Longevity may depend on a balance between tumor suppression and tissue renewal mechanisms Campisi, J., 2003. Cancer and ageing: rival demons? Nat. Rev. Cancer 3 (5), 339–349. Mice with constitutively ...activated p53 are almost cancer free but their life span is reduced and accompanied by early tissue atrophy Tyner et al., 2002. p53 mutant mice that display early ageing-associated phenotypes. Nature 415 (6867), 45–53. Replacement of arginine (Arg) by proline (Pro) at position 72 of human p53 decreases its apoptotic potential Dumont et al., 2003. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat. Genet. 33 (3), 357–365 providing a tool to test for a similar trade-off in humans. Using a formal meta-analysis of the published literature we show that carriers of the TP53 codon 72 Pro/Pro genotype have an increased cancer risk compared to Arg/Arg carriers (p<0.05). Next, in a prospective study of 1226 people aged 85 years and over we show that carriers of the Pro/Pro genotype have a 41% increased survival (p=0.032) despite a 2.54 fold increased (p=0.007) proportional mortality from cancer. It is suggested that human p53 protect against cancer but at a cost of longevity.
Analogical Modeling (AM) is an exemplar-based general theory of description that uses both neighbors and non-neighbors (under certain well-defined conditions of homogeneity) to predict language ...behavior. This book provides a basic introduction to AM, compares the theory with nearest-neighbor approaches, and discusses the most recent advances in the theory, including psycholinguistic evidence, applications to specific languages, the problem of categorization, and how AM relates to alternative approaches of language description (such as instance families, neural nets, connectionism, and optimality theory). The book closes with a thorough examination of the problem of the exponential explosion, an inherent difficulty in AM (and in fact all theories of language description). Quantum computing (based on quantum mechanics with its inherent simultaneity and reversibility) provides a precise and natural solution to the exponential explosion in AM. Finally, an extensive appendix provides three tutorials for running the AM computer program (available online).
The development of vegetative and generative buds on thin-layer explants of tobacco (Nicotiana tabacum L. cv. Samsun) has been studied at the level of translatable mRNA to detect changes in the mRNA ...population during bud initiation and differentiation, and several quantitative differences were found. By differential screening of a cDNA library obtained from flower-bud-regenerating explants we have isolated a group of six cDNA clones representing genes that are preferentially expressed during in-vitro flower bud formation. Nucleotide sequence analysis of one of these cDNAs, pAP8, showed that the most likely open reading frame has some typical characteristics of and homology with, extensin-like genes. Northern blot analysis and in-situ hybridization suggest a specific role for these extensin-like genes in flower bud initiation on tobacco pedicel explants.
The effects of continuously infused dopamine and norepinephrine on hemodynamics, oxygen metabolism, and right ventricular (RV) performance were studied by crossover design in ten patients with septic ...shock who needed treatment with vasoactive drugs after fluid replacement. Standard hemodynamic measurements were obtained and RV performance assessed before and 1 h after the start of the infusion. All but one patient had pulmonary hypertension, and in seven the RV ejection fraction (RVEF) was lower than 50 percent at baseline. Drugs were titrated to a systolic arterial blood pressure of mean 106 ± 18 mm Hg for dopamine and 116 ± 20 mm Hg for norepinephrine (NS). Dopamine infusion increased the cardiac index (CI) 16 percent (p<0.02), but heart rate and systemic and pulmonary vascular resistances were unchanged. With norepinephrine CI was unchanged, a heart rate decreased 7 percent (p<0.05), and systemic and pulmonary vascular resistance increased 35 and 26 percent, respectively (p<0.05). With both drugs, RV volumes and RVEF remained unchanged, and systemic oxygen consumption increased equally (by 19 percent for dopamine and 22 percent for norepinephrine, p<0.05); systemic oxygen delivery rose by 17 percent during dopamine infusion and was unchanged during norepinephrine infusion. Norepinephrine increased oxygen extraction vs dopamine (p<0.05). There were no differences in urinary output. Norepinephrine may improve the RV oxygen supply/demand ratio, but this potentially beneficial effect on RV ejection fraction may be offset by a concomitant increase in pulmonary vascular resistance and RV afterload. Norepinephrine may not adversely affect the peripheral circulation. In short-term treatment of volume-resuscitated, severe septic shock complicated by pulmonary hypertension and impaired RV performance, norepinephrine may be at least as effective as dopamine.
