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Cancer remains a leading cause of death in the USA and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola, along with several other Annonaceous species, have been extensively investigated for anticancer, anti-inflammatory and antioxidant properties. Phytochemical studies have identified the acetogenins, a class of bioactive polyketide-derived constituents, from the extracts of Annonaceous species, and dozens of these compounds are present in different parts of graviola. This review summarizes current literature on the therapeutic potential and molecular mechanism of these constituents from A.muricata against cancer and many non-malignant diseases. Based on available data, there is good evidence that these long-used plants could have both chemopreventive and therapeutic potential. Appropriate attention to safety studies will be important to assess their effectiveness on various diseases caused or promoted by inflammation.

We have used 605 days of photometric data from the Kepler spacecraft to study KIC 6614501, a close binary system with an orbital period of 0.15749747(25) days (3.779939 hours), that consists of a low-mass subdwarf B (sdB) star and a white dwarf. As seen in many other similar systems, the gravitational field of the white dwarf produces an ellipsoidal deformation of the sdB which appears in the light curve as a modulation at two times the orbital frequency. The ellipsoidal deformation of the sdB implies that the system has a maximum inclination of ~40 degrees, with i \approx 20 degrees being the most likely. The orbital radial velocity of the sdB star is high enough to produce a Doppler beaming effect with an amplitude of 432 \pm 5 ppm, clearly visible in the folded light curve. The photometric amplitude that we obtain, K1 = 85.8 km/s, is ~12 per cent less than the spectroscopic RV amplitude of 97.2 \pm 2.0 km/s. The discrepancy is due to the photometric contamination from a close object at about 5 arcsec North West of KIC 6614501, which is difficult to remove. The atmospheric parameters of the sdB star, Teff = 23 700 \pm 500 K and log g = 5.70 \pm 0.10, imply that it is a rare object below the Extreme Horizontal Branch (EHB), similar to HD 188112 (Heber et al. 2003). The comparison with different evolutionary tracks suggests a mass between ~0.18 and ~0.25 Msun, too low to sustain core helium burning. If the mass was close to 0.18-0.19 Msun, the star could be already on the final He-core WD cooling track. A higher mass, up to ~0.25 Msun, would be compatible with a He-core WD progenitor undergoing a cooling phase in a H-shell flash loop. A third possibility, with a mass between ~0.32 and ~0.40 Msun, can not be excluded and would imply that the sdB is a "normal" (but with an unusually low mass) EHB star burning He...

We present a hierarchical triple star system (KIC 9140402) where a low mass eclipsing binary orbits a more massive third star. The orbital period of the binary (4.98829 Days) is determined by the eclipse times seen in photometry from NASA's Kepler spacecraft. The periodically changing tidal field, due to the eccentric orbit of the binary about the tertiary, causes a change in the orbital period of the binary. The resulting eclipse timing variations provide insight into the dynamics and architecture of this system and allow the inference of the total mass of the binary ($0.424 \pm 0.017 \text{M}_\odot$) and the orbital parameters of the binary about the central star.

DELLA proteins are nuclear-localized negative regulators of gibberellin signaling found ubiquitously throughout higher plants. Dominant dwarfing mutations of DELLA proteins have been primarily responsible for the dramatic increases in harvest index of the 'green revolution'. Maize contains two genetic loci encoding DELLA proteins, dwarf plant8 (d8) and dwarf plant 9 (d9). The d8 gene and three of its dominant dwarfing alleles have been previously characterized at the molecular level. Almost 20 years after the initial description of the mutant, this investigation represents the first molecular characterization of d9 and its gibberellin-insensitive mutant, D9-1. We have molecularly, subcellularly and phenotypically characterized the gene products of five maize DELLA alleles in transgenic Arabidopsis. In dissecting the molecular differences in D9-1, a critical residue for normal DELLA function has been uncovered, corresponding to E600 of the D9 protein. The gibberellin-insensitive D9-1 was found to produce dwarfing and, notably, earlier flowering in Arabidopsis. Conversely, overexpression of the D9-1 allele delayed flowering in transgenic maize, while overexpression of the d9 allele led to earlier flowering. These results corroborate findings that DELLA proteins are at the crux of many plant developmental pathways and suggest differing mechanisms of flowering time control by DELLAs in maize and Arabidopsis.

From 1982 to 1984, the authors conducted a population-based case-control study of lung cancer in men and women nonsmokers in New York State. In-person interviews were completed for 437 lung cancer cases (197 never smokers, 240 former smokers) and 437 matched population controls. Cases and controls were asked to report any history of physician-diagnosed nonmalignant lung disease; cases were more likely than controls to report such a history. Statistically significant associations were found for emphysema (odds ratio (OR) = 1.94, 95% confidence interval (CI) 1.10-3.43), chronic bronchitis (OR = 1.73, 95% CI 1.10-2.72), and the combined endpoint of emphysema, chronic bronchitis, or asthma (OR = 1.82, 95% CI 1.26-2.63). After adjustment for active and passive tobacco smoke exposure, emphysema, chronic bronchitis, and asthma (each condition and the combined endpoint) were significantly associated with lung cancer risk. The risk was more marked for squamous cell carcinomas and for subjects who were diagnosed at older ages, and it remained significant when surrogate interviews were excluded. These results are consistent with the hypothesis that certain prior lung conditions increase the risk of lung cancer in men and women nonsmokers.

BACKGROUND Approximately 15% of all lung cancer deaths in the United States (about 22,350 deaths annually) may not be directly attributable to active cigarette smoking. Consumption of beta carotene, which is derived almost exclusively from intake of fruits and vegetables, has been associated with a reduced risk of lung cancer in smokers. However, studies examining this association in nonsmokers, particularly nonsmoking men, are limited. PURPOSE The purpose of this study was to examine whether dietary factors including beta carotene and retinol are associated with a reduced risk for lung cancer in nonsmoking men and women. METHODS A population-based, matched case-control study of lung cancer in nonsmokers was conducted in New York State from 1982 to 1985. Dietary interviews were completed for 413 individually matched case-control pairs of subjects. To determine whether the relationship between dietary intake from specific food groups and lung cancer differed by type of interview, smoking history, sex, age, or histologic type, we examined data on the case-control pairs from each subgroup separately. The intake of beta carotene and retinol was calculated as the weighted sum of the monthly frequencies of consumption of food items containing these nutrients, where the weights correspond to the nutrient content of a typical portion of the food items. RESULTS Consumption of greens (P for trend < .01), fresh fruits (P for trend < .01), and cheese (P for trend < .05) was associated with a significant dose-dependent reduction in risk for lung cancer, whereas consumption of whole milk (P for trend < .01) was associated with a significant dose-dependent increase in risk. Use of vitamin E supplements was also protective (odds ratio = 0.55; 95% confidence interval [CI] = 0.35-0.85). Increased consumption of the following food groups was associated with a reduction in risk among females: vegetables (P for trend < .025), raw fruits and vegetables (P for trend < .005), and dairy products (P for trend < .025). In males, increased consumption of raw fruits and vegetables was associated with a reduced risk for lung cancer (P for trend < .005). Dietary beta carotene (OR = 0.70; 95% CI = 0.50-0.99), but not retinol (OR = 0.98; 95% CI = 0.82-1.17), was significantly associated with risk reduction. CONCLUSIONS This is the largest study to date of dietary factors and lung cancer in nonsmokers; results suggest that dietary beta carotene, raw fruits and vegetables, and vitamin E supplements reduce the risk of lung cancer in nonsmoking men and women.

We present software tools for overcoming the problem of combinatorics in the enumeration of simple pathways and simple cycles in a first flow-through analysis of carbon transfer in large ecosystems. Rather than search through the very large number of potential routes in a reasonably sized ecosystem for the relatively small number of actual routes, our main algorithm performs an efficient rule-based construction of the actual routes. The enumeration of the unique pathways becomes tractable in terms of CPU time, which increases linearly with ecosystem size and connectedness. Networks of up to 80 entities can be evaluated using our software.

Enacted in 1906, the Antiquities Act is one of the most important pieces of conservation legislation in American history and has had a far-reaching influence on the preservation of our nation's cultural and natural heritage. Thanks to the foresight of thirteen presidents, parks as diverse as Acadia, Grand Canyon, and Olympic National Park, along with historic and archaeological sites such as Thomas Edison's Laboratory and the Gila Cliff Dwellings, have been preserved for posterity. A century after its passage, this book presents a definitive assessment of the Antiquities Act and its legacy, addressing the importance and breadth of the act, s well as the controversy it has engendered. Authored by professionals intimately involved with safeguarding the nation's archaeological, historic, and natural heritage, it describes the applications of the act and assesses its place in our country's future. With a scope as far-reaching as the resources the act embraces, this book offers an unparalleled opportunity for today's stewards to reflect on the act's historic accomplishments, to remind fellow professionals and the general public of its continuing importance, and to look ahead to its continuing implementation in the twenty-first century. The Antiquities Act invites all who love America's natural and cultural treasures not only to learn about the act's rich legacy but also to envision its next hundred years.

We investigated the relationship between hypertension and breast cancer using data from a large case-control study of women younger than 55 years. Among nulliparous women, there was little evidence of an association between hypertension and breast cancer. Among parous women, hypertension reduced the risk of breast cancer if it had been diagnosed at any time in their lives before the end of the most recent pregnancy (odds ratio = 0.73; 95% confidence interval = 0.59-0.92). Several earlier studies indicate that there is an association between hypertension during pregnancy and elevated levels of maternal serum alpha-fetoprotein. Thus, our results are consistent with the hypothesis that maternal exposure to alpha-fetoprotein during pregnancy protects women against the subsequent occurrence of breast cancer.

This report compares the history of oral contraceptive (OC) use for 715 New York state women who gave birth to malformed infants with the history for a group of 715 matched controls who gave birth to normal children. The case mothers were found to have used the OC after last menstrual period (LMP), or just before conception, slightly more often than the controls. Confidence intervals for the relative risk estimates were wide, and were significantly higher than 1.0 only among the group of women whose children had one or more major structural or anatomical malformations. Cytogenetic abnormalities and hypospadias were not associated with OC use around or after the time of conception. For women who had children with major anatomical or structural malformations, the association with OCs was stronger among the older age group. The authors found no evidence of an increased risk among women who had conveived their child after one or more pill-free menstrual cycles. Several reported studies, including this one, show a predominance of males among malformed offspring whose mothers used OCs during pregnancy. These findings indicate that the association between birth defects and OC use around the time of conception is not large, but the association is not easily reconciled with a non-causal explanation.This report compares the history of (OC) oral contraceptive use for 715 New York State women who gave birth to malformed infants with the history for a group of 715 matched controls who gave birth to normal children. The case mothers were found to have used OCs after their last menstrual period or just before conceptions slightly more often than the controls. Confidence intervals for the relative risk estimates were wide, and were significantly higher than 1.0 only among the group of women whose children had 1 or more major structural or anatomical malformations. Cytogenetic abnormalities and hypospadias were not associated with OC use around or after the time of conception. For women who had children with major anatomical or structural malformations, the association with OCs was stronger among the older age group. The authors found no evidence of an increased risk among women who had conceived their child after 1 or more pill-free menstrual cycles. Several reported studies, including this 1, show a predominance of males among malformed offspring whose mothers used OCs during pregnancy. These findings indicate that the association between birth defects and OC use around the time of conception is not large, but the association is not easily reconciled with a noncausal explanation.

Population projections and age-stratified cancer rates were used to forecast the trends for cancer occurrence for the United States during the coming decades: A progressive increase in the number of new cases is already predetermined by the high birth rate that occurred during the middle part of the century, and it will lead to nearly a doubling in the number of cases in about 4 decades. The demographic circumstances that determine the per capita costs of cancer are likely to worsen, because expected population trends will produce a deteriorating per capita economic base. Furthermore, the high costs of emerging treatment technologies are likely to magnify the deterioration ever further. Development of methods for cancer trend forecasting can provide a sound and accurate foundation for planning a comprehensive national strategy for optimal partitioning of research resources between the need for development of new treatments and the need for new research directed toward primary preventive measures.