Protein crystal growth in microgravity-temperature induced large scale crystallization of insulin

One of the major stumbling blocks that prevents rapid structure determination using x-ray crystallography is macromolecular crystal growth. There are many examples where crystallization takes longer than structure determination. In some cases, it is impossible to grow useful crystals on earth. Recent experiments conducted in conjunction with NASA on various Space Shuttle missions have demonstrated that protein crystals often grow larger and display better internal molecular order than their earth-grown counterparts. This paper reports results from three Shuttle flights using the Protein Crystallization Facility (PCF). The PCF hardware produced large, high-quality insulin crystals by using a temperature change as the sole means to affect protein solubility and thus, crystallization. The facility consists of cylinders/containers with volumes of 500, 200, 100, and 50 ml. Data from the three Shuttle flights demonstrated that larger, higher resolution crystals (as evidenced by x-ray diffraction data) were obtained from the microgravity experiments when compared to earth-grown crystals.     

Compensation of the bias caused by the wall filter on the mean Doppler frequency

In the presence of noise, any wall filter induces a bias on the mean Doppler frequency estimated by the algorithm based on the calculation of the phase of the autocorrelation function at lag 1. In this paper, it is shown that the bias results from the nonzero value of the autocorrelation function of the filtered noise at lag 1. A general method for compensating the bias was then deduced. It consists of a preliminary estimation of the filtered noise contribution and its subtraction from the autocorrelation function of the Doppler signal. The method is independent of the nature of the noise and wall filter. An evaluation of this method on simulated Doppler signals and on measurements from a moving-string phantom showed that effective compensation of the bias was obtained, but at the expense of a higher variance. Taking into account both the bias and the variance, however, it was shown that this method offers an improvement over the noncompensated method. Finally, the performance of this method was demonstrated using in vivo measurements taken from a human aorta.     

An investigation of 2'-deoxyribonucleoside cyanoboranes in mice for therapeutic safety

A standard acute toxicity study was undertaken to assess 2'-deoxyribonucleoside cyanoboranes for therapeutic safety. 2'-Deoxyribonucleoside cyanoboranes and related derivatives were nontoxic at doses required for anti-neoplastic and hypolipidemic activities. At higher doses (50 and 100 mg/kg/day IP for 7 days), all treated animals survived with slight reductions in total body weight and small decrements in daily food consumption. No clinical chemistry value was elevated to a magnitude suggesting onset of organ specific toxicity. However, agents appeared to modulate subpopulations of white blood cells, i.e., more lymphocytes than PMNs were present in blood from treated animals as determined by differential cell counts. This modulation is correlated with increases in granulomatous foci in the spleen and mesentery of treated animals after 7 days. The kidney was damaged only by Compound 5 at 50 and 100 mg/kg/day; Compound 5 had the most potent anti-neoplastic activity. The compounds demonstrated no in vitro toxicity against human HCT-8 ileum cells. LD(50) values were greater than 1000 mg/kg, IP, for all compounds.     

Antitumor Organometallics. IV. The Mutagenic Potential of Some Diphenylantimony(III) Dithiophosphorus Derivatives

Two diphenylantimony(III) derivatives of dithiophosphorus ligands, i.e. Ph(2)SbS(2)PPh(2) and Ph(2)SbS(2)P(OPr-i)(2), which were previously found to exhibit antitumor properties, have been now investigated for potential mutagenic effects in healthy and Ehrlich ascites tumor-bearing mice. Two short-term tests, i.e. the micronucleus test and the cytogenetic analysis, were used as end-points for mutagenicity. The results are consistent with a mutagenic potential for both organoantimony(III) compounds tested, the effect being higher for the phosphorodithioato derivative.     

Analysis of Multidrug Transporter in Living Cells. Inhibition of P-glycoprotein-mediated Efflux of Anthracyclines by Ionophores

One of the major obstacles of chemotherapy is that, after repeated treatments, cellular resistance to the drug appears. The problem is that the tumor cells become resistant not only to the drugs which have been used during the treatment but also to other drugs which are structurally and functionally unrelated. This is termed 'multidrug resistance' (MDR). MDR is frequently associated with decreased drug accumulation resulting from enhanced drug efflux. This is correlated with the presence of a membrane protein, P-glycoprotein, which pumps a wide variety of drugs out of cells thus reducing their toxicity. The search for molecules able to reverse MDR is very important. We here report that mobile ionophores such as valinomycin, nonactin, nigericin, monensin, calcimycin, lasalocid inhibit the efflux of anthracycline by P-glycoprotein whereas, channel-forming ionophores such as gramicidin do not. Cyclosporin which is also a strong Ca(2+) chelating agent also inhibits the P-glycoprotein-mediated efflux of anthracycline.     

Comments about the coincident bit counting (CBC) criterion for image registration

In a paper recently published (ibid., vol.12, p. 30-8, 1993), Chiang and Sullivan compare a new criterion for image registration called CBC (coincident bit counting) with two criteria that the authors proposed some years ago, namely SSC and DSC (stochastic and deterministic sign change criteria). The authors' nonparametric approach was demonstrated to outperform the conventional image registration criteria for robust registration in the fact that the value of their similarity measure did not take the specific pixel values into account. In light of this observation, Chiang and Sullivan have built the CBC criterion. The CBC method compares the number of coincident bits between the corresponding pixels in two different frames for a fixed amount of displacement. While the authors consider that the CBC is of interest and deserves to be studied, they feel that the comparison made by Chiang and Sullivan was not entirely accurate. Here the authors comment on this comparison and suggest possible further studies.