Trends in lipoplex physical properties dependent on cationic lipid structure, vehicle and complexation procedure do not correlate with biological activity

Using a group of structurally related cytofectins, the effects of different vehicle constituents and mixing techniques on the physical properties and biological activity of lipoplexes were systematically examined. Physical properties were examined using a combination of dye accessibility assays, centrifugation, gel electrophoresis and dynamic light scattering. Biological activity was examined using in vitro transfection. Lipoplexes were formulated using two injection vehicles commonly used for in vivo delivery (PBS pH 7.2 and 0.9% saline), and a sodium phosphate vehicle previously shown to enhance the biological activity of naked pDNA and lipoplex formulations. Phosphate was found to be unique in its effect on lipoplexes. Specifically, the accessible pDNA in lipoplexes formulated with cytofectins containing a γ-amine substitution in the headgroup was dependent on alkyl side chain length and sodium phosphate concentration, but the same effects were not observed when using cytofectins containing a β-OH headgroup substitution. The physicochemical features of the phosphate anion, which give rise to this effect in γ-amine cytofectins, were deduced using a series of phosphate analogs. The effects of the formulation vehicle on transfection were found to be cell type-dependent; however, of the formulation variables examined, the liposome/pDNA mixing method had the greatest effect on transgene expression in vitro. Thus, though predictive physical structure relationships involving the vehicle and cytofectin components of the lipoplex were uncovered, they did not extrapolate to trends in biological activity.

Long term trends in the evolution of H(3) HA1 human influenza type A

We have studied the HA1 domain of 254 human influenza A(H3N2) virus genes for clues that might help identify characteristics of hemagglutinins (HAs) of circulating strains that are predictive of that strain’s epidemic potential. Our preliminary findings include the following. (i) The most parsimonious tree found requires 1,260 substitutions of which 712 are silent and 548 are replacement substitutions. (ii) The HA1 portion of the HA gene is evolving at a rate of 5.7 nucleotide substitutions/year or 5.7 × 10−3 substitutions/site per year. (iii) The replacement substitutions are distributed randomly across the three positions of the codon when allowance is made for the number of ways each codon can change the encoded amino acid. (iv) The replacement substitutions are not distributed randomly over the branches of the tree, there being 2.2 times more changes per tip branch than for non-tip branches. This result is independent of how the virus was amplified (egg grown or kidney cell grown) prior to sequencing or if sequencing was carried out directly on the original clinical specimen by PCR. (v) These excess changes on the tip branches are probably the result of a bias in the choice of strains to sequence and the detection of deleterious mutations that had not yet been removed by negative selection. (vi) There are six hypervariable codons accumulating replacement substitutions at an average rate that is 7.2 times that of the other varied codons. (vii) The number of variable codons in the trunk branches (the winners of the competitive race against the immune system) is 47 ± 5, significantly fewer than in the twigs (90 ± 7), which in turn is significantly fewer variable codons than in tip branches (175 ± 8). (viii) A minimum of one of every 12 branches has nodes at opposite ends representing viruses that reside on different continents. This is, however, no more than would be expected if one were to randomly reassign the continent of origin of the isolates. (ix) Of 99 codons with at least four mutations, 31 have ratios of non-silent to silent changes with probabilities less than 0.05 of occurring by chance, and 14 of those have probabilities <0.005. These observations strongly support positive Darwinian selection. We suggest that the small number of variable positions along the successful trunk lineage, together with knowledge of the codons that have shown positive selection, may provide clues that permit an improved prediction of which strains will cause epidemics and therefore should be used for vaccine production.

Toward a new synthesis: Major evolutionary trends in the angiosperm fossil record

Angiosperm paleobotany has widened its horizons, incorporated new techniques, developed new databases, and accepted new questions that can now focus on the evolution of the group. The fossil record of early flowering plants is now playing an active role in addressing questions of angiosperm phylogeny, angiosperm origins, and angiosperm radiations. Three basic nodes of angiosperm radiations are identified: (i) the closed carpel and showy radially symmetrical flower, (ii) the bilateral flower, and (iii) fleshy fruits and nutritious nuts and seeds. These are all coevolutionary events and spread out through time during angiosperm evolution. The proposal is made that the genetics of the angiosperms pressured the evolution of the group toward reproductive systems that favored outcrossing. This resulted in the strongest selection in the angiosperms being directed toward the flower, fruits, and seeds. That is why these organs often provide the best systematic characters for the group.

New trends in natural language processing: statistical natural language processing.

The field of natural language processing (NLP) has seen a dramatic shift in both research direction and methodology in the past several years. In the past, most work in computational linguistics tended to focus on purely symbolic methods. Recently, more and more work is shifting toward hybrid methods that combine new empirical corpus-based methods, including the use of probabilistic and information-theoretic techniques, with traditional symbolic methods. This work is made possible by the recent availability of linguistic databases that add rich linguistic annotation to corpora of natural language text. Already, these methods have led to a dramatic improvement in the performance of a variety of NLP systems with similar improvement likely in the coming years. This paper focuses on these trends, surveying in particular three areas of recent progress: part-of-speech tagging, stochastic parsing, and lexical semantics.

Time Trends in Self-Rated Health and Disability in Older Spanish People: Differences by Gender and Age

Abstract Background: To analyse time trends in self-rated health in older people by gender and age and examine disability in the time trends of self-rated health. Methods: The data used come from the Spanish National Health Surveys conducted in 2001, 2003, 2006 and 2011- 12. Samples of adults aged 16 yr and older were selected. Multivariate logistic regression was used to assess the association between age, gender, socio-economic status, marital status, disability and self-rated health across period study. Results: Women exhibited lower (higher) prevalence of good self-rated health (disability) compared to men. The multivariate analysis for time trends found that good self-rated health increased from 2001 to 2012. Overall, variables associated with a lower likelihood of good self-rated health were: being married or living with a partner, lower educational level, and disability. Conclusion: Trends of good self-rated health differ by gender according to socio-demographic factors and the prevalence of disability.

Participation and performance trends in 6-hour ultra-marathoners – a retrospective data analysis of worldwide participation from 1991-2010

Participation trends in 6-hour ultra-marathons held word-wide were investigated to gain basic demographic data on 6-hour ultra-marathoners and where these races took place. Participation trends and the association between nationality and race performance were investigated in all 6-hour races held worldwide between 1991 and 2010. Participation increased linearly in both women and men across years. The annual number of finishes was significantly higher in men than in women (P=0.013). The male-to-female ratio remained stable at ~4 since 1991. Runners in age group 45-49 years showed the largest increase in participation for both men (800 participants in 18 years) and women (208 participants in 16 years). Europe attracted most of the runners from other continents (166 runners), more than all other continents combined (55 runners). European runners also showed the best top ten performances (73±3 km for women and 77±11 km for men), while African (with 65±9 km for men) and South American (54±4 km for women and 65±2 km for men) runners showed the weakest. To summarize, participation in 6-hour ultra-marathons increased across years. Most of the development took place in Europe and in athletes in the age group 45-49 years. Europe also attracted the most diverse field of athletes with runners from all other continents. European runners accounted for the most runners and achieved the best top ten performances.

Trends in socioeconomic inequalities in amenable mortality in urban areas of Spanish cities, 1996-2007

Background: While research continues into indicators such as preventable and amenable mortality in order to evaluate quality, access, and equity in the healthcare, it is also necessary to continue identifying the areas of greatest risk owing to these causes of death in urban areas of large cities, where a large part of the population is concentrated, in order to carry out specific actions and reduce inequalities in mortality. This study describes inequalities in amenable mortality in relation to socioeconomic status in small urban areas, and analyses their evolution over the course of the periods 1996–99, 2000–2003 and 2004–2007 in three major cities in the Spanish Mediterranean coast (Alicante, Castellón, and Valencia). Methods: All deaths attributed to amenable causes were analysed among non-institutionalised residents in the three cities studied over the course of the study periods. Census tracts for the cities were grouped into 3 socioeconomic status levels, from higher to lower levels of deprivation, using 5 indicators obtained from the 2001 Spanish Population Census. For each city, the relative risks of death were estimated between socioeconomic status levels using Poisson’s Regression models, adjusted for age and study period, and distinguishing between genders. Results: Amenable mortality contributes significantly to general mortality (around 10%, higher among men), having decreased over time in the three cities studied for men and women. In the three cities studied, with a high degree of consistency, it has been seen that the risks of mortality are greater in areas of higher deprivation, and that these excesses have not significantly modified over time. Conclusions: Although amenable mortality decreases over the time period studied, the socioeconomic inequalities observed are maintained in the three cities. Areas have been identified that display excesses in amenable mortality, potentially attributable to differences in the healthcare system, associated with areas of greater deprivation. Action must be taken in these areas of greater inequality in order to reduce the health inequalities detected. The causes behind socioeconomic inequalities in amenable mortality must be studied in depth.