High genomic deleterious mutation rates in hominids

It has been suggested that humans may suffer a high genomic deleterious mutation rate. Here we test this hypothesis by applying a variant of a molecular approach to estimate the deleterious mutation rate in hominids from the level of selective constraint in DNA sequences. Under conservative assumptions, we estimate that an average of 4.2 amino-acid-altering mutations per diploid per generation have occurred in the human lineage since humans separated from chimpanzees. Of these mutations, we estimate that at least 38% have been eliminated by natural selection, indicating that there have been more than 1.6 new deleterious mutations per diploid genome per generation. Thus, the deleterious mutation rate specific to protein-coding sequences alone is close to the upper limit tolerable by a species such as humans that has a low reproductive rate, indicating that the effects of deleterious mutations may have combined synergistically. Furthermore, the level of selective constraint in hominid protein-coding sequences is atypically low. A large number of slightly deleterious mutations may therefore have become fixed in hominid lineages.     

Model multiple antigenic and homopolymeric peptides from non-repetitive sequences of malaria merozoite proteins elicit biologically irrelevant antibodies

We describe here a new type of mitochondrial mutation (dum24; for dark uniparental minus inheritance) of the unicellular photosynthetic alga Chlamydomonas reinhardtii. The mutant fails to grow under heterotrophic conditions and displays reduced growth under both photoautotrophic and mixotrophic conditions. In reciprocal crosses between mutant and wild-type cells, the meiotic progeny only inherit the phenotype of the mating-type minus parent, indicating that the dum24 mutation exclusively affects the mitochondrial genome. Digestion with various restriction enzymes followed by DNA gel blot hybridizations with specific probes demonstrated that dum24 cells contain four types of altered mitochondrial genomes: deleted monomers lacking cob, nd4, and the 3' end of the nd5 gene; deleted monomers deprived of cob, nd4, nd5, and the 5' end of the cox1 coding sequence; and two types of dimers produced by end-to-end fusions between monomers similarly or differently deleted. Due to these mitochondrial DNA alterations, complex I activity, the cytochrome pathway of respiration, and presumably, the three phosphorylation sites associated with these enzyme activities are lacking in the mutant. The low respiratory rate of the dum24 cells results from the activities of rotenone-resistant NADH dehydrogenase, complex II, and alternative oxidase, with none of these enzymes being coupled to ATP production. To our knowledge, this type of mitochondrial mutation has never been described for photosynthetic organisms or more generally for obligate aerobes.     

Measurement of the Thermophysical Properties of a Thermoplastic Ceramic Paste Across its Solidification Range Using Power-Compensated Differential Scanning Calorimeter

The specific heat capacity, thermal conductivity, and thermal diffusivity of a thermoplastic ceramic paste were investigated on a power-compensated, differential scanning calorimeter (DSC) using the heat capacity spectral analysis method developed by Merzlyakov and Schick for measuring these parameters on low thermal conductivity solids. The paste features an ultra-fine zinc oxide powder (a number-length mean diameter, D _1,0, of 85 nm) as the discrete phase, and a thermoplastic continuous phase comprising a blend of organic waxes with a melting range of ca. 30°–70°C. This paste is formulated with a solids loading of 50 vol% and is currently used in a novel continuous casting process to manufacture pharmaceutical products. The properties of the paste were investigated over a temperature range encompassing the melt and solid states, and for solid loadings from 0 to 70 vol%. The results compare favorably with those obtained using transient line source and transient plane methods.     

Massive hemorrhage caused by a perforating Gianturco-Z stent resulting in an aortoesophageal fistula

Squamous cell carcinoma of the tonsil has a relatively poor prognosis. Aggressive surgery, radiation therapy and combinations of irradiation and surgery have been employed but there exists some controversy about the efficacy of these treatment modalities. The purpose of this paper is to compare the efficacy of treatment between the surgery followed by radiation therapy and the preoperative radiation therapy followed by surgical resection. The medical records of 33 patients treated for squamous cell carcinoma of the tonsil at the Department of Otolaryngology-Head and Neck Surgery, Korea University Hospital between 1989-1993 were reviewed retrospectively. None of the patients were stage I, but stage II, III, and IV were four, five, and 24 patients, respectively. There were 30 males and three females. The most common histopathology was moderately differentiated squamous cell carcinoma (20/33). The 13 patients treated initially with surgery had an overall three-year survival rate of 38.5%, and the rate for the 20 patients treated initially with radiation was 40%. The main pattern of treatment failure was a local recurrence and neck metastases, and pathologic differentiation thought to be an important prognostic factor. Complications are fewer in patients treated initially with surgery (23.1%) than patients initially treated with radiation (50.0%). There is no difference in the efficacy between the two therapeutic groups.     

Simplified Inelastic Design of Steel Girder Bridges

Inelastic design of steel girder bridges can result in beneficial material and fabrication cost savings and reduce the susceptibility of steel girder bridges to fatigue. The ability to redistribute large negative region moments, coupled with section capacities exceeding the yield moment, results in an efficient structure used to its limit-state capacity. Proposed LRFD inelastic design provisions are presented that allow compact or noncompact pier sections resulting in consistent bridge design across the steel girder bridge inventory. This paper illustrates the simplified inelastic design provisions, presents an example design of a two-span composite bridge comprising noncompact sections at the pier, and summarizes the experimental verification of the example design. The proposed inelastic design procedures are simple to apply, removing the cumbersome continuity and iterative requirements of past inelastic design practice.     

Use of flavored cigarettes among older adolescent and adult smokers: United States, 2004--2005

Cigarettes with candy, fruit and alcohol flavors have been introduced in recent years as extensions to popular cigarette brands, raising concerns in the public health community that the enticing names, creative packaging, and intense flavorings of these products may be especially appealing to youth. This study used two national surveys to examine the prevalence of use of Camel Exotic Blends, Kool Smooth Fusion, and Salem Silver Label brands during 2004--2005 among older adolescents and young adult smokers aged 17-26 years and adult smokers aged > or =25 years. Overall use of any of these flavored brands in the past 30 days was 11.9% among smokers aged 17-26 years and 6.7% among smokers aged > or =25 years. A significant gradient in use was seen across age, with the highest rates of utilization among 17-year-old (22.8%) and 18-19-year-old smokers (21.7%) (p<.001). Uniquely flavored cigarette brands seem to be most attractive to the youngest smokers and should be prohibited.