An Optimal Design Method for CMOS Even-Stage Ring Oscillators Containing Plural Latches

2009 International Conference on Solid State Devices and Materials (SSDM 2009), October 7-9, 2009, Sendai, Miyagi, Japa

ヒト大腸癌組織内チミジル酸合成酵素活性および葉酸プールの測定とユーエフティ投与によるその変動

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1063号, 学位授与年月日：平成4年12月31日,学位授与年：199

An Optimal Design Method for CMOS Even-Stage Ring Oscillators Containing Latches

This paper describes a design method for complementary metal oxide semiconductor (CMOS) ring oscillators composed of even-stage inverters. First, we propose a quantitative method to evaluate oscillation stability for an even-stage ring oscillator with a CMOS latch. The method uses static noise margin analysis to evaluate the static random access memory (SRAM) cell\u27s data storage stability, by observing the similarity between the oscillator and SRAM cell circuitry. Next, the method is extended to oscillators with multiple latches. Finally, by analyzing oscillation stability using this method, we find that the range of stable oscillation conditions can be drastically widened by adding multiple single-channel latch circuits, and also by an appropriate design of their polarities and insertion positions. We also clarify through Monte Carlo simulations, that the optimized oscillator circuit is robust under process, voltage and temperature fluctuations and device characteristic variations

末梢血中遊離DNAのエピジエネティクスを標的とした癌分子診断

金沢大学医薬保健研究域医学系坦癌患者において末梢血に遊離して存在する癌由来DNAのエピジェネティクな変化、すなわちhypermethylation(HM)を検出し、癌の早期診断に利用可能かを検討した。1.PCRにて177塩基対のβアクチン遺伝子断片を作成し、これを牛血清に混入させ各種抽出法にてDNAを抽出した。また、豚末梢血管より上記のDNA断片を注入し各種採血管にて末梢血を採取した。抽出効率、再現性などより、血清採取、A祉キットによるDNA抽出を解析条件として選択した。2、p16,APC遺伝子をターゲットとして、進行大腸癌患者血清20検体を解析した。1例のみで、APC遺伝子のHMを末梢血から検出可能であった。癌原発巣を解析するとP16では3例(15%)、APCでは5例(25%)にHMを認めた。原発巣におけるHMの低頻度が末梢血での低検出頻度の1因と考えられた。3、より高頻度にHMが認められる標的遺伝子検索を進める目的で、大腸癌54例を対象としてp16、APCに加え、hMLH1、ESR1、CALCA、HIC1、MGMT、TIMP3、MYOD1を解析した。p16、APC、hMLH1、TIMP3のHMは癌特異的であったがその頻度は比較的低頻度であった。ESR1、CALCA、HIC1、MGMTでは高頻度のHMを認めたが、癌特異的ではなかった。一方、MYOD1のみが癌組織におけるHMが77.8%と高頻度かつ、正常組織におけるHMが5.6%と比較的癌特異的であった。4、MYOD1をターゲットとし、上記の解析で対象とした大腸癌54例から採取した末梢血を解析した。原発巣においてHMが認められた42例中26例(62%)で末梢血においてもMYOD1のHMが検出可能であった。54例のすべての解析例を含めると末梢血により癌の存在診断が可能と考えられる頻度は48%(54例中26例)であった。研究課題/領域番号:13218051, 研究期間(年度):2001出典：「末梢血中遊離DNAのエピジエネティクスを標的とした癌分子診断」研究成果報告書　課題番号13218051（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-13218051/)を加工して作

BRAF mutations are associated with distinctive clinical, pathological and molecular features of colorectal cancer independently of microsatellite instability status

BACKGROUND: BRAF is a member of RAF family of serine/threonine kinases and mediates cellular responses to growth signals through the RAS-RAF-MAP kinase pathway. Activating mutations in BRAF have recently been found in about 10% of colorectal cancers, with the vast majority being a V600E hotspot mutation. The aim of the present study was to evaluate the clinical, pathological and molecular phenotype of colorectal tumors with BRAF mutations. RESULTS: Mutations in BRAF were identified in 8% (23/275) of colorectal cancers. They were 5–10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (P < 0.002 for each). Tumors with BRAF mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation (P < 0.0001) compared to tumors without this mutation. The characteristic morphological features of tumors with BRAF mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes. Mutations in BRAF were mutually exclusive with mutations in KRAS but showed no clear association with the presence of TP53 mutation. CONCLUSION: BRAF mutation identifies a colorectal cancer subgroup with distinctive phenotypic properties independent of microsatellite instability status and thus could be a valuable marker for studies into the clinical properties of these tumors

A DESIGN METHOD OF BURSTING USING TWO-PARAMETER BIFURCATION DIAGRAMS IN FITZHUGH–NAGUMO MODEL

Spiking and bursting observed in nerve membranes seem to be important when we investigate information representation model in the brain. Many topologically different bursting responses are observed in the mathematical models and their related bifurcation mechanisms have been clarified. In this paper, we propose a design method to generate bursting responses in FitzHugh-Nagumo model with a simple periodic external force based on bifurcation analysis. Some effective parameter perturbations for the amplitude of the external input are given from the 2-parameter bifurcation diagram

Itinerant memory dynamics and global bifurcations in chaotic neural networks

We have considered itinerant memory dynamics in a chaotic neural network composed of four chaotic neurons with synaptic connections determined by two orthogonal stored patterns as a simple example of a chaotic itinerant phenomenon in dynamical associative memory. We have analyzed a mechanism of generating the itinerant memory dynamics with respect to intersection of a pair of ␣ branches of periodic points and collapse of a periodic in-phase attracting set. The intersection of invariant sets is numerically verified by a novel method proposed in this paper. 3,11,12 Among such studies we focus on the associative memory dynamics in this paper. Adachi and Aihara analyzed the dynamics of associative memory networks composed of chaotic neurons in detail and examined characteristics of the retrieval process

BIFURCATIONS IN TWO-DIMENSIONAL HINDMARSH–ROSE TYPE MODEL

We analyze a two-dimensional Hindmarsh-Rose type model exhibiting properties of both Class 1 and Class 2 neurons. Although the system is two-dimensional and contains only four parameters, the obtained bifurcation diagrams show that the bifurcation structure satisfies conditions for emergence of both features with constant stimuli