal breathing were analyzed using prototype software (Konica Minolta, Inc.) installed in an independent workstation (Operating system: Windows 7 Pro SP1; Microsoft, Redmond WA; CPU: Intel Core i5-5200U, 2.20 GHz; memory 16 GB). The edges of the diaphragms on each dynamic chest radiograph were automatically determined by means of edge detection using a Prewitt Filter 18 ; 19. A board-certified radiologist with 14 years of experience in interpreting chest radiography selected the highest point of each melanocortin 1 receptor as the point of interest on the radiograph of the resting end-expiratory position (Fig 2a). These points were automatically traced by the template-matching technique throughout the respiratory phase (Fig 2b, Supplementary Video S1), and the vertical excursions of the bilateral diaphragm were calculated (Fig 2c): the null point was set at the end of the expiratory phase, that is, the lowest point (0 mm) of the excursion on the graph is the highest point of each diaphragm at the resting end-expiratory position. Then the peak motion speed of each diaphragm was calculated during inspiration and expiration by the differential method (Fig 2c). If several respiratory cycles were involved in the 10 to 15-second examination time, the averages of the measurements were calculated.
Figure 2. Representative sequential chest radiographs and the graphs of excursion and peak motion of the diaphragms obtained by chest dynamic radiography (“dynamic X-ray phrenicography”). (a) Radiograph of the resting end-expiratory position. (b) Radiograph of the resting end-inspiratory position. (c) Graph showing the vertical excursions and the peak motion speeds of the bilateral diaphragm. A board-certified radiologist placed a point of interest (red point) on the highest point of each diaphragm on the radiograph at the resting end-expiratory position (a). These points were automatically traced by the template-matching technique throughout the respiratory phase (double arrows in b) (Supplementary Video S1); red double arrow indicates the vertical excursion of the right diaphragm and blue double arrow indicates that of the left diaphragm. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (c). The lowest point (0 mm) of the excursion on the graph indicated that the highest point of each diaphragm was at the resting end-expiratory position (ie, null point was set at the end-expiratory phase) (c). (Color version of figure is available online.)Figure optionsDownload full-size imageDownload high-quality image (305 K)Download as PowerPoint slide
Pulmonary Function Tests
The pulmonary function tests were performed in all participants on the same day of the imaging study. Parameters of pulmonary function tests were measured according to the American Thoracic Society guidelines 20 ; 21 using a pulmonary function instrument with computer processing (DISCOM-21 FX, Chest MI Co, Tokyo, Japan).

d e Filter F View the MathML sourceGF ss

d4 = 3.21252e?37
Filter F1 View the MathML sourceGF1=(ss+sc1)1+R3R2ssc2+1+sc2/sc3s+s2/sc3 R3/R2 = 210.53
fc1 = 2.40 Hz
fc2 = 16.75 Hz
fc3 = 7.234 kHz
Filter F2 View the MathML sourceGF2=11+s/sc2 fc = 16.389 kHz
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Table 3.
melanocortin 1 receptor Input impedance and gains of the transmitting and receiving circuits.
45 Hz 90 Hz 360 Hz 1440 Hz 5760 Hz
GTX (dB) 0.0 ?0.0001 ?0.0014 ?0.0219 ?0.3746
GTX (°) 0.236 0.473 1.890 7.564 30.372
GRX (dB) 23.1559 23.5006 23.5839 23.0667 16.9741
GRX (°) 25.243 10.397 ?10.082 ?52.823 ?192.418
Rin (GΩ) 0.1795 0.0226 ?0.0249 ?0.0249 ?0.0095
Cin (pF) 0.287 0.288 0.289 0.295 0.335
Table options
As an example, the nodal equation at the TX1 transmitter circuit (conductor 2) can be written:
View the MathML sourceIS(2)=iωVoGTRCT=iω[V(2)-V(1)](CT+CS)+iω∑n=17V(n)KM(2,n)
Turn MathJax on
which implies that: KE(2, 2) = ?KE(2, 1) = ?KE(1, 2) = CT + CS (symmetrical matrix) and a term (CT + CS) in KE(1, 1) (see Table 4). The source term IS(3) relative to TX2 is developed in the same way as for TX1. Since the TX1 and TX2 circuits are identical, but with opposite signs for the voltage source, IS(3) = ?IS(2). All other components of IS are equal to zero because of the absence of any source and because IS(1) = IS(2) + IS(3) = 0.
Table 4.
Electronic matrix [KE].
1 (HUY) 2 (TX1) 3 (TX2) 4 (RX1) 5 (RX2) 6 (RP1) 7 (RP2)
1 (HUY) 2(CT + CS) + 2Cin? + CRP ?(CT + CS) ?(CT + CS) ?Cin? ?Cin? 0 ?CRP
2 (TX1) ?(CT + CS) CT + CS 0 0 0 0 0
3 (TX2) ?(CT + CS) 0 CT + CS 0 0 0 0
4 (RX1) ?Cin? 0 0 Cin? 0 0 0
5 (RX2) ?Cin? 0 0 0 Cin? 0 0
6 (RP1) 0 0 0 0 0 0 0
7 (RP2) ?CRP 0 0 0 0 0 CRP
Table options
The derived matrix coefficients are KE(3, 3) = ?KE(3, 1) = ?KE(1, 3) = CT + CS, and the term to be included in KE(1, 1) is (CT + CS) (see Table 4).
We recall that melanocortin 1 receptor the potential reference in the simulations is zero at infinity while the potential of the Huygens capsule differs from zero. Accordingly, all simulated electrode potentials have to be shifted by the potential of the reference Huygens capsule before any comparison between measurements and simulations.
Receiver circuit. The receiver circuit includes, for each boom, a coupling capacitor housed inside the boom itself, a preamplifier in the HASI-I box, inside the capsule, as well as a differential amplifier and several circuits for accommodating the signals to the ADC input, on the PWA-A board. The parameters, gain and input impedance have been estimated from the nominal component values or derived from calibration measurements.
The outputs of the two HASI-I1 and HASI-I2 MIP preamplifiers are connected to a differential amplifier in PWA-A. This signal is then fed into the ADC through two filters whose gains GF1 and GF2 are estimated from the components listed in Table 2.
The preamplifiers represent the most sensitive parts of the receiver for two reasons. First, they are connected to the electrodes through very small capacitors, and stray capacitances that cannot be evaluated with accuracy. Second, preamplifiers and PWA-A board are located inside the capsule that is heated with radioactive elements, while the coupling capacitors lie outside at ~?180 °C. Such a configuration is impossible to simulate in laboratory. The preamplifiers have been calibrated in two experimental conditions: (1) HASI-I MIP preamplifiers and booms at room temperature, and (2) HASI-I MIP preamplifiers at room temperature and booms with coupling circuits at ~?180 °C (liquid nitrogen). The construction of an accurate analytical model supported with calibration data, is detailed in Appendix B. For Titan’s environment, the GPA gain analytic expression is shown in Table 2. The numerical values of gain and input impedance components, Rin and Cin, are shown in Table 3.