Synthesis of Aminopyridazines from Aminocyclopropenylium Salts and Diazomethyl Compounds [1]

Amino-substituted cyclopropenylium salts ( 11a,b ) react with diazomethyl compounds ( 12a-i ) in dichloromethane or acetonitrile in the presence of a base (ethyldiisopropylamine, 1,5-diazabicyclo[4.3.0] non-5-ene) to form 4-aminopyridazines ( 13a-i ) specifically. The reaction is interpreted in terms of an initial electrophilic diazoalkane substitution to give diazomethylcyclopropenes ( 11 + 12 → 14 ) which undergo a [1.5]-cyclisation to form the betaines 16 which, in turn, isomerise with opening of the bridging bond to give the aminopyridazines 13 . In a similar manner, the tris[amino] cyclopropenylium salts 8a,b and 10a-c are converted to the 3,4,5-tris[amino]-pyridazines ( 21a-k ) by treatment with diazomethyl compounds ( 12a, c-f ).     

Tumor size and prognosis in aggressively treated osteosarcoma

PURPOSE: The aim of this retrospective analysis was to investigate the prognostic significance and optimal measures of tumor size in osteosarcoma treated with intensive neoadjuvant chemotherapy. PATIENTS AND METHODS: Initial anterior-posterior (AP) and lateral x-ray films of 128 patients treated within the trials Cooperative Osteosarcoma Study (COSS)-80, -82, and -86, were evaluated for the following three tumor diameters: length, width, and depth. Metastasis-free survival (MFS) analyses were performed in univariate and multivariate models with one, two, and three dimensions of the tumor as absolute or relative measures (tumor length, referred to bone length, plane and volume to body-surface area). RESULTS: Univariate analyses of MFS showed a high prognostic significance of all absolute measures. Relative measures, at best, showed a comparable predictive value. Cox regression analysis indicated the high prognostic significance of absolute tumor volume (ATV; P < .0001) and histologic response (P < .0001). None of 19 patients with an ATV < or = 70 cm3 and only four of 53 with an ATV < or = 150 cm3 relapsed, while in patients with an ATV more than 150 cm3, the relapse rate remained 40% to 60%, irrespective of further increase in volume. CONCLUSION: Initial tumor size is an important and easily obtainable prognostic factor in osteosarcoma and may serve as a basis for risk-adapted therapy. It is best represented by the absolute three-dimensional measure ATV. There is a cut-off point regarding the incidence of metastases at a tumor volume of approximately 150 cm3 as calculated from two-plane x-ray films.     

Alkali silica reactivity of agglomerated silica fume

It is commonly accepted that replacement of a portion of cement in mortar or concrete with well-dispersed silica fume reduces expansion caused by alkali silica reaction. Recently there has been much discussion that large, agglomerated particles of silica fume may actually act as alkali silica reactive aggregates, thereby increasing expansion rather than reducing it. The data in the literature, from both field and laboratory studies, are inconsistent. This prompted an extensive laboratory investigation into the alkali silica reactivity of silica fume. Results from accelerated expansion testing and microscopic investigations are presented. It was seen that some agglomerated silica fumes participate in ASR while others do not. Factors determining the reactivity of silica fume agglomerates are suggested.     

Ion-dipole interactions between adsorbed CO and support cations in Pt/K-LTL

The adsorption of carbon monoxide on a non-acidic Pt/K-LTL catalyst has been studied by diffuse reflectance and transmission IR spectroscopy. The CO spectrum is strongly dependent on the experimental conditions. Adsorption on the small Pt clusters in the presence of water gives linear-CO bands between 2060 and 1990 cm^–1 and a bridging-CO band around 1800 cm^–1. In the absence of water, the linear bands are red shifted to about 1940 and 1720 cm^–1, respectively. The frequency shift is attributed to an ion-dipole interaction between adsorbed CO and support cations. The ion-dipole interaction is screened by the adsorbed water leading to a smaller red shift in the CO stretching frequency.     

Impact damage detection in carbon fibre composites using HTS SQUIDs and neural networks

A neural network-based data analysis tool, developed to speed the damage detection process for the NDE of impact damaged carbon fibre composites, is discussed. A feature extraction method utilising a gradient threshold search function and a feed forward neural network for pattern recognition were used to develop the system. Impact damaged carbon composite sample plates were scanned with an eddy current-based NDE setup using HTS SQUID gradiometers and double-D excitation coils. Detection of damage sites in data affected by noise spikes caused by environmental disturbances is demonstrated. Finally, a possible design for a future entirely automated scanning system is also introduced.     

Use of neural networks for predictions using time series: Illustration with the El Niño Southern oscillation phenomenon

This paper introduces the use of sets of multiple networks (bundled networks) to manage the variability due to different initialization parameters. This method makes it statistically impossible for the networks to be trapped in the same local minimum, and therefore allows better control of the confidence of the prediction eventually given. The spread of the forecasts given by these different networks can be used for prediction reliability purposes. An illustration of this usage is given with the El Niño phenomenon.     

Hand function related to age and sex

After adapting Jebssen's Test of Hand Function to Australian conditions, this study investigated his claim of no significant difference in hand performance among participants younger than 60 years, and determined whether age might be a factor when associated with sex. The method was to test 383 subjects of both sexes in 6 age groups. A 2-factor analysis with age and sex as factors yielded significant differences (p less than 0.01) for "grip strength" "manipulating small objects," and "moving large heavy objects," and indications of significance (p less than 0.05) for "card turning" and "moving large light objects." The sex factor showed males to be significantly better "grip strength," in "moving large heavy objects," and "large light objects," except in the 66-99 age interval where females were significantly better on teh last 2 variables. Females performed better on "writing" and were generally better in "manipulating small objects." These results suggest that the one set of norms given by Jebsen for 60 years and less for each sex, should be replaced by 5 or more, even though the differences were quite small when standard deviations were considered.     

Human C-peptide. Part I: Radioimmunoassay

Synthetic human C-peptide bearing a Tyrosine group at its amino end is labelled with 125iodine using chloramin T or hydrogen peroxide and lactoperoxidase. The results are compared applying both methods. Antiserum to synthetic human C-peptide (without Tyrosine) which was partially compared to rabbit albumin, is raised in guinea pigs and goats. Goats show to be superior to guinea pigs concerning antibody production. The so-called "hook effect" phenomenon is observed in setting up the standard curves for the radioimmunoassay. Monotonically decreasing standard curves are obtained on dilution of antiserum with a high antibody titer which was produced by repeated immunization in goats. Free C-peptide and C-peptide bound to antiserum are separated with the anxion exchange resin Amberlite. Using this separation technique we excluded unspecific binding of labelled C-peptide to protein fractions in serum of diabetics. The sensitivity of our radioimmunoassay is approx. 0.3 ng C-peptide/ml serum. Intra- and interassay variability are below 10%. Human proinsulin is the only substance found to crossreact with the antiserum.     

Effect of Lowering Asymmetric Dimethylarginine (ADMA) on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal Mass

The purpose of the work was to study the impact of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) and its degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH1), on atherosclerosis in subtotally nephrectomized (SNX) ApoE-deficient mice. Male DDAH1 transgenic mice (TG, n = 39) and C57Bl/6J wild-type littermates (WT, n = 27) with or without the deletion of the ApoE gene underwent SNX at the age of eight weeks. Animals were sacrificed at 12 months of age, and blood chemistry, as well as the extent of atherosclerosis within the entire aorta were analyzed. Sham treated (no renal mass reduction) ApoE-competent DDAH1 transgenic and wild-type littermates (n = 11) served as a control group. Overexpression of DDAH1 was associated with significantly lower ADMA levels in all treatment groups. Surprisingly, SNX mice did not exhibit higher ADMA levels compared to sham treated control mice. Furthermore, the degree of atherosclerosis in ApoE-deficient mice with SNX was similar in mice with or without overexpression of DDAH1. Overexpression of the ADMA degrading enzyme, DDAH1, did not ameliorate atherosclerosis in ApoE-deficient SNX mice. Furthermore, SNX in mice had no impact on ADMA levels, suggesting a minor role of this molecule in chronic kidney disease (CKD) in this mouse model.