Equilibria of the anomeric and ring forms of ammonium 3-deoxy-d-manno-octulosonate in deuterium oxide

The tautomeric composition of a solution of ammonium 3-deoxy-d-manno-octulosonate (KDO, 1a) in D₂O at 28° was assessed by means of ¹³ C-F.t.-n.m.r. spectroscopy. The results revealed the presence of 6?0 and 11 % of the α and β anomers of the pyranose, and 20 and 9 % of the two furanoses, and suggested, but did not unequivocally prove, that the major furanose form is the α anomer. To facilitate interpretation of the spectral results for 1, ammonium 3,5-dideoxy-d-arabino(or ribo)-octulosonate (3a) was prepared by the reaction of 5-deoxy-d-erythro-pentose with sodium oxalacetate at pH 11. A chromatographically homogeneous, noncrystalline sample of 3 was obtained by lyophilization, and characterized as its (4-nitrophenyl)hydrazone (m.p. 162-163°). The ¹³C-n.m.r. spectrum of a solution of 3a in D₂O revealed it to be substantially all in the α-pyranose form. No signals were obtained for the possible 1,4-lactone of 3. As the 1,5-lactone and furanose forms are impossible for 3, it exhibited no signals analogous to those attributed to furanoid 1. On the basis of these results for 3, the two lactone forms of 1 were excluded from consideration, and the three pairs of ¹³C-n.m.r. signals observed at ≈45, 86, and 104 p.p.m. were assigned to the furanose forms of 1.     

A comparative cytopathologic study of noninvasive and invasive squamous cell carcinoma of the lung

Atypical cells and tissue fragments from the sputum of patients with early and advanced stages of squamous cell carcinoma of the bronchus are objectively characterized and quantitatively compared in this paper. Four classes of single-cell features of cytoplasm, nucleus, nucleolus and nuclear-cytoplasmic ratio are analyzed as a function of cell size and tumor development stage. Distinct differences in the cellular patterns are observed which may enhance cytologic discrimination between noninvasive and invasive stages of squamous cell carcinoma of the bronchus. Initial results justify the application of more sensitive measurement techniques (i.e., automated cytology) to an enlarged data base.     

Interferon Treatment of Ehrlich Ascites Tumor Cells: Effects on Exogenous mRNA Translation and tRNA Inactivation in the Cell Extract

We reported earlier that in cell extracts that were prepared from interferon-treated Ehrlich ascites tumor cells and preincubated and passed through Sephadex G-25 (S30_INT), the translation of exogenous mRNA (viral and host) was impaired and the impairment could be overcome to a large extent by adding a crude tRNA preparation from Ehrlich ascites tumor cells but not from Escherichia coli. We find now that the rate of inactivation of some tRNA's (especially those specific for leucine, lysine, and serine) but not those of many others is faster in S30_INT than in corresponding extracts from control cells. This increased rate of tRNA inactivation may perhaps account for the need for added RNA to overcome at least partially the impairment of translation in S30_INT. The relationship of the increased rate of tRNA inactivation to the antiviral effect of interferon is unclear. So far no significant difference has been detected in the amount of tRNA needed to overcome the impairment of encephalomyocarditis virus RNA translation in S30_INT between tRNA from interferon-treated cells and tRNA from control cells. Furthermore, no difference was found in the rate of inactivation in S30_INT between leucine-specific tRNA's from interferon-treated and from control cells. tRNA's specific for leucine and lysine were not inactivated (unless very slowly) during incubation under our conditions in an extract from interferon-treated (or from control) cells unless the extract had been passed through Sephadex G-25 or dialyzed. The translation of exogenous mRNA was, however, impaired in an extract from interferon-treated cells that had not been passed through Sephadex G-25. This impairment was apparently not overcome by added tRNA.     

Synthesis and degradation of proteins during wheat endosperm development

Synthesis of proteins rich in lysine declines progressively with endosperm development and these proteins appear to be degraded preferentially at later stages. The proteolytic enzymes in extracts of endosperms at a late stage of development release considerably more lysine radioactivity from labelled endosperm proteins as compared with the enzymes in endosperms at an early stage.     

Role of doxapram in reducing pulmonary complications after major surgery.

In a double-blind study patients given a single dose of doxapram 1-5-2-0 mg/kg combined with morphine postoperatively had a significantly lower incidence of reflex postoperative cough and expectoration of purulent sputum than patients given morphine alone. They also had significantly higher arterial oxygen tensions five days postoperatively. Smaller differences were found with naloxone combined with morphine.     

Some observations on the biology of Cirrhinus reba (Cuvier)

Some observations on the biology of Cirrhinus reba (Cuvier) from Muzaffarnagar (U.P., India) have been made during the period July 1966 to June 1969. In C. reba both males and females mature simultaneously. The gonads attain the maximum weight in June and minimum in November. There is a definite seasonal cycle in relative condition. The relative condition in both male and female is highest in June preceeding the period of breeding. It is the gonad weight which influences the fluctuations of the relative condition. The visceral weight does not exert any significant effect on it. It is found possible to determine the spawning season and its extent, from the seasonal fluctuations of the relative condition. The present studies have also thrown light on the maturation and spawning habits of C. reba . The fish has only one spawning season of short duration, running from July to early September. In a mature ovary, the mature ova form only one mode which is sharply distinguished from the immature stock.     

Increasing reproducibility,robustness, and generalizability of biomarker selection from meta-analysis using Bayesian methodology

A major limitation of gene expression biomarker studies is that they are not reproducible as they simply do not generalize to larger, real-world, heterogeneous populations. Frequentist multi-cohort gene expression meta-analysis has been frequently used as a solution to this problem to identify biomarkers that are truly differentially expressed. However, the frequentist meta-analysis framework has its limitations–it needs at least 4–5 datasets with hundreds of samples, is prone to confounding from outliers and relies on multiple-hypothesis corrected p-values. To address these shortcomings, we have created a Bayesian meta-analysis framework for the analysis of gene expression data. Using real-world data from three different diseases, we show that the Bayesian method is more robust to outliers, creates more informative estimates of between-study heterogeneity, reduces the number of false positive and false negative biomarkers and selects more generalizable biomarkers with less data. We have compared the Bayesian framework to a previously published frequentist framework and have developed a publicly available R package for use.