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71.
Peter T. Meinke Wesley L. Shoop Bruce F. Michael Timothy A. Blizzard Gerard R. Dawson Michael H. Fisher Helmut Mrozik 《Bioorganic & medicinal chemistry letters》1998,8(24):224-3646
A series of gem-difluoro-avermectin derivatives was synthesized from the corresponding ketones at positions 4″, 4′, 13, and 23 using diethylaminosulfur trifluoride (DAST). These fluorinated avermectins exhibit potent antiparasitic activity in a new Haemonchus contortus larval assay and are equipotent to ivermectin. In addition, 23-gem-difluoro-ivermectin displays useful anticonvulsant activity in mouse models. 相似文献
72.
Background
Quantifying the amount of standing genetic variation in fitness represents an empirical challenge. Unfortunately, the shortage of detailed studies of the genetic architecture of fitness has hampered progress in several domains of evolutionary biology. One such area is the study of sexual selection. In particular, the evolution of adaptive female choice by indirect genetic benefits relies on the presence of genetic variation for fitness. Female choice by genetic benefits fall broadly into good genes (additive) models and compatibility (non-additive) models where the strength of selection is dictated by the genetic architecture of fitness. To characterize the genetic architecture of fitness, we employed a quantitative genetic design (the diallel cross) in a population of the seed beetle Callosobruchus maculatus, which is known to exhibit post-copulatory female choice. From reciprocal crosses of inbred lines, we assayed egg production, egg-to-adult survival, and lifetime offspring production of the outbred F1 daughters (F1 productivity). 相似文献73.
74.
75.
Ratcliffe RW Wilkening RR Wildonger KJ Waddell ST Santorelli GM Parker DL Morgan JD Blizzard TA Hammond ML Heck JV Huber J Kohler J Dorso KL St Rose E Sundelof JG May WJ Hammond GG 《Bioorganic & medicinal chemistry letters》1999,9(5):679-684
A series of 1beta-methyl-2-(naphthosultamyl)methyl-carbapenems bearing dicationic groups on the naphthosultamyl moiety was prepared and evaluated for activity against resistant gram-positive bacteria. Based on a combination of excellent in vitro antibacterial activity, acceptable mouse acute toxicity, and a desirable fragmentation pattern on beta-lactam ring opening, the analog 2g (L-786,392) was selected for extended evaluation. 相似文献
76.
I A F van der Mei A-L Ponsonby T Dwyer L Blizzard R Simmons B V Taylor H Butzkueven T Kilpatrick 《BMJ (Clinical research ed.)》2003,327(7410):316
Objective To examine whether past high sun exposure is associated
with a reduced risk of multiple sclerosis.Design Population based case-control study.Setting Tasmania, latitudes 41-3°S.Participants 136 cases with multiple sclerosis and 272 controls
randomly drawn from the community and matched on sex and year of birth.Main outcome measure Multiple sclerosis defined by both clinical and
magnetic resonance imaging criteria.Results Higher sun exposure when aged 6-15 years (average 2-3 hours
or more a day in summer during weekends and holidays) was associated with a
decreased risk of multiple sclerosis (adjusted odds ratio 0.31, 95% confidence
interval 0.16 to 0.59). Higher exposure in winter seemed more important than
higher exposure in summer. Greater actinic damage was also independently
associated with a decreased risk of multiple sclerosis (0.32, 0.11 to 0.88 for
grades 4-6 disease). A dose-response relation was observed between multiple
sclerosis and decreasing sun exposure when aged 6-15 years and with actinic
damage.Conclusion Higher sun exposure during childhood and early
adolescence is associated with a reduced risk of multiple sclerosis.
Insufficient ultraviolet radiation may therefore influence the development of
multiple sclerosis. 相似文献
77.
Changhai?Ding Flavia?Cicuttini Leigh?Blizzard Graeme?JonesEmail author 《Arthritis research & therapy》2005,8(1):R8
To describe the differences in knee structure and non-knee structural factors between offspring having at least one parent
with a total knee replacement for severe primary knee osteoarthritis and age- and sex-matched controls with no family history
of knee osteoarthritis, a population-based longitudinal study of 163 matched pairs (mean age 45 years, range 26 to 61) was
performed at baseline and about 2 years later. Knee cartilage defect score (0 to 4), cartilage volume and bone size were determined
with T1-weighted fat saturation magnetic resonance imaging. Body mass index (BMI), lower-limb muscle strength, knee pain,
physical work capacity at 170 beats/minute (PWC170) and radiographic osteoarthritis were measured by standard protocols. In
comparison with controls, offspring had higher annual knee cartilage loss (-3.1% versus -2.0% at medial tibial site, -1.9%
versus -1.1% at lateral tibial site and -4.7% versus -3.7% at patellar site, all P < 0.05), a greater increase in medial cartilage defect score (+0.15 versus -0.01, P < 0.05) and a greater decline in PWC170 (-0.7 watts/kg versus -0.4 watts/kg, P < 0.01). There were no significant differences in change in BMI, lower-limb muscle strength, knee pain or tibial bone area
between these two groups; however, the differences in knee cartilage loss and cartilage defect change decreased in magnitude
and became non-significant after adjustment for baseline cartilage volume, tibial bone area, BMI and knee pain. This longitudinal
study suggests that knee cartilage loss, change in cartilage defects and decrease in physical fitness all have roles in the
development of knee osteoarthritis, which is most probably polygenic but may reflect a shared environment. Importantly, the
cartilage changes are largely dependent on baseline differences in cartilage volume, tibial bone area, BMI and knee pain,
suggesting that these factors might have a role in their initiation. 相似文献
78.
Blizzard TA DiNinno F Chen HY Kim S Wu JY Chan W Birzin ET Yang YT Pai LY Hayes EC DaSilva CA Rohrer SP Schaeffer JM Hammond ML 《Bioorganic & medicinal chemistry letters》2005,15(17):3912-3916
An optimized side chain for dihydrobenzoxathiin SERAMs was discovered and attached to four dihydrobenzoxathiin platforms. The novel SERAMs show exceptional estrogen antagonist activity in uterine tissue and an MCF-7 breast cancer cell assay. 相似文献
79.
80.
Blizzard TA DiNinno F Morgan JD Chen HY Wu JY Gude C Kim S Chan W Birzin ET Tien Yang Y Pai LY Zhang Z Hayes EC DaSilva CA Tang W Rohrer SP Schaeffer JM Hammond ML 《Bioorganic & medicinal chemistry letters》2004,14(15):3861-3864
A series of benzoxathiin SERAMs with bicyclic amine side chains was prepared. Minor modifications in the side chain resulted in significant effects on biological activity, especially in uterine tissue. 相似文献