A New and Unusual Pathway for the Reaction of Neocarzinostatin Chromophore with Thiols. Revised Structure of the Protein-Directed Thiol Adduct

Neocarzinostatin (holo-NCS) is an antitumor antibiotic comprising a nonprotein chromophore component (1) and a 113- amino acid carrier protein (apo-NCS). Goldberg and coworkers first demonstrated that the reaction of the isolated chromophore (1) with thiols in the presence of double-stranded DNA leads to DNA cleavage by a free-radical mechanism. The pathway shown in Scheme 1 was later proposed to account for this activity, a proposal that is now supported by a considerable body of evidence. In 1992, Saito and co-workers showed that the reaction of holo-NCS with small thiols, such as β-mercaptoethanol (BME), takes a different course, to form a product that is formally a 1:1:1 adduct of thiol, 1, and water. Structure 2 was proposed for this adduct, along with the mechanistic pathway shown in Scheme 2. Complicating the analysis was the fact that 2 was an inseparable mixture of two components, present in equal parts

La naturaleza de la pseudociencia: algunas consideraciones sobre el estudio de fenómenos

Hace 5 años la New Yok Academy of ciences organizó una conferencia sobre el tema "La fuga de la ciencia y de la razón" (Gross et al., 1996). El objetivo de la conferencia era discutir los ataques que, según los organizadores, la ciencia ha sufrido en tiempos recientes y que colocan en riesgo la aceptación popular de la ciencia

Integrated trajectory planning and control for obstacle avoidance manoeuvre using nonlinear vehicle model-predictive algorithm

In the current literature, model-predictive (MP) algorithm is widely applied in autonomous vehicle trajectory planning and control but most of the current studies only apply the linear tyre model, which cannot accurately present the tyre non-linear characteristic. Furthermore, most of these studies separately consider the trajectory planning and trajectory control of the autonomous vehicle and few of them have integrated the trajectory planning and trajectory control together. To fill in above research gaps, this study proposes the integrated trajectory planning and trajectory control method using a non-linear vehicle MP algorithm. To fully utilise the advantages of four-wheel-independent-steering and four-wheel-independent-driving vehicle, the MP algorithm is proposed based on four-wheel dynamics model and non-linear Dugoff tyre model. This study also proposes the mathematical modelling of the static obstacle and dynamic obstacle for the obstacle avoidance manoeuvre of the autonomous vehicle. Finally, simulation results have been presented to show the effectiveness of the proposed control method

Path Planning for Autonomous Vehicle in Off-Road Scenario

The road topography information, such as bank angle and road slope, can significantly affect the trajectory tracking performance of the autonomous vehicle, so this information needs to be considered in the trajectory planning and tracking control for off-road autonomous vehicle. In this chapter, a two-level real-time dynamically integrated spatiotemporal-based trajectory planning and control method for off-road autonomous vehicle is proposed. In the upper-level trajectory planner, the most suitable time-parameterised trajectory with the minimum values of road slope and bank angle can be selected from a set of candidate trajectories. In the lower-level trajectory tracking controller, the sliding-mode control (SMC) technique is applied to control the vehicle and achieve the desired trajectory. Finally, simulation results are presented to verify the proposed integrated trajectory planning and control method and prove that the proposed integrated method has better overall tracking control and dynamics control performance than the conventional method both in the highway scenario and off-road scenario. Furthermore, the four-wheel-independent-steering (4WIS) and four-wheel-independent-driving (4WID) vehicle shows better tracking control performance than vehicle based on two-wheel model