Self-consistent calculations of the electric giant dipole resonances in light and heavy nuclei.

While bulk properties of stable nuclei are successfully reproduced by mean-field theories employing effective interactions, the dependence of the centroid energy of the electric giant dipole resonance on the nucleon number A is not. This problem is cured by considering many-particle correlations beyond mean-field theory, which we do within the quasiparticle time blocking approximation. The electric giant dipole resonances in 16O, 40Ca, and 208Pb are calculated using two new Skyrme interactions.

Survivin modulates genes with divergent molecular functions and regulates proliferation of hematopoietic stem cells through Evi-1.

The inhibitor of apoptosis protein Survivin regulates hematopoiesis, although its mechanisms of regulation of hematopoietic stem cells (HSCs) remain largely unknown. While investigating conditional Survivin deletion in mice, we found that Survivin was highly expressed in phenotypically defined HSCs, and Survivin deletion in mice resulted in significantly reduced total marrow HSCs and hematopoietic progenitor cells. Transcriptional analysis of Survivin(-/-) HSCs revealed altered expression of multiple genes not previously linked to Survivin activity. In particular, Survivin deletion significantly reduced expression of the Evi-1 transcription factor indispensable for HSC function, and the downstream Evi-1 target genes Gata2, Pbx1 and Sall2. The loss of HSCs following Survivin deletion and impaired long-term HSC repopulating function could be partially rescued by ectopic Evi-1 expression in Survivin -/- HSCs. These data demonstrate that Survivin partially regulates HSC function by modulating the Evi-1 transcription factor and its downstream targets and identify new genetic pathways in HSCs regulated by Survivin.

Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets.

Both anthropologists and nutritionists have long recognized that the diets of modern-day hunter-gatherers may represent a reference standard for modern human nutrition and a model for defense against certain diseases of affluence. Because the hunter-gatherer way of life is now probably extinct in its purely un-Westernized form, nutritionists and anthropologists must rely on indirect procedures to reconstruct the traditional diet of preagricultural humans. In this analysis, we incorporate the most recent ethnographic compilation of plant-to-animal economic subsistence patterns of hunter-gatherers to estimate likely dietary macronutrient intakes (% of energy) for environmentally diverse hunter-gatherer populations. Furthermore, we show how differences in the percentage of body fat in prey animals would alter protein intakes in hunter-gatherers and how a maximal protein ceiling influences the selection of other macronutrients. Our analysis showed that whenever and wherever it was ecologically possible, hunter-gatherers consumed high amounts (45-65% of energy) of animal food. Most (73%) of the worldwide hunter-gatherer societies derived >50% (> or =56-65% of energy) of their subsistence from animal foods, whereas only 14% of these societies derived >50% (> or =56-65% of energy) of their subsistence from gathered plant foods. This high reliance on animal-based foods coupled with the relatively low carbohydrate content of wild plant foods produces universally characteristic macronutrient consumption ratios in which protein is elevated (19-35% of energy) at the expense of carbohydrates (22-40% of energy).

Clearance of a novel recombinant tissue plasminogen activator in rabbits.

The pharmacokinetic properties of hPA(B), characterized by the insertion of a urokinase kringle coding region before the double kringle of tPA plus the complete tPA coding region, were investigated and compared to those of melanoma tPA (mtPA). Mean peak plasma concentrations at the end of infusion were 4.7 micrograms/ml for hPA(B) and 4.6 micrograms/ml for mtPA. The pharmacokinetics of both hPA(B) and mtPA showed a biexponential disappearance from plasma which is consistent with a two-compartment model of t 1/2 (lambda 1) = 2 minutes, t 1/2 (lambda 2) = 58 minutes for hPA(B), and t 1/2 (lambda 1) = 2.2 minutes, t 1/2 (lambda 2) = 61 minutes for mtPA. However, this very fast decaying lambda 1 phase of mtPA lasted five times longer than that of hPA(B) which resulted in very low concentrations of mtPA. Thus, hPA(B) exhibited larger AUC, slower clearance rate, and smaller volume of distribution (P less than 0.01) than those of mtPA. The fibrinolytic activity of hPA(B) in rabbit plasma as determined by zymography lasted up to 120 minutes after the end of infusion as compared to that of 2 minutes for mtPA. This indicates that mtPA, despite its t 1/2 (lambda 2) being similar to that of hPA(B), is no longer at physiologically meaningful concentrations at the start of the lambda 2 phase.

Synthesis and biological evaluation of a 4-fluoromethyl monobactam analog.

The synthesis and in vitro antibacterial activity of (+/-)(cis)-3-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]- 4-fluoromethyl-2-oxo-1-azetidinesulfonic acid, potassium salt are presented.

Efficacy of lamotrigine in institutionalized, developmentally disabled patients with epilepsy: a retrospective evaluation.

The paper evaluates the efficacy of the newer anticonvulsant lamotrigine in a developmentally disabled patient population. A retrospective evaluation was done at two institutional centres to assess adjunctive lamotrigine (Lamictal) efficacy in a developmentally disabled population. Mean seizure frequency was compared between a 2-month pre-lamotrigine baseline period and a 2-month treatment period. A 3-month lamotrigine titration phase occurred between baseline and treatment periods. Seizure frequency data was obtained from standardized, daily seizure records. Adverse effect data was obtained from medical and nursing notes. An intent to treat analysis was performed. Data were analysed using Student's t-test for paired data. We evaluated 44 centre residents (25 male, 19 female, average age 33 +/- 11 years). Mean lamotrigine dose was 272 +/- 133 mg per day. A significant reduction in seizure frequency was noted. Seizure frequency (all seizures) was 10.1 +/- 11.2 during the baseline period vs. 5.8 +/- 7.9 seizures per month during the treatment period (P = 0.002). Thirty-two percent of patients (n = 14) had greater than a 75% reduction in seizure frequency. Twenty-three percent of patients (n = 10) had a 50-74% seizure reduction. Twenty-five percent of patients (n = 11) had less than a 50% reduction in seizures, while 20% (n = 9) had an increase in seizures. A significant reduction of 48% in generalized seizures (9.5 +/- 11.6 vs. 4.9 +/- 6.5 seizures per month, P = 0.013) was noted. Reductions in partial seizure frequency of 48% (7.9 +/- 10 vs. 4 +/- 6.6 seizures per month, P = 0.16) as well as in mixed-type seizures (19.9 +/- 9.3 was vs. 15 +/- 12.1 seizures per month, P = 0.11) were also seen; however, these changes did not reach significance. Overall, lamotrigine was well tolerated by the subject population. Adjunctive treatment with lamotrigine appears to be an efficacious and well-tolerated treatment for seizures in a significant percentage of developmentally disabled patients with epilepsy.

Coming to terms: toward a North-South bargain for the environment.

PIP: To attack the major environmental problems, global warming, natural resource losses, and loss of biological diversity, an understanding between the industrialized and developing countries must occur. Weather patterns and sea levels are being affected by global warming which is caused by the use of fossil fuels and deforestation. The industrialized countries must cut back on the use of fossil fuels, and developing countries need to slow the process of deforestation. The loss of genetic resources and the extinction of species is happening rapidly, and most of it is in the tropical forests of developing countries. The developing countries are more dependent on their natural resources, forests, minerals, soils, and fisheries than industrialized countries. They are being depleted more rapidly with the population growth, social inequalities, and poor policies. Industrial countries are partly to blame also since they make investment and development decisions without concerns for the environment. The 4 major actions that can be initiated by industrialized countries are as follows. The initiation of national and international movements to reduce gas emissions that cause the greenhouse effect. The increased distribution of new technology and financing for population programs, sustainable development and environmental protection. The reduction of the external dept of developing countries, and the creation of programs to give technical assistance, scientific and other training for environmental problems of developing countries. Financial assistance can be linked to population programs and to environmental issues of the developing countries. Carbon dioxide taxes could be used to finance forest management and ecological zoning. The exchange of forest conservation for debt relief is a possible solution. Any dept restructuring plan should include strong environmental conservation provisions and policy reform requirements.^ieng

Protein selection and avoidance strategies of contemporary and ancestral foragers: unresolved issues.

During seasonal or inter-annual periods of food shortage and restricted total calorie intake, ethnographically and ethnohistorically documented human foragers, when possible, under-utilize foods that are high in protein, such as lean meat, in favour of foods with higher lipid or carbohydrate content. Nutritional studies suggest that one reason for this behaviour stems from the fact that pregnant women, particularly at times when their total calorie intake is marginal, may be constrained in the amount of energy they can safely derive from protein sources to levels below about 25% of total calories. Protein intakes above this threshold may affect pregnancy outcome through decreased mass at birth and increased perinatal morbidity and mortality. This paper briefly outlines the evidence for the existence of an upper safe limit to total protein intake in pregnancy, and then discusses several facets of the issue that remain poorly understood. The paper ends by raising two basic questions directed especially toward specialists in primate and human nutrition: is this protein threshold real and demographically significant in modern human foraging populations? If so, does an analogous threshold affect pregnant female chimpanzees? If the answer to both of these questions is yes, we can then begin to explore systematically the consequences such a threshold might have for the diet and behaviour of early hominids.