The Accumulation of Tissue Cholesterol and Its Relationship to Bile Acid and Sterol Turnover

Normal and hypophysectomized rats were divided into equal homogeneous groups to determine the effect of cholestyramine, corn oil and cholesterol on the excretion of fecal bile acids and sterols. Bile acid turnover rates, pool sizes, and spectrums were studied and compared

Technology requirements of exploration beyond Neptune by solar sail propulsion

This paper provides a set of requirements for the technology development of a solar sail propelled Interstellar Heliopause Probe mission. The mission is placed in the context of other outer solar systems missions, ranging from a Kuiper Belt mission through to an Oort cloud mission. Mission requirements are defined and a detailed parametric trajectory analysis and launch date scan performed. Through analysis of the complete mission trade space a set of critical technology development requirements are identified which include an advanced lightweight composite High-Gain Antenna, a high-efficiency Ka-band travelling-wave tube amplifier and a radioisotope thermoelectric generator with power density of approximately 12 W/kg. It is also shown that the Interstellar Heliopause Probe mission necessitates the use of a spinning sail, limiting the direct application of current hardware development activities. A Kuiper Belt mission is then considered as a pre-curser to the Interstellar Heliopause Probe, while it is also shown through study of an Oort cloud mission that the Interstellar Heliopause Probe mission is the likely end-goal of any future solar sail technology development program. As such, the technology requirements identified to enable the Interstellar Heliopause Probe must be enabled through all prior missions, with each mission acting as an enabling facilitator towards the next

Extension of Earth-Moon libration point orbits with solar sail propulsion

This paper presents families of libration point orbits in the Earth-Moon system that originate from complementing the classical circular restricted three-body problem with a solar sail. Through the use of a differential correction scheme in combination with a continuation on the solar sail induced acceleration, families of Lyapunov, halo, vertical Lyapunov, Earth-centred, and distant retrograde orbits are created. As the solar sail circular restricted three-body problem is non-autonomous, a constraint defined within the differential correction scheme ensures that all orbits are periodic with the Sun’s motion around the Earth-Moon system. The continuation method then starts from a classical libration point orbit with a suitable period and increases the solar sail acceleration magnitude to obtain families of orbits that are parametrised by this acceleration. Furthermore, different solar sail steering laws are considered (both in-plane and out-of-plane, and either fixed in the synodic frame or fixed with respect to the direction of sunlight), adding to the wealth of families of solar sail enabled libration point orbits presented. Finally, the linear stability properties of the generated orbits are investigated to assess the need for active orbital control. It is shown that the solar sail induced acceleration can have a positive effect on the stability of some orbit families, especially those at the L2 point, but that it most often (further) destabilises the orbit. Active control will therefore be needed to ensure long-term survivability of these orbits

Prediction of specificity-determining residues for small-molecule kinase inhibitors

<p>Abstract</p> <p>Background</p> <p>Designing small-molecule kinase inhibitors with desirable selectivity profiles is a major challenge in drug discovery. A high-throughput screen for inhibitors of a given kinase will typically yield many compounds that inhibit more than one kinase. A series of chemical modifications are usually required before a compound exhibits an acceptable selectivity profile. Rationalizing the selectivity profile for a small-molecule inhibitor in terms of the specificity-determining kinase residues for that molecule can be an important step toward the goal of developing selective kinase inhibitors.</p> <p>Results</p> <p>Here we describe S-Filter, a method that combines sequence and structural information to predict specificity-determining residues for a small molecule and its kinase selectivity profile. Analysis was performed on seven selective kinase inhibitors where a structural basis for selectivity is known. S-Filter correctly predicts specificity determinants that were described by independent groups. S-Filter also predicts a number of novel specificity determinants that can often be justified by further structural comparison.</p> <p>Conclusion</p> <p>S-Filter is a valuable tool for analyzing kinase selectivity profiles. The method identifies potential specificity determinants that are not readily apparent, and provokes further investigation at the structural level.</p

HNO Binding in a Heme Protein: Structures, Spectroscopic Properties, and Stabilities

HNO can interact with numerous heme proteins, but atomic level structures are largely unknown. In this work, various structural models for the first stable HNO heme protein complex, MbHNO (Mb, myoglobin), were examined by quantum chemical calculations. This investigation led to the discovery of two novel structural models that can excellently reproduce numerous experimental spectroscopic properties. They are also the first atomic level structures that can account for the experimentally observed high stabilities. These two models involve two distal His conformations as reported previously for MbCNR and MbNO. However, a unique dual hydrogen bonding feature of the HNO binding was not reported before in heme protein complexes with other small molecules such as CO, NO, and O2. These results shall facilitate investigations of HNO bindings in other heme proteins