A genetic algorithm for multiple molecular sequence alignment

MOTIVATION: Multiple molecular sequence alignment is among the most important and most challenging tasks in computational biology. The currently used alignment techniques are characterized by great computational complexity, which prevents their wider use. This research is aimed at developing a new technique for efficient multiple sequence alignment. APPROACH: The new method is based on genetic algorithms. Genetic algorithms are stochastic approaches for efficient and robust searching. By converting biomolecular sequence alignment into a problem of searching for optimal or near-optimal points in an 'alignment space', a genetic algorithm can be used to find good alignments very efficiently. RESULTS: Experiments on real data sets have shown that the average computing time of this technique may be two or three orders lower than that of a technique based on pairwise dynamic programming, while the alignment qualities are very similar. AVAILABILITY: A C program on UNIX has been written to implement the technique. It is available on request from the authors.     

A new erasing method for a single-voltage long-endurance flashmemory

A new method to erase a standard (double-poly, stacked-gate NOR-type) flash cell is proposed. The method, still using the tunneling mechanism to extract electrons from the floating gate, is based on the concept of keeping the electric field constant during the whole erasing operation. The new method has two main advantages with respect to the conventional one: (1) it does not depend on the supply voltage variation and (2) it allows a better reliability in terms of endurance-induced stress. Results have shown that flash device performances are greatly improved in terms of stability and endurance reliability up to one million cycles     

Ultralow-voltage boron-doped diamond field emitter vacuum diode

A boron-doped diamond field emitter diode with ultralow turn-on voltage and high emission current is reported. The diamond field emitter diode structure with a built-in cap was fabricated using molds and electrostatic bonding techniques. The emission current versus anode voltage of the capped diamond emitter diode with boron doping, sp² content, and vacuum thermal electric (VTE) treatment shows a very low turn-on voltage of 2 V. A high emission current of 1 μA at an anode voltage of less than 10 V can be obtained from a single diamond tip. The turn-on voltage is significantly lower than comparable silicon field emitters     

往复式压缩机管道的防振设计

分析了往复式压缩机管道产生振动的原因及影响因素,提出解决管道振动的方法及对策。     

Treatment of the sequelae of enucleation by septal chondro-mucosal composite graft. Report of 21 cases]

Enucleation frequently and progressively causes an enophtalmus and atrophia of the inferior eyelid, thereby leading to a height deficiency. Buccal mucous grafts give rise to phenomena such as secondary retraction. This may have complex and painful post-operative outcomes. However, when a septal chondromucous graft is performed, the height in the inferior palpebral part becomes more aesthetic, more retentive and quickly allows the wearing of a more voluminous prosthesis. Thus, the notinable enophtalmus can be corrected and the aesthetic quality of the looking is substantially restored. The authors report this surgical procedure and the results obtained with 21 patients which appear to be particularly promising.     

Solution structure of a DNA duplex containing the exocyclic lesion 3,N4-etheno-2'-deoxycytidine opposite 2'-deoxyguanosine

Vinyl chloride reacts with cellular DNA producing 3,N4-etheno-2'-deoxycytidine (epsilonC) along with other exocyclic adducts. The solution structure of an oligodeoxynucleotide duplex containing an epsilonC.dG base pair was determined by high-resolution NMR spectroscopy and molecular dynamics simulations. NMR data indicated that the duplex adopts a right-handed helical structure having all residues in anti orientation around the glycosylic torsion angle. The epsilonC adduct has a sugar pucker in the C3'-endo/C4'-exo region while the rest of the residues are in the C2'-endo/C3'-exo range. NOE interactions established Watson-Crick alignments for canonical base pairs of the duplex. The imino proton of the lesion-containing base pair resonated as a sharp signal that was resistant to water exchange, suggesting hydrogen bonding. Restrained molecular dynamics simulations generated three-dimensional models in excellent agreement with the spectroscopic data. The refined structures are slightly bent at the lesion site without major perturbations of the sugar-phosphate backbone. The adduct is displaced and shifted toward the major groove of the helix while its partner on the complementary strand remains stacked. The epsilonC(anti).dG(anti) base pair alignment is sheared and stabilized by the formation of hydrogen bonds. The biological implications of structures of epsilonC-containing DNA duplexes are discussed.     

Accuracy of using computed tomography to identify pedicle screw placement in cadaveric human lumbar spine

STUDY DESIGN: Utility of using computed tomography to predict pedicle screw misplacement. OBJECTIVE: This study defines the sensitivity and specificity of predicting pedicle screw placement by experienced clinicians using a CT scan image. SUMMARY OF BACKGROUND DATA: In clinical and research settings, the method most commonly used to evaluate pedicle screws placement has been computed tomography. However, no current literature describes the accuracy of this method of evaluating screw placement. METHOD: Cobalt-chrome and titanium alloy pedicle screws of identical size were placed in six cadaveric human lumbar spine. Wide laminectomy was performed to allow complete visualization of the pedicles. Three consecutive lumbar levels were instrumented in each spine, giving 36 pedicle screw placements to identify. The instrumented spines were imaged, and four orthopaedic spine surgeons and a musculoskeletal radiologist were asked to read the images to identify the accuracy of screw placement within the pedicles. RESULTS: The sensitivity rate of identifying a misplaced screw was 67 +/- 6% for cobalt-chrome screws compared with 86 +/- 5% for titanium screws (P < 0.005). The specificity rates of radiographic diagnosis of misplaced pedicle screws were 66 +/- 10% for cobalt-chrome screws and 88 +/- 8% for titanium screws (P < 0.005). Similarly, a statistically significant difference was found in the sensitivity rates of identifying screws placed correctly in the pedicle: 70 +/- 10% for cobalt-chrome screws versus 89 +/- 8% for titanium screws (P < 0.005). Overall accuracy rates were 68 +/- 7% for cobalt chrome screws versus 87 +/- 3% for titanium screws (P < 0.002). CONCLUSION: Reliance on the computed tomography scan data alone in determining accuracy of pedicle screws can lead to inaccuracies in both clinical and research conditions.     

Diversity of pituitary cells in primary cell culture. An immunocytochemical study

A bioassay system for rapid detection of carcinogenic agents has been developed using male Fischer 344 rats to bridge the gap between long-term carcinogenicity tests and short-term screening assays. The system, called the medium-term liver bioassay, is fundamentally based on the 2-stage hypothesis of tumor production, employing initiation by diethylnitrosamine (200 mg/kg, i.p.) in the first stage and test chemical administration during the second, in combination with two-thirds partial hepatectomy. It requires only 8 wk for animal experimentation and a further few weeks for quantitative analysis of immunohistochemically demonstrated glutathione S-transferase placental form positive hepatic foci. A total of 291 chemicals/substances have already been analyzed in our laboratory. Among 63 chemicals that were proved to be carcinogenic in the liver of rat and/or mouse, 57 (90%) gave positive results irrespective of their mutagenicity. Negative compounds include peroxisome proliferators and tamoxifen. Even nonhepatocarcinogens were positive at a rate of 24%. Eighty-six percent (12/14) of mouse liver carcinogens were also positive. On the other hand, only 2 out of 45 noncarcinogens showed very weak positivity. Thus, the efficacy of the system for hepatocarcinogens has been well established. This bioassay is increasingly regarded as an appropriate alternative test for carcinogenicity risk assessment and is practically used for a rapid evaluation of hepatocarcinogenicity of chemicals.     

The crystal structure of HIV-1 Nef protein bound to the Fyn kinase SH3 domain suggests a role for this complex in altered T cell receptor signaling

BACKGROUND: Human immunodeficiency virus (HIV) Nef protein accelerates virulent progression of acquired immunodeficiency syndrome (AIDS) by its interaction with specific cellular proteins involved in signal transduction and host cell activation. Nef has been shown to bind specifically to a subset of the Src family of kinases. The structures of free Nef and Nef bound to Src homology region 3 (SH3) domain are important for the elucidation of how the affinity and specificity for the Src kinase family SH3 domains are achieved, and also for the development of potential drugs and vaccines against AIDS. RESULTS: We have determined the crystal structures of the conserved core of HIV-1 Nef protein alone and in complex with the wild-type SH3 domain of the p59fyn protein tyrosine kinase (Fyn), at 3.0 A resolution. Comparison of the bound and unbound Nef structures revealed that a proline-rich motif (Pro-x-x-Pro), which is implicated in SH3 binding, is partially disordered in the absence of the binding partner; this motif only fully adopts a left-handed polyproline type II helix conformation upon complex formation with the Fyn SH3 domain. In addition, the structures show how an arginine residue (Arg77) of Nef interacts with Asp 100 of the so-called RT loop within the Fyn SH3 domain, and triggers a hydrogen-bond rearrangement which allows the loop to adapt to complement the Nef surface. The Arg96 residue of the Fyn SH3 domain is specifically accommodated in the same hydrophobic pocket of Nef as the isoleucine residue of a previously described Fyn SH3 (Arg96-->lle) mutant that binds to Nef with higher affinity than the wild type. CONCLUSIONS: The three-dimensional structures support evidence that the Nef-Fyn complex forms in vivo and may have a crucial role in the T cell perturbating action of Nef by altering T cell receptor signaling. The structures of bound and unbound Nef reveal that the multivalency of SH3 binding may be achieved by a ligand induced flexibility in the RT loop. The structures suggest possible targets for the design of inhibitors which specifically block Nef-SH3 interactions.