Suppression of ANP gene transcription by liganded vitamin D receptor: involvement of specific receptor domains

We showed previously that liganded vitamin D receptor (VDR) effects a suppression of human atrial natriuretic peptide (hANP) gene-promoter activity in cultured neonatal rat atrial myocytes. In the present study, we have attempted to identify the structural domains of the VDR that are involved in mediating this suppression. We examined the effects of a series of VDR mutants on a cotransfected hANP promoter-driven chloramphenicol acetyltransferase (CAT) reporter. Neither the native VDR nor any of the mutants tested displayed inhibitory activity in the absence of the 1,25-dihydroxyvitamin D3 (VD3) ligand. Delta134, a deletant harboring solely the DNA binding region of the VDR, and L254G, a mutant shown to be defective in retinoid X receptor (RXR) heterodimer formation in other systems, were as effective as the native VDR in reducing promoter activity. HBD, a deletant containing only the hormone-binding domain of the VDR, and K246G, a point mutant that is defective in the activation function of the receptor, did not attenuate reporter activity. A similar activity profile was displayed when a positively regulated promoter containing a direct-repeat vitamin D responsive element (DR3-CAT) was examined in these cells. Liganded VDR, the delta134 mutant, and liganded L254G effected increases in DR3-CAT activity of 2.5-, 2-, and 4-fold, respectively. Two nonhypercalcemic analogues of VD3 (RO 23-7553 and RO 25-6760) displayed the same inhibitory activity as VD3. These studies suggest that the inhibition of hANP promoter activity requires both the DNA binding and activation functions of the receptor but does not appear to require formation of a classic RXR alpha-VDR heterodimer.     

Injury probability and risk in frontal crashes: effects of sorting techniques on priorities for offset testing

A hydrazinonicotinamide-functionalized cyclic platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist [HYNICtide, cyclo(D-Val-NMeArg-Gly-Asp-Mamb(5-(6-(6-hydrazinonicotina mido)hexanamide)))] was labeled with 99mTc using tricine and a series of imine-N-containing heterocycles as coligands. The imine-N-containing heterocycles include N-omega-Acetylhistamine (HIS-AC), N-(2-hydroxyethyl)isonicotinamide (ISONIC-HE), isonicotinic acid (ISONIC), isonicotinoyl-L-aspartic acid dimethyl ester (ISONIC-L-Asp-OMe2), 4-methyl-5-thiazoleethanol (MTE), nicotinic acid (NIC), 3-nitro-1,2,4-triazole (NTZ), 4-pyridylacetic acid (PA), 4-pyridineethanesulfonic acid (PES), and 3-pyridinesulfonic acid (PSA). The synthesis of these new ternary ligand [99mTc]HYNICtide complexes can be performed in one or two steps in high yield and high specific activity (>/=10 000 Ci/mmol HYNICtide). For example, the reaction of HYNICtide, [99mTc]pertechnetate, nicotinic acid, stannous chloride, and tricine at pH approximately 5 and 100 degreesC for 20 min results in the complex [99mTc(HYNICtide)(tricine)(NIC)] in >/=90% yield as determined by radio-HPLC. It was found that ternary ligand technetium complexes, [99mTc(HYNICtide)(tricine)(L)] (L = ISONIC, ISONIC-L-Asp-OMe2, ISONIC-HE, MTE, PA, PES, and PSA) are formed as equal mixtures of two isomeric forms. Complex [99mTc(HYNICtide)(tricine)(L)] (L = HIS-AC and NTZ) showed more than two well-resolved radiometric peaks at the retention times of interest, suggesting that they may have more than two forms in solution due to different bonding modalities of HIS-AC and NTZ. By a chirality experiment, it was found that the presence of two radiometric peaks is a result of the resolution of the two diastereomers which are formed by the combination of the chiral HYNICtide and the chiral technetium chelate. The formation of two diastereomers was also observed when a chiral imine-N-containing coligand was used for the radiolabeling of HYNIC-BA. The new ternary ligand [99mTc]HYNICtide complexes were found to be stable for up to 6 h in the reaction mixture. The high solution stability is attributed to their kinetic inertness. The composition of these complexes was determined to be 1:1:1:1 for Tc:HYNICtide:L:tricine (L = imine-N-containing heterocycles) through a series of mixed ligand experiments on the tracer (99mTc) level. The lipophilicity of the ternary ligand [99mTc]HYNICtide complexes can be systematically varied by the choice of polyaminocarboxylate and imine-N-containing coligands. Using the combination of tricine and an imine-N-containing coligand, HYNIC-derivatized peptides or other small molecules can be labeled with 99mTc in high specific activity and high stability for potential use as radiopharmaceuticals.     

Low light conditions modelling for building integrated photovoltaic (BIPV) systems

The low irradiance efficiency of photovoltaic modules is important to the optimization of BIPV systems. When photovoltaic modules are integrated into a building, architectural design considerations compete with maximizing photovoltaic energy production. As a result, BIPV arrays are often not facing south and are frequently mounted vertically. Under these conditions, a greater portion of the total sunlight striking the array is diffuse or at high angles of incidence. In northern latitudes a significant amount of the total yearly energy is produced at low light levels.A grid-connected array of BIPV modules integrated into the BCIT Technology Centre building in Burnaby, B.C. was used for assessing the accuracy of an energy performance model developed for BIPV systems. The BIPV system uses AC modules and a computerized data acquisition system for monitoring the performance of modules and inverters. The performance model was developed from analysis of the open circuit voltage, maximum power point voltage and maximum power point current of the individual modules comprising the BIPV array.The algorithm for calculating power output of the photovoltaic array is derived from the ideal diode equation using the single diode model of a photovoltaic cell. An empirically derived parameter modifies the equation. Once the parameters for different module technologies are established, it is possible to compare their annual performance in a BIPV system.     

Orthopantomographic X-ray findings, not due to jaws or teeth, and their interpretation

An attempt was made to make an early diagnosis of intrauterine growth retardation due to chronic placental insufficiency using ultrasound cephalometry and biochemical tests of placental function. We examined 83 hospitalised patients in whom there was a risk or suspicion of chronic placental insufficiency. For each patient an average of 4 determinations were made of head diameter, 10 of estriol and 3 of pregnandiol urinary excretion, 6 serum HPL and 7 of heat stable alkaline phosphatase (HSAP). Fetal growth retardation was assumed if the last 2 determined head diameters were below the normal curve with the same tendency and with term being well predicted. Biochemical parameters were considered to indicate pathological changes if they were 95% below normal values, with 2 below this range or 3 continuously falling below the normal level. Infants were assessed after birth both neurologically and somatically according to DUBOWITZ. Small for date infants were those whose birth weight was below the 10th percentile (LUBCHENKO). This was found to be the case in 15 out of 83 newborns five of whom were younger than 37 weeks. These 15 could be diagnosed before birth with various degrees of certainty. For estriol and HPL this was 67% or 53% and these two parameters were found to be the most valuable. Cephalometry was found to be less valuable with 20%, pregnandiol levels with 9% and placental HSAP with 33%. Hence it is recommended to perform serial determinations of estriol and HPL in the third trimester of pregnancy in all patients with histories indicative of fetal growth retardation and in those in whom the uterus appears small for date.     

Derivatives of apomorphine and of other N-substituted norapomorphines

Derivatives of apomorphine and of N-n-propylnorapomorphine were prepared to obtain modified pharmacological activity and enhanced chemical stability. Mouse profile and dog emesis screens were performed, and the activity of various N-substituted derivatives and their esters was evaluated and compared to the parent compounds. The N-n-propyl diacetate derivative and N-methyl and N-n-propyl ascorbate salts were remarkably stable to air: apomorphine etherate was no more stable than the free base. The dimers, the major products formed during the acid-catalyzed rearrangement of morphines to apomorphines, were all potent emetics. Additionally, two showed a significant antagonism to morphine in mice and dogs.     

Analysis of left ventricular wall movement during isovolumic relaxation and its relation to coronary artery disease

Left ventricular angiograms of 60 patients with ischaemic heart disease and 10 normal subjects were digitized frame by frame in order to study abnormalities of wall movement during the period of isovolumic relaxation. Plots were made of regional wall movement around the cavity throughout the cardiac cycle. In normal subjects 1-5 to 3-0 mm of symmetrical outward wall movement occurred during isovolumic relaxation, associated with an apparent increase of left ventricular volume of 10 +/- 4 per cent. The corresponding peak velocities of wall movement were 4-3 to 5-7 cm/s, significantly less than those recorded in the same region of the cavity after mitral valve opening. In patients with ischaemic heart disease, the following abnormalities were encountered: (1) Abnormal inward movement, which, in single coronary artery disease, occurred in the area supplied by the affected vessel. (2) Abnormal outward movement of more than 6 mm in non-affected areas which appeared to be a compensatory phenomenon. (3) An abnormal cavity shape change towards a more circular configuration before mitral valve opening. (4) Reduced peak rates of wall movement in affected areas during systole and filling. It is concluded that such inward wall movement during isovolumic relaxation is abnormal and a sign of local ischaemia whose presence has significant effects on overall left ventricular function in both systole and diastole.     

苍之流星——雷滋纳

1985年放映的《苍之流星SPT雷滋纳》背景设定为1996年的近未来（按当时来说）,由于当时正处在冷战时期,所以动画的设定中依然持续了这种局面（高桥怎么也没想到苏联在1990年解体了）,只不过是将地点从地球转移到了宇宙。作品的主题么,和高达差不多也属于反战一类的。不过和富野监督的作品比起来,《苍之流星SPT雷滋纳》的结局还是比较美满的,