Optoelectronic parallel-matching architecture : architecture description, performance estimation, and prototype demonstration

This paper was published in Optics Express and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://dx.doi.org/10.1364/AO.40.000283 Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law

Identification of hypoxia-inducible factor 1 ancillary sequence and its function in vascular endothelial growth factor gene induction by hypoxia and nitric oxide.

Transcription of hypoxia-inducible genes is regulated by hypoxia response elements (HREs) located in either the promoter or enhancer regions. Analysis of these elements reveals the presence of one or more binding sites for hypoxia-inducible factor 1 (HIF-1). Hypoxia-inducible genes include vascular endothelial growth factor (VEGF), erythropoietin, and glycolytic enzyme genes. Site-directed mutational analysis of the VEGF gene promoter revealed that an HIF-1 binding site (HBS) and its downstream HIF-1 ancillary sequence (HAS) within the HRE are required as cis-elements for the transcriptional activation of VEGF by either hypoxia or nitric oxide (NO). The core sequences of the HBS and the HAS were determined as TACGTG and CAGGT, respectively. These elements form an imperfect inverted repeat, and the spacing between these motifs is crucial for activity of the promoter. Gel shift assays demonstrate that as yet unknown protein complexes constitutively bind to the HAS regardless of the presence of these stimuli in several cell lines, in contrast with hypoxia- or NO-induced activation of HIF-1 binding to the HBS. A common structure of the HRE, which consists of the HBS and the HAS, is seen among several hypoxia-inducible genes, suggesting the presence of a novel mechanism mediated by the HAS for the regulation of these genes

Structural studies of toxins and toxin-like proteins

Toxins are an ancient mechanism of interaction between cohabiting organisms: basal concentrations serve as an informal cue, enough as a warning signal; too much and the dialog is over. As such, the evolutionary race to arms led to the development of a vast trove of molecular unique biochemical mechanisms, from small molecules to protein toxins. The study of these mechanisms is not only essential for the treatment of toxin-related pathologies, but also as the potential source for novel therapeutic drugs. In this thesis, a series of studies of different toxins and toxin-like proteins are compiled. To further understand the biological function and relevance of each toxin, their detailed study and characterization were pursued. Here are described the advances made using a combination of different complementary biophysical and structural methods, chosen in each case to specifically target each molecule characteristics. In the first chapter, the general biological theme of this thesis is introduced: toxins, particularly protein toxins, their description, and classification, as well as the role of structural biology in the study of proteins in general. To set the theoretical background of the following chapters, are also described the general principles of two of the most prominent methods for the study of proteins in structural biology: nuclear magnetic resonance (NMR) spectroscopy, and X-ray diffraction. In the second chapter, the interaction between human FKBP12 chaperone protein and two similar bacterial small molecule toxins is detailed: rapamycin initially used as an anti-fungal before the discovery of its potent immunosuppressive properties as a mTOR inhibitor; and mycolactone, a bacterial toxin responsible for the disease Buruli ulcers in humans. In the third chapter, the cell-free protein expression system is introduced as a technique best suited for the expression of cytotoxic proteins and otherwise difficult targets, as explored further in the following chapters. In the fourth chapter, advancements towards the structural and conformational characterization of the membrane-inserted state of two similar pore-forming toxins are detailed: the bacterial Colicin Ia protein; and the human Bax protein, an apoptosis effector; using X-ray crystallography, solution NMR and solid-state NMR. Finally, in the fifth chapter, two FIC-domain bacterial toxins are investigated: the bacterial VbhTA toxin-antitoxin protein complex, and the structural determination with its cognate target, DNA GyraseB enzyme; and the auto-activation of the bacterial NmFIC protein; in both cases using a combination of X-ray crystallography and NMR spectroscopy, as well as other biophysical techniques

Application of neutron capture autoradiography to Boron Delivery seeking techniques for selective accumulation of boron compounds to tumor with intra-arterial administration of boron entrapped water-in-oil-in-water emulsion

It isnecessary to accumulate the 10B atoms selectively to the tumor cells for effective Boron Neutron Capture Therapy(BNCT). In order to achieve anaccurate measurement of 10B accumulations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of sliced samples of tumor tissues using CR-39 plastic track detectors. The CR-39 track detectors attached with the biological samples were exposed to thermal neutrons in the thermal column of the JRR3 of Japan Atomic Energy Agency (JAEA). We obtained quantitative NCAR images of the samples for VX-2 tumor in rabbit liver after injection of 10BSH entrapped water-in-oil-in-water (WOW) emulsion by intra-arterial injection via proper hepatic artery. The 10B accumulations and distributions in VX-2 tumor and normal liver of rabbit were investigated by means of alpha-track density measurements. In this study, we showed the selective accumulation of 10B atoms in the VX-2 tumor by intra-arterial injection of 10B entrapped WOW emulsion until 3 days after injection by using digitized NCARimages (i.e.alpha-track mapping)

Age-Related Decrease of the Retinal Vasculature Area Identified with a Novel Computer-Aided Analysis System

信州大学博士（医学）・学位論文・平成25年1月16日授与（乙第1151号）・山本 裕香Fundus photographs enable non-invasive analysis of the status of the microcirculation by directly observing the retinal vasculature. Retinal microvascular abnormalities are important clinical markers of hypertension and arteriosclerosis, but retinal microvascular changes can be observed in older individuals without hypertension. In this study, our goal is to elucidate the effects of aging on fundus vessels in the retinal photograph. We analyzed retinal vessels of 161 healthy volunteers (49.5 +/- 18.7 years, range 18-87) using in-house computer-aided measurement system to measure areas and diameters of all retinal vessels across the entire area of a retinal photograph. The vessels were segmented according to color, and then their area, size, length and thickness were measured by image processing. We also analyzed the correlation between total blood vessel area, age and mean arterial blood pressure (MABP). The decrease in total blood vessel area was dependent on both age and MABP. Moreover, decrease in blood vessel area was also correlated with age for the normotensive group. Furthermore, the slope of the regression line for retinal vessel area with MABP was significantly higher in participants aged <= 60 years than in those aged over 60 years. Changes in retinal vessel area with aging were observed in both arterioles and venules. In conclusion, we found the significant decrease in retinal vessel area that is correlated well with calendar age. Therefore, we need to carefully apply traditional classifications of fundus examination for hypertensive retinopathy in older individuals.ArticleTOHOKU UNIV MEDICAL PRESS. 228(3):229-237 (2012)journal articl

Experimental investigation and hygrothermal modelling of freeze-thaw process of saturated fired clay materials including supercooling phenomenon

To investigate the supercooling phenomenon in fired clay materials, low-temperature differential scanning calorimetry (DSC) and a one-dimensional freeze-thaw (FT) experiment were performed on saturated specimens. The rate of increase in ice saturation during freezing was calculated from the DSC result. Rapid ice growth over a relatively narrow temperature range (within about 0.2 K) was observed at a cooling rate of 0.25 K/min. In the FT experiment, the temperature distribution of a specimen was measured with inserted thermocouples. According to the results of the FT experiment, a rapid temperature increase was observed at sub-zero temperatures accompanied by freezing of the supercooled water. When the supercooled water began to freeze, the released latent heat was found to strongly prevent the specimen temperature from dropping even during the cooling period. Finally, a hygrothermal model of freezing and thawing including a non-equilibrium supercooling process was developed. The freezing rate of the supercooled water was modelled based on the DSC result. The validity of the model was verified by comparing the results of the FT experiment and calculations. The model was found to be able to replicate the rapid temperature rise during the cooling period of the FT experiment