Proteostasis collapse is a driver of cell aging and death.

What molecular processes drive cell aging and death? Here, we model how proteostasis-i.e., the folding, chaperoning, and maintenance of protein function-collapses with age from slowed translation and cumulative oxidative damage. Irreparably damaged proteins accumulate with age, increasingly distracting the chaperones from folding the healthy proteins the cell needs. The tipping point to death occurs when replenishing good proteins no longer keeps up with depletion from misfolding, aggregation, and damage. The model agrees with experiments in the worm Caenorhabditis elegans that show the following: Life span shortens nonlinearly with increased temperature or added oxidant concentration, and life span increases in mutants having more chaperones or proteasomes. It predicts observed increases in cellular oxidative damage with age and provides a mechanism for the Gompertz-like rise in mortality observed in humans and other organisms. Overall, the model shows how the instability of proteins sets the rate at which damage accumulates with age and upends a cell's normal proteostasis balance

Role of Proteome Physical Chemistry in Cell Behavior.

We review how major cell behaviors, such as bacterial growth laws, are derived from the physical chemistry of the cell's proteins. On one hand, cell actions depend on the individual biological functionalities of their many genes and proteins. On the other hand, the common physics among proteins can be as important as the unique biology that distinguishes them. For example, bacterial growth rates depend strongly on temperature. This dependence can be explained by the folding stabilities across a cell's proteome. Such modeling explains how thermophilic and mesophilic organisms differ, and how oxidative damage of highly charged proteins can lead to unfolding and aggregation in aging cells. Cells have characteristic time scales. For example, E. coli can duplicate as fast as 2-3 times per hour. These time scales can be explained by protein dynamics (the rates of synthesis and degradation, folding, and diffusional transport). It rationalizes how bacterial growth is slowed down by added salt. In the same way that the behaviors of inanimate materials can be expressed in terms of the statistical distributions of atoms and molecules, some cell behaviors can be expressed in terms of distributions of protein properties, giving insights into the microscopic basis of growth laws in simple cells

European White Book on Real-Time Power Hardware in the Loop Testing : DERlab Report No. R- 005.0

The European White Book on Real-Time-Powerhardware-in-the-Loop testing is intended to serve as a reference document on the future of testing of electrical power equipment, with specifi c focus on the emerging hardware-in-the-loop activities and application thereof within testing facilities and procedures. It will provide an outlook of how this powerful tool can be utilised to support the development, testing and validation of specifi cally DER equipment. It aims to report on international experience gained thus far and provides case studies on developments and specifi c technical issues, such as the hardware/software interface. This white book compliments the already existing series of DERlab European white books, covering topics such as grid-inverters and grid-connected storag

The Stava mudflow of 19 July 1985 (Northern Italy): a disaster that effective regulation might have prevented

Abstract. The disaster occurring in the Eastern Italian Alps in the summer of 1985 was caused by the failure of two tailings dams located just upstream from the village of Stava in the municipality of Tesero (Trento province, Italy). The structure comprised two small storage basins for the deposition of tailings from the separation process of the Prestavel fluorite mine. On their downstream sides, the basins were contained by steep earth embankments, whereas upstream they rested directly on the natural slope. The total height from the base of the lower dam to the crest of the upper dam was over 50 m. On 19 July 1985, the front of the upper dam suddenly burst, triggering a vast mudflow (180 000 m3) that flowed down-channel through Stava, a small village of 20 buildings. The mudflow rapidly traveled over 4.2 km along the Stava Valley and passed through Tesero, before flowing into the Avisio River. The mudflow destroyed many buildings and resulted in 268 fatalities and 20 injuries. From an analysis of the data collected and field observation, several factors may be cited as having contributed to increasing instability, as the upper dam continued to be raised until the disastrous collapse of 19 July. Foremost among these factors is the mistaken assumption that the tailings deposited in the impoundments would consolidate fairly quickly. Indeed, no monitoring system was ever installed to verify the assumed consolidation. Other operational shortcomings and construction errors were contributing factors. Regulations requiring construction standards, operational monitoring, and independent periodic inspection could have prevented this disaster. Comprehensive legislation is required to effectively limit the adverse consequences of tailings dam failures by providing a regulatory environment where the safety and welfare of the local area can be balanced with the economic benefits of mining operations

Energy loss mechanism for suspended micro- and nanoresonators due to the Casimir force

A so far not considered energy loss mechanism in suspended micro- and nanoresonators due to noncontact acoustical energy loss is investigated theoretically. The mechanism consists on the conversion of the mechanical energy from the vibratory motion of the resonator into acoustic waves on large nearby structures, such as the substrate, due to the coupling between the resonator and those structures resulting from the Casimir force acting over the separation gaps. Analytical expressions for the resulting quality factor Q for cantilever and bridge micro- and nanoresonators in close proximity to an underlying substrate are derived and the relevance of the mechanism is investigated, demonstrating its importance when nanometric gaps are involved