Several isotopomers of cyclooctanone were prepared by selective deuterium substitution. Intrinsic isotope effects on $^{13}C$ NMR chemical shifts of these isotopomers were investigated systematically at low temperature. These istope effects were discussed in relation to the preferred boat-chair conformation of cyclooctanone. Deuterium isotope effects on NMR chemical shifts have been known for a long time. Especially in a conformationally mobile molecule, isotope perturbation could affect NMR signals through a combination of isotope effects on equilibria and intrinsic effects. The distinction between intrinsic and nonintrinsic effects is quite difficult at ambient temperature due to involvement of both equilibrium and intrinsic isotope effects. However if equilibria between possible conformers of cyclooctanone are slowed down enough on the NMR time scale by lowering temperature, it should be possible to measure intrinsic isotope shifts from the separated signals at low temperature. $^{13}C$ NMR has been successfully utilized in the study on molecular conformation in solution when one deals with stable conformers or molecules were rapid interconversion occurs at ambient temperature. The study of dynamic processes in general requires analysis of spectra at several temperature. Anet et al. did $^1H$ NMR study of cyclooctanone at low temperature to freeze out a stable conformation, but were not able initially to deduce which conformation was stable because of the complexity of alkyl region in the $^1H$ NMR spectrum. They also reported the $^1H$ and $^{13}C$ NMR spectra of the $C_9-C_{16}$ cycloalkanones with changing temperature from $-80^{\circ}C$ to $-170^{\circ}C$, but they did not report a variable temperature $^{13}C$ NMR study of cyclooctanone. For the analysis of the intrinsic isotope effect with relation to cylooctanone conformation, $^{13}C$ NMR spectra are obtained in the present work at low temperatures (up to $-150^{\circ}C$) in order to find the chemical shifts at the temperature at which the dynamic process can be "frozen-out" on the NMR time scale and cyclooctanone can be observed as a stable conformation. Both the ring inversion and pseudorotational processes must be "frozen-out" in order to see separate resonances for all eight carbons in cyclooctanone. In contrast to $^1H$ spectra, slowing down just the ring inversion process has no apparent effects on the $^{13}C$ spectra because exchange of environments within the pairs of methylene carbons can still occur by the pseudorotational process. Several isotopomers of cyclooctanone were prepared by selective deuterium substitution (fig. 1) : complete deuterium labeling at C-2 and C-8 positions gave cyclooctanone-2, 2, 8, $8-D_4$ : complete labeling at C-2 and C-7 positions afforded the 2, 2, 7, $7-D_4$ isotopomer : di-deuteration at C-3 gave the 3, $3-D_2$ isotopomer : mono-deuteration provided cyclooctanone-2-D, 4-D and 5-D isotopomers : and partial deuteration on the C-2 and C-8 position, with a chiral and difunctional case catalyst, gave the trans-2, $8-D_2$ isotopomer. These isotopomer were investigated systematically in relation with cyclooctanone conformation and intrinsic isotope effects on $^{13}C$ NMR chemical shifts at low temperature. The determination of the intrinsic effects could help in the analysis of the more complex effects at higher temperature. For quantitative analysis of intrinsic isotope effects, the $^{13}C$ NMR spectrum has been obtained for a mixture of the labeled and unlabeled compounds because the signal separations are very small.
Histone deacetylase inhibitor (HDACI) is a new promising candidate as an antineoplastic agent for the treatment of solid and hematologic malignancies. In order to evaluate cell death and to elucidate the related mechanism(s) in NSCLC cells after HDACI, sodium butyrate (SB), a representative HDACI, was used to treat H460 cells for 48 hrs. SB exposure resulted in a significant reduction of cell viability at concentrations below 7.5 mM, and about 50% of cell death occurred at 20 mM. The types of cell death induced by SB were both apoptosis and necrosis, evaluated by Annexin-V staining combined with propidium iodide. SB treatment significantly evoked G2/M cell cycle arrest and subsequently induced cell death with caspase-dependent manner. While ERK protein content was not altered after SB, phosphorylated forms of ERK were markedly reduced. Taken together, SB is significantly able to induce cell death in NSCLC cell line H460, and it is suggested that the reduction of ERK phosphorylation might be closely involved in the cancer cell death mechanism initiated by HDACI.
Sa, Doo-Hwan;Choi, Hee-Cheol;Kim, Young-Lok;Lee, Seung-Hoon
Journal of the Institute of Electronics Engineers of Korea SD
/
v.43
no.11
s.353
/
pp.58-68
/
2006
This work proposes a 10b 250MS/s $1.8mm^2$ 85mW 0.13um CMOS A/D Converter (ADC) for high-performance integrated systems such as next-generation DTV and WLAN simultaneously requiring low voltage, low power, and small area at high speed. The proposed 3-stage pipeline ADC minimizes chip area and power dissipation at the target resolution and sampling rate. The input SHA maintains 10b resolution with either gate-bootstrapped sampling switches or nominal CMOS sampling switches. The SHA and two MDACs based on a conventional 2-stage amplifier employ optimized trans-conductance ratios of two amplifier stages to achieve the required DC gain, bandwidth, and phase margin. The proposed signal insensitive 3-D fully symmetric capacitor layout reduces the device mismatch of two MDACs. The low-noise on-chip current and voltage references can choose optional off-chip voltage references. The prototype ADC is implemented in a 0.13um 1P8M CMOS process. The measured DNL and INL are within 0.24LSB and 0.35LSB while the ADC shows a maximum SNDR of 54dB and 48dB and a maximum SFDR of 67dB and 61dB at 200MS/s and 250MS/s, respectively. The ADC with an active die area of $1.8mm^2$ consumes 85mW at 250MS/s at a 1.2V supply.
Purpose : Early detection of small brain metastases is important. The purpose of this study was to compare the detectability of brain metastases according to the size between 1.5 T and 3.0 T MRI. Materials and Methods : We reviewed 162 patients with primary lung cancer who were examined for TNM staging. After administration of double dose of Gd-DTPA, MR imaging was performed with SPGR by 3.0 T MRI and then with T1 SE sequence by 1.5 T MRI. In each patient, three readers performed qualitative assessment. Sensitivity, positive predictive value, and diagnostic accuracy were calculated in 3.0 T and 1.5 T MRI according to size. Using the signal intensity (SI) measurements between the metastatic nodules and adjacent tissue, nodule-to-adjacent tissue SI ratio was calculated. Results : Thirty-one of 162 patients had apparent metastatic nodules in the brain at either 1.5 T or 3.0 T MR imaging. 143 nodules were detected in 3.0 T MRI, whereas 137 nodules were detected at 1.5 T MRI. Six nodules, only detected in 3.0 T MRI, were smaller than 3.0 mm in dimension. Sensitivity, positive predictive value, and diagnostic accuracy in 3.0 T MRI were 100 %, 100 %, and 100 % respectively, and in 1.5 T MRI were 95.8%, 88.3%, and 85.1% respectively. SI ratio was significantly higher in the 3.0 T MRI than 1.5 T MRI (p=0.025). Conclusion : True positive rate of 3.0 T MRI with Gd-DTPA was superior to 1.5 T MRI with Gd-DTPA in detection of metastatic nodules smaller than 3.0 mm.
Journal of the Institute of Electronics Engineers of Korea SD
/
v.46
no.3
/
pp.75-85
/
2009
This work proposes a 13b 100MS/s 0.13um CMOS ADC for 3G communication systems such as two-carrier W-CDMA applications simultaneously requiring high resolution, low power, and small size at high speed. The proposed ADC employs a four-step pipeline architecture to optimize power consumption and chip area at the target resolution and sampling rate. Area-efficient high-speed high-resolution gate-bootstrapping circuits are implemented at the sampling switches of the input SHA to maintain signal linearity over the Nyquist rate even at a 1.0V supply operation. The cascode compensation technique on a low-impedance path implemented in the two-stage amplifiers of the SHA and MDAC simultaneously achieves the required operation speed and phase margin with more reduced power consumption than the Miller compensation technique. Low-glitch dynamic latches in sub-ranging flash ADCs reduce kickback-noise referred to the differential input stage of the comparator by isolating the input stage from output nodes to improve system accuracy. The proposed low-noise current and voltage references based on triple negative T.C. circuits are employed on chip with optional off-chip reference voltages. The prototype ADC in a 0.13um 1P8M CMOS technology demonstrates the measured DNL and INL within 0.70LSB and 1.79LSB, respectively. The ADC shows a maximum SNDR of 64.5dB and a maximum SFDR of 78.0dB at 100MS/s, respectively. The ABC with an active die area of $1.22mm^2$ consumes 42.0mW at 100MS/s and a 1.2V supply, corresponding to a FOM of 0.31pJ/conv-step.
Journal of the Institute of Electronics and Information Engineers
/
v.53
no.5
/
pp.87-97
/
2016
This work proposes a time-shared 10b DAC based on a two-step resistor string to minimize the effective area of a DAC channel for driving each AMOLED display column. The proposed DAC shows a lower effective DAC area per unit column driver and a faster conversion speed than the conventional DACs by employing a time-shared DEMUX and a ROM-based two-step decoder of 6b and 4b in the first and second resistor string. In the second-stage 4b floating resistor string, a simple current source rather than a unity-gain buffer decreases the loading effect and chip area of a DAC channel and eliminates offset mismatch between channels caused by buffer amplifiers. The proposed 1-to-24 DEMUX enables a single DAC channel to drive 24 columns sequentially with a single-phase clock and a 5b binary counter. A 0.9pF sampling capacitor and a small-sized source follower in the input stage of each column-driving buffer amplifier decrease the effect due to channel charge injection and improve the output settling accuracy of the buffer amplifier while using the top-plate sampling scheme in the proposed DAC. The proposed DAC in a $0.18{\mu}m$ CMOS shows a signal settling time of 62.5ns during code transitions from '$000_{16}$' to '$3FF_{16}$'. The prototype DAC occupies a unit channel area of $0.058mm^2$ and an effective unit channel area of $0.002mm^2$ while consuming 6.08mW with analog and digital power supplies of 3.3V and 1.8V, respectively.
Tooth movement is the result of bone metabolism in the periodontium, where various cytokines take important roles. Interleukin-6(II-6) and nitrous oxide (NO) were reported to be secreted from osteoblasts in the process of bone resorption. The mechanism of the process has not been clearly understood, but the activation of mitogen-activated protein kinase (MAPK) was known to be an important process in the release of the inflammatory cytotines in macrophages. In this regard, to prove the role of MAPK in the release of IL-6 and NO in MC3T3E-1 osteoblasts, Northern blot analysis, Western blot analysis and immune complex kinase assay were used. As a result, the treatment of MC3T3E-1 osteoblast cultures with combined $interferon-\gamma(IFN-\gamma)$, lipopolysaccharide (LPS) and tumor necrosis $factor-\alpha(TNF-\alpha)$ induces expressions of inducible nitric oxide synthase (iNOS) and IL-6, resulting in sustained releases of large amounts of NO and IL-6. However, $IFN-\gamma,\;LPS,\;and\;TNF-\alpha$ individually induce a non-detectable or small amount of NO and IL-6 in MC3T3E-1 osteoblasts. The role of MAPK activation in the early intracellular signal transduction involved in iNOS and IL-6 transcription in the combined agents-stimulated osteoblasts has been investigated. The p38 MAPK pathway is specifically involved in the combined agents-induced NO and IL-6 release, since NO and IL-6 release in the presence of a specific inhibitor of p38 MAPK, 4-(4-fluorophenyl)-2-(4-metylsulfinylphenyl)-5-(4-metylsulfinylphenyl)-5-(4-pyridyl)imidazole) (SB203580), were significantly diminished. In contrast, PD98059, a specific inhibitor of MEK1, had no effect on NO and IL-6 release. Northern blot analysis showed that the p3a MAPK pathway controlled the iNOS and IL-6 transcription level. These data suggest that p38 MAPK play an important role in the secretion of NO and IL-6 in $LPS/IFN{\gamma}-or\;TNF-\gamma-treated\;MC3T3E-1$ osteoblasts.
Purpose: Low dose of PET/CT is important because of Patient's X-ray exposure. The aim of this study was to evaluate the effectiveness of low-dose PET/ CT image through the CTAC and QAC of patient study and phantom study. Materials and Methods: We used the discovery 710 PET/CT (GE). We used the NEMA IEC body phantom for evaluating the PET data corrected by ultra-low dose CT attenuation correction method and NU2-94 phantom for uniformity. After injection of 70.78 MBq and 22.2 MBq of 18 F-FDG were done to each of phantom, PET/CT scans were obtained. PET data were reconstructed by using of CTAC of which dose was for the diagnosis CT and Q. AC of which was only for attenuation correction. Quantitative analysis was performed by use of horizontal profile and vertical profile. Reference data which were corrected by CTAC were compared to PET data which was corrected by the ultra-low dose. The relative error was assessed. Patients with over weighted and normal weight also underwent a PET/CT scans according to low dose protocol and standard dose protocol. Relative error and signal to noise ratio of SUV were analyzed. Results: In the results of phantom test, phantom PET data were corrected by CTAC and Q.AC and they were compared each other. The relative error of Q.AC profile was been calculated, and it was shown in graph. In patient studies, PET data for overweight patient and normal weight patient were reconstructed by CTAC and Q.AC under routine dose and ultra-low dose. When routine dose was used, the relative error was small. When high dose was used, the result of overweight patient was effectively corrected by Q.AC. Conclusion: In phantom study, CTAC method with 80 kVp and 10 mA was resulted in bead hardening artifact. PET data corrected by ultra- low dose CTAC was not quantified, but those by the same dose were quantified properly. In patients' cases, PET data of over weighted patient could be quantified by Q.AC method. Its relative difference was not significant. Q.AC method was proper attenuation correction method when ultra-low dose was used. As a result, it is expected that Q.AC is a good method in order to reduce patient's exposure dose.
Han, Yong Su;Kim, Ho Chul;Lee, Dong Young;Lee, Su Cheol;Ha, Seung Han;Kim, Min Gi
Journal of the Institute of Electronics and Information Engineers
/
v.51
no.12
/
pp.180-188
/
2014
It is very important accurate diagnosis and quick treatment in cerebrovascular disease, i.e. stenosis or occlusion that could be caused by risk factors such as poor dietary habits, insufficient exercise, and obesity. Time-of-flight magnetic resonance angiography (TOF-MRA), it is well known as diagnostic method without using contrast agent for cerebrovascular disease, is the most representative and reliable technique. Nevertheless, it still has measurement errors (also known as overestimation) for length of stenosis and area of occlusion in celebral infarction that is built by accumulation and rupture of plaques generated by hemodynamic turbulence. The purpose of this study is to show clinical trial feasibility for 3D-SPACE T2, which is improved by using signal attenuation effects of fluid velocity, in diagnosis of cerebrovascular disease. To model angiostenosis, strictures of different proportions (40%, 50%, 60%, and 70%) and virtual blood stream (normal saline) of different velocities (0.19 ml/sec, 1.5 ml/sec, 2.1 ml/sec, and 2.6 ml/sec) by using dialysis were made. Cross-examinations were performed for 3D-SPACE T2 and TOF-MRA (16 times each). The accuracy of measurement for length of stenosis was compared in all experimental conditions. 3D-SPACE 2T has superiority in terms of accuracy for measurements of the length of stenosis, compared with TOF-MRA. Also, it is robust in fast blood stream and large stenosis than TOF-MRA. 3D-SPACE 2T will be promising technique to increase diagnosis accuracy in narrow complex lesions as like two cerebral small vessels with stenosis, created by hemodynamic turbulence.
The Journal of the Korean bone and joint tumor society
/
v.20
no.2
/
pp.74-79
/
2014
Purpose: Fibrous dysplasia is related to the mutation of gene encoding the alpha-subunit of a signal-transducing G-protein and has variable clinical course. Operation can be performed to prevent functional disorder or structural deformity. After curettage, autologous bone graft were used to fill the defects after curettage. The aim of this study is to compare the result of autogenous cancellous bone grafting and allogenic bone grafting for fibrous dysplasia. Materials and Methods: Among the patients who visit our hospital during the period of April, 1997 to October, 2013, we selected 34 patients who diagnosed fibrous dysplasia and visited our clinic over 1 year. There were 13 males and 21 females. Average age was 26.4 (range 2 to 57) years old. Autogenous bone graft (group I) in 5 cases, Non-autogenous bone graft (group II) in 30 cases. Iliac bone is used in all cases of autogenous bone graft. There were no significant difference in age, follow-up period, preoperational laboratory finding between two groups. Radiographic image was done to evaluate the recurrence of fibrous dysplasia or secondary degeneration. Results: There were four cases in recurrence (group I: 1 case, group II: 3 cases, p=0.554). In all recurrent cases, reoperations were done using curettage and autogenous iliac bone graft. There was no re-recurrence after reoperation. One case of secondary aneurysmal bone cyst was confirmed (group II) and 1 cases of pathologic fractures had developed (group I: 0 case, group II: 1 cases, p=0.559). No malignant change occurred. Conclusion: There were no significant difference between autogenous bone graft group and non-autogenous bone graft group. Our result suggested that autogenous bone graft seems to be good method to treat fibrous dysplasia, in the case of small volume of tumor lesion or non-weight bearing portion.
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