ASAver.1: An FPGA-based education board for computer architecture/system design

Abstract| This paper proposes a new approach that makes it possible for every undergraduate student to perform experiments of developing a pipelined RISC processor within limited time available for the course. The approach consists of 4 steps; at the rst step, modeling of pipelined RISC processor is simplied by avoiding structural hazard and by ignoring other hazards, and in the succeeding steps, students learn diculties of pipelining by themselves. An educational FPGA board ASAver.1 and results of feasibility study are also shown

Transfer RNA Modification Enzymes from Thermophiles and Their Modified Nucleosides in tRNA

To date, numerous modified nucleosides in tRNA as well as tRNA modification enzymes have been identified not only in thermophiles but also in mesophiles. Because most modified nucleosides in tRNA from thermophiles are common to those in tRNA from mesophiles, they are considered to work essentially in steps of protein synthesis at high temperatures. At high temperatures, the structure of unmodified tRNA will be disrupted. Therefore, thermophiles must possess strategies to stabilize tRNA structures. To this end, several thermophile-specific modified nucleosides in tRNA have been identified. Other factors such as RNA-binding proteins and polyamines contribute to the stability of tRNA at high temperatures. Thermus thermophilus, which is an extreme-thermophilic eubacterium, can adapt its protein synthesis system in response to temperature changes via the network of modified nucleosides in tRNA and tRNA modification enzymes. Notably, tRNA modification enzymes from thermophiles are very stable. Therefore, they have been utilized for biochemical and structural studies. In the future, thermostable tRNA modification enzymes may be useful as biotechnology tools and may be utilized for medical science

Joint Degradation in a Monkey Model of Collagen-Induced Arthritis: Role of Cathepsin K Based on Biochemical Markers and Histological Evaluation

The role of cathepsin K in joint degradation in a model of collagen-induced arthritis (CIA) in cynomolgus monkey was examined using biochemical markers and histology. Joint swelling, urinary C-telopeptide of type II collagen (CTX-II), deoxypyridinoline (DPD), and N- and C-telopeptides of type I collagen (NTX and CTX-I, resp.) were analyzed. Immunohistochemistry of type II collagen, cathepsin K, and CTX-II were performed using joints. Joint swelling reached peak on day 42 and continued at this level. The CTX-II level peaked on day 28 and declined thereafter, while CTX-I, NTX, and DPD reached plateau on day 43. Joint swelling was positively correlated with CTX-II increases on days 20 and 42/43, with increases in CTX-I and NTX/Cr on days 42/43 and 84, and with DPD increases throughout the study period. Intense cathepsin K staining was observed in osteoclasts and in articular cartilage and synovial tissue in arthritic joints. CTX-II was present in the superficial layer of articular cartilage in CIA monkeys. Evidence from biochemical markers suggests that matrix degradation in the CIA model starts with degradation of cartilage, rather than bone resorption. Cathepsin K expressed in osteoclasts, articular cartilage, and synovial tissue may contribute to degradation of cartilage

Time taken to the maximum increase in the oxygenated hemoglobin level in calf muscle as a predictor of mild and moderate post-thrombotic syndrome

AbstractBackgroundNear-infrared spectroscopy (NIRS) allows continuous noninvasive monitoring of changes in the tissue levels of oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) and can identify the severity of chronic venous diseases. Here we investigated the predictors of post-thrombotic syndrome (PTS) using NIRS in patients with a first episode of deep venous thrombosis (DVT).MethodsThe study enrolled 129 patients with DVT. Risk factors in each patient were assessed at presentation. Venous abnormalities confirmed by ultrasound and parameters derived from NIRS were evaluated at 6 months after DVT. On standing, increases in O2Hb and HHb (ΔO2Hbst and ΔHHbst) and the times taken for each concentration to become maximal (TO2Hbst, and THHbst) were measured. During 10 tiptoe movements, O2Hb showed a continuous decrease (ΔO2Hbex), whereas venous expulsion (ΔHHbEex) and subsequent retention (ΔHHbRex) were observed. The oxygenation index (HbD; HbD = O2Hb − HHb) was also calculated at the end of standing and at the end of 10 tiptoe movements (ΔHbDst and ΔHbDex). Final clinical manifestations were evaluated at 6 years, and PTS was considered to be present if the Villalta score was ≥5.ResultsThirteen patients were excluded and 116 patients were finally included. Of these, 19 (16%) developed PTS. Among various NIRS-derived parameters, TO2Hbst had the highest area under the curve (0.88; 95% confidence interval [CI], 0.80-0.93; P < .01) with the best cutoff value (TO2Hbst ≤48 seconds). On univariate analysis, variables associated with greater risk for development of PTS were stroke (odds ratio [OR], 5.59; 95% CI, 0.74-42.41; P = .06), idiopathic DVT (OR, 4.13; 95% CI, 1.36-12.55; P < .01) and iliofemoral DVT (OR, 4.31; 95% CI, 1.48-12.60; P < .01) at initial presentation, venous occlusion combined with reflux (OR, 4.24; 95% CI, 1.50-12.00; P < .01), and NIRS-derived TO2Hbst ≤48 seconds (OR, 43.03; 95% CI, 9.04-204.81; P < .01) at 6 months. Multivariate logistic regression analysis finally revealed venous occlusion combined with reflux (OR, 4.80; 95% CI, 1.03-22.36; P < .05) and NIRS-derived TO2Hbst ≤48 seconds (OR, 53.73; 95% CI, 8.43-342.41; P < .01) to be independently associated with PTS progression.ConclusionsNIRS-derived TO2Hbst ≤48 seconds is a promising time-course predictor of PTS progression

Application of susceptibility weighted imaging (SWI) for evaluation of draining veins of arteriovenous malformation: utility of magnitude images.

INTRODUCTION: The current study evaluated the signal characteristics of susceptibility weighted imaging (SWI) of arteriovenous malformation (AVM), especially for draining veins. For this purpose, we identified the draining veins of the AVM on angiography and evaluated the signal on magnitude image for SWI (SWI-mag) and minimum intensity projection image (SWI-minIP). METHODS: Subjects were 14 cases with angiographically proven AVM. SWI-mag, SWI-minIP, and time-of-flight (TOF) magnetic resonance angiography were acquired. For the draining veins of the AVM identified on angiography, we analyzed signal intensity on the images listed above, and classified it into hyperintensity (hyper), mixed intensity (mixed), hypointensity (hypo), and no visualization. RESULTS: On the analysis of 27 angiographically proven draining veins, 19 draining veins were classified as hyper, 3 as mixed, 0 as hypo, and 6 as no visualization on SWI-mag. On TOF images, 21 draining veins were classified as hyper, 2 as mixed, 0 as hypo, and 4 as no visualization, while 6 draining veins did not show hyperintensity on TOF, and SWI-mag visualized 3 of these 6 veins as hyper. CONCLUSION: SWI-mag depicted most draining veins of AVM as hyperintensity. We speculate that this is mainly due to the higher concentration of oxygenated hemoglobin (oxy-Hb) and inflow effect of the draining vein. SWI-mag seems to be useful in the analysis and follow-up for AVM as the signal on the image may reflect physiological status.博士（医学）・乙第1316号・平成25年7月22

転移性脳腫瘍の倍量造影剤投与における、分割投与と単回投与の病変描出能の比較

PURPOSE: As stereotactic radiotherapy (SRT) becomes widespread, precise information including number, location, and margin of lesions is required when magnetic resonance (MR) imaging of brain metastasis is performed. We compare methods using 2 separate injections and a single injection for the administration of a double dose of contrast medium for contrastenhanced MR imaging. MATERIALS AND METHODS: We divided 40 patients with brain metastasis into 2 groups of 20 patients. Group A received 2 separate injections (0.2 + 0.2 mL/kg) of contrast medium (gadoteridol); Group B received a single injection of the same total dose (0.4 mL/kg). Group A underwent spin echo (SE) T1-weighted imaging (T1WI) and magnetization prepared rapid acquisition with gradient echo sequence (MPRAGE) after each injection, and Group B underwent the same MR studies at the same timing as Group A. We evaluated the number, signal-to-noise ratio (SNR), diameter, margin delineation, and volume of lesions and compared them between early and delayed studies by the 2 methods. RESULTS: The number of detected lesions was largest in delayed studies of MPRAGE in both groups. The SNR of the lesions was statistically lower in early studies of Group A than other studies. Delayed studies of Group B showed statistically better margin delineation than other studies on both SE-T1WI and MPRAGE studies. Diameter and enhanced volume were statistically significantly larger on delayed phase than early phase in both groups. CONCLUSION: Use of a single injection of double-dose contrast medium and longer delay time may improve margin delineation of lesions for the study of brain metastasis. Enhanced volume was larger on delayed phase, and it may influence selection of therapeutic strategy.博士（医学）・乙第1356号・平成27年3月16日Copyright © 2014 by Japanese Society for Magnetic Resonance in Medicine著作権は日本磁気共鳴医学会に帰属日本磁気共鳴医学会及び著者（共著者も含む）の許諾を得て登

Role of Elf3 in diabetic nephropathy

Diabetic nephropathy (DN) is among the most serious complications of diabetes mellitus, and often leads to end-stage renal disease ultimately requiring dialysis or renal transplantation. The loss of podocytes has been reported to have a role in the onset and progression of DN. Here, we addressed the activation mechanism of Smad3 signaling in podocytes. Expression of RII and activation of Smad3 were induced by AGE exposure (P<0.05). Reduction of the activation of RII-Smad3 signaling ameliorated podocyte injuries in Smad3-knockout diabetic mice. The bone morphogenetic protein 4 (BMP4) significantly regulated activation of RII-Smad3 signalings (P<0.05). Moreover, the epithelium-specific transcription factor, Elf3was induced by AGE stimulation and, subsequently, upregulated RII expression in cultured podocytes. Induction of Elf3 and activation of RII-Smad3 signaling, leading to a decrease in WT1 expression, were observed in podocytes in diabetic human kidneys. Moreover, AGE treatment induced the secretion of Elf3-containing exosomes from cultured podocytes, which was dependent on the activation of the TGF-β-Smad3 signaling pathway. In addition, exosomal Elf3 protein in urine could be measured only in urinary exosomes from patients with DN. The appearance of urinary exosomal Elf3 protein in patients with DN suggested the existence of irreversible injuries in podocytes. The rate of decline in the estimated Glomerular Filtration Rate (eGFR) after measurement of urinary exosomal Elf3 protein levels in patients with DN (R2 = 0.7259) might be useful as an early non-invasive marker for podocyte injuries in DN