Exceptional convergent evolution in a virus

Replicate lineages of the bacteriophage phiX 174 adapted to growth at high temperature on either of two hosts exhibited high rates of identical, independent substitutions. Typically, a dozen or more substitutions accumulated in the 5.4-kilobase genome during propagation. Across the entire data set of nine lineages, 119 independent substitutions occurred at 68 nucleotide sites. Over half of these substitutions, accounting for one third of the sites, were identical with substitutions in other lineages. Some convergent substitutions were specific to the host used for phage propagation, but others occurred across both hosts. Continued adaptation of an evolved phage at high temperature, but on the other host, led to additional changes that included reversions of previous substitutions. Phylogenetic reconstruction using the complete genome sequence not only failed to recover the correct evolutionary history because of these convergent changes, but the true history was rejected as being a significantly inferior fit to the data. Replicate lineages subjected to similar environmental challenges showed similar rates of substitution and similar rates of fitness improvement across corresponding times of adaptation. Substitution rates and fitness improvements were higher during the initial period of adaptation than during a later period, except when the host was changed.     

TGF-beta mediated G1 arrest in a human melanoma cell line lacking p15INK4B: evidence for cooperation between p21Cip1/WAF1 and p27Kip1

We have studied TGF-beta mediated G1 arrest in WM35, an early stage human melanoma cell line. These cells have lost p15INK4B expression through loss of one chromosome 9 and rearrangement of the other. In asynchronously growing WM35, TGF-beta caused reductions in cyclin D1, cyclin A and cdk4 proteins and their associated kinase activities and an increase in both p21Cip1/WAF1 and p27Kip1. These findings were confirmed in cells released from quiescence in the presence of TGF-beta, in which TGF-beta inhibited or delayed the reduction in the cdk inhibitors that normally occurs in late G1. In contrast to observations in other cell types, there was an increased association of both p21Cip1/WAF1 and p27Kip1 with cyclin D1/cdk4 and with cyclin E/cdk2 during TGF-beta mediated arrest of asynchronously growing cells. Upregulation of p21Cip1/WAF1 preceded that of p27Kip1. Furthermore, p21Cip1/WAF1 and p27Kip1 were not present in the same cdk complexes but bound distinct populations of target cdk molecules. Both p21Cip1/WAF1 and p27Kip1 immunoprecipitates from asynchronously growing cells contained active kinase complexes. These KIP-associated kinase activities were reduced in TGF-beta arrested cells. It has been proposed that in TGF-beta arrested epithelial cells, up-regulation of p15INK4B and of p15INK4B binding to cdk4 serves to destabilize the association of p27Kip1 with cyclin D1/cdk4, promoting p27Kip1 binding and inhibition of cyclin E/cdk2. Our findings demonstrate that this is not a universal mechanism of G1 arrest by TGF-beta. In TGF-beta arrested WM35, which lack p15INK4B, the increased p21Cip1/WAF1 may serve a similar function to that of p15INK4B: initiating kinase inhibition and providing an additional mechanism to supplement the effect of p27Kip1 on G1 cyclin/cdks.     

Visceral leishmaniasis: II. Histiocyte ultrastructure in bone marrow associated with low level of parasitaemia and mimicking malignant histiocytosis

The ultrastructural features of histiocytes in the bone marrow (BM) were studied in a febrile, splenomegalic and pancytopenic Sudanese patient who was diagnosed by one of us as visceral leishmaniasis (VL) associated with low level of parasitaemia and mimicking malignant histiocytosis (MH). Serial thick (STS) and ultrathin (SUT) sections showed that the BM was hypercellular and markedly infiltrated by large histiocytes with prominent phagocytosis. A thorough examination of various ST and UT section revealed only a single, typical Leishman-Donovan body. At transmission electron microscopy (TEM) level, two principal types of histiocytic cells were identified: Type I, subdivided into two subtypes, were actively phagocytic histiocytes (PH) with large digestive vacuoles and primary lysosomes; type II were nonphagocytic histiocytes (nPH) with primary lysosomes only. The rate of PH to nPH ws 7:2 in plastic STS. The interaction between the PH and ingested cells is described. Both types of cell were morphologically similar to previously described malignant histiocytic cells. However, this study showed a better characterization of PH during VL.     

Colposacropexy: an alternative technique

Colposacropexy procedures restore anatomically correct apical vaginal support on the levator plate at the ischial spine level. Venous hemorrhage resulting from laceration of presacral veins during suture fixation is the major hazard of this procedure. Titanium orthopedic bone anchor fixation minimizes this risk through precision placement of the bone anchor-suture unit.     

Electromagnetic Resistive Drift Instability in Current Carrying Low Temperature Tokamak Edges

It is shown that the purely growing electrostatic rippling mode can couple with the shear Alfven wave to give rise to an oscillatory electromagnetic instability in tokamak edge regions. This mechanism can be one of the causes of electromagnetic fluctuations observed near plasma edges. This instability can occur only in the very low temperature regions where resistivity fluctuations can become important due to large electron-ion collision frequency.     

Low-loss high power RF switching using multifinger AlGaN/GaN MOSHFETs

We demonstrate a novel RF switch based on a multifinger AlGaN/GaN MOSHFET. Record high saturation current and breakdown voltage, extremely low gate leakage current and low gate capacitance of the III-N MOSHFETs make them excellent active elements for RF switching. Using a single element test circuit with 1-mm wide multifinger MOSHFET we achieved 0.27 dB insertion loss and more than 40 dB isolation. These parameters can be further improved by impedance matching and by using submicron gate devices. The maximum switching power extrapolated from the results for 1A/mm 100 /spl mu/m wide device exceeds 40 W for a 1-mm wide 2-A/mm MOSHFET.     

The optimisation of higher order resampling methods in a multiprocessor environment

The processing of images obtained from satellites often involves highly repetitive calculations on very large amounts of data. This processing is extremely time consuming when these calculations are performed on sequential machines. Parallel computers are well suited to handling computationally expensive operations such as higher order interpolations on large data sets. This paper decribes work undertaken to develop parallel implementations of a set of resampling procedures on an Alliant VFX/4. Each resampling procedure implemented has been optimised in three stages. First, the algorithm has been restructured, where two-dimensional resampling is performed by two one-dimensional resampling operations. Second, each procedure has been reprogrammed in such a way that the autoparallelisation provided by the FX/Fortran compiler has been exploited. Thirdly, data dependent analysis of each procedure has been performed in order to achieve full optimization of each procedure; each procedure has been restructured where appropriate to circumvent vectorisation and concurrency inhibiting data dependencies. The nature and extent of the code optimization achieved for each procedure is presented in this paper. The original code for the most computationally expensive procedure, as targeted at a sequential machine, was found to have an execution time of 4900 seconds on the Alliant VFX/4 when compiled with regular compiler optimization options. Following algorithmic redesigning and reprogramming of the code, as indicated in stage 1 and stage 2, the execution time was reduced to 248 seconds. Restructuring of the code following data dependency analysis indicated in stage 3 in order to avoid data dependencies and allow concurrency and vectorisation, further reduced execution time to 162 seconds. The consequence of this work is that higher-order resampling methods which had not previous been practical are now routinely performed on the Alliant VFX/4 at the University of Dundee.