Advancing biological understanding and therapeutics discovery with small-molecule probes

Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the NIH launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines but also highlight the need to innovate the science of therapeutic discovery

UBVRI Light curves of 44 Type Ia supernovae

We present UBVRI photometry of 44 Type la supernovae (SNe la) observed from 1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The data set comprises 2190 observations and is the largest homogeneously observed and reduced sample of SNe la to date, nearly doubling the number of well-observed, nearby SNe la with published multicolor CCD light curves. The large sample of [U-band photometry is a unique addition, with important connections to SNe la observed at high redshift. The decline rate of SN la U-band light curves correlates well with the decline rate in other bands, as does the U - B color at maximum light. However, the U-band peak magnitudes show an increased dispersion relative to other bands even after accounting for extinction and decline rate, amounting to an additional ∼40% intrinsic scatter compared to the B band

Critical thermal maxima and minima of the platyfish Xiphophorus maculatus Günther (Poecillidae, Cyprinodontiformes): a tropical species of ornamental freshwater fish

Temperature as an environmental factor has been a frequent subject of study, since it affects either directly or indirectly all living organisms. The determination of thermal limits (critical thermal minima - CTmin and maxima - CTmax) for the tropical ornamental freshwater teleost Xiphophorus maculatus Günther, 1866 (platyfish) was performed after their acclimation to the following temperatures: 15, 20, 25, and 30ºC, for seven days. After this period, the water temperature was elevated or reduced at a rate of 0.125ºC/min until CTmax and CTmin could be determined as the temperature at which 50% of the animals had lost equilibrium. Mean values for CTmax and CTmin for the acclimation temperatures of 15, 20, 25, and 30ºC were respectively: 39.8,39.8,40.4,41.5ºC (CTmax), and 9.6, 12.8, 13.1, 16.0ºC (CTmin). CTmax and CTmin for X. maculatus were thus affected by acclimation temperature. This tropical species is more heat- than cold- tolerant and would not resist the typical low winter temperatures of southern Brazil. Platyfish can adapt to natural environments in regions of mean annual temperatures around 20-25ºC or be kept in aquaria with other ornamental species that accordingly prefer this temperature range

Data assimilation for geophysical fluids: the Diffusive Back and Forth Nudging

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