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

Wannier-Stark ladders in one-dimensional elastic systems

The optical analogues of Bloch oscillations and their associated Wannier-Stark ladders have been recently analyzed. In this paper we propose an elastic realization of these ladders, employing for this purpose the torsional vibrations of specially designed one-dimensional elastic systems. We have measured, for the first time, the ladder wave amplitudes, which are not directly accessible either in the quantum mechanical or optical cases. The wave amplitudes are spatially localized and coincide rather well with theoretically predicted amplitudes. The rods we analyze can be used to localize different frequencies in different parts of the elastic systems and viceversa.Comment: 10 pages, 6 figures, accepted in Phys. Rev. Let

Dark Sector from Interacting Canonical and Non-Canonical Scalar Fields

In this work it is investigated general models with interactions between two canonical scalar fields and between one non-canonical (tachyon-type) and one canonical scalar field. The potentials and couplings to the gravity are selected through the Noether symmetry approach. These general models are employed to describe interactions between dark energy and dark matter, with the fields being constrained by the astronomical data. The cosmological solutions of some cases are compared with the observed evolution of the late Universe.Comment: 20 pages, 13 figures, correction of misprints in eqs. (4), (5), (43), (44

Which assessment tools address the categories of the Brief ICF Core Set for Hand Conditions?

Introduction The purpose of this study was to explore whether assessment tools address aspects that are relevant according to the Brief ICF Core Set for Hand Conditions (BICF-CS). Methods Assessment tools meant to assess functioning and/or environmental factors in adults with hand conditions were reviewed. MEDLINE and CINAHL databases, previously published reviews, the book Clinical Assessment Recommendations of the ASHT, and websites of assessment tools were used for the content comparison and linking to the 23 categories of the BICF-CS. The updated version of the linking rules was applied by two reviewers. Results Forty-six assessment tools, known within the areas of hand therapy and hand surgery, were linked to the 23 categories of the BICF-CS. Regarding Body functions and body structures, the categories that were most frequently addressed were b730 “Muscle power functions,” b280 “Sensation of pain,” b710 “Mobility of joint functions,” and s730 “Structure of upper extremity.” Regarding Activities and Participation, d440 “Fine hand use” was addressed mostly and 25 assessment tools (with a total of 146 items) were linked to this category. Regarding Environmental Factors, only one assessment tool was identified that could be linked to two categories. Fifteen points of discussion were encountered in the linking process. Conclusions Content comparison of 46 assessment tools revealed that 19 of the 23 categories of the BICF-CS were addressed. The environmental factors were hardly addressed

Galactic Bulge Microlensing Optical Depth from EROS-2

We present a new EROS-2 measurement of the microlensing optical depth toward the Galactic Bulge. Light curves of $5.6\times 10^{6}$ clump-giant stars distributed over $66 \deg^2$ of the Bulge were monitored during seven Bulge seasons. 120 events were found with apparent amplifications greater than 1.6 and Einstein radius crossing times in the range 5 {\rm d}. This is the largest existing sample of clump-giant events and the first to include northern Galactic fields. In the Galactic latitude range 1.4\degr<|b|<7.0\degr, we find $\tau/10^{-6}=(1.62 \pm 0.23)\exp[-a(|b|-3 {\rm deg})]$ with $a=(0.43 \pm0.16)\deg^{-1}$. These results are in good agreement with our previous measurement, with recent measurements of the MACHO and OGLE-II groups, and with predictions of Bulge models.Comment: accepted A&A, minor revision

Observation of periodic variable stars towards the galactic spiral arms by EROS II

We present the results of a massive variability search based on a photometric survey of a six square degree region along the Galactic plane at ($l = 305^\circ$, $b = -0.8^\circ$) and ($l = 330^\circ$, $b = -2.5^\circ$). This survey was performed in the framework of the EROS II (Exp\'erience de Recherche d'Objets Sombres) microlensing program. The variable stars were found among 1,913,576 stars that were monitored between April and June 1998 in two passbands, with an average of 60 measurements. A new period-search technique is proposed which makes use of a statistical variable that characterizes the overall regularity of the flux versus phase diagram. This method is well suited when the photometric data are unevenly distributed in time, as is our case. 1,362 objects whose luminosity varies were selected. Among them we identified 9 Cepheids, 19 RR Lyrae, 34 Miras, 176 eclipsing binaries and 266 Semi-Regular stars. Most of them are newly identified objects. The cross-identification with known catalogues has been performed. The mean distance of the RR Lyrae is estimated to be $\sim 4.9 \pm 0.3$ kpc undergoing an average absorption of $\sim 3.4 \pm 0.2$ magnitudes. This distance is in good agreement with the one of disc stars which contribute to the microlensing source star population.Our catalogue and light curves are available electronically from the CDS, Strasbourg and from our Web site http://eros.in2p3.fr.Comment: 15 pages, 11 figures, accepted in A&A (april 2002

Removing the Microlensing Blending-Parallax Degeneracy Using Source Variability

Microlensing event MACHO 97-SMC-1 is one of the rare microlensing events for which the source is a variable star, simply because most variable stars are systematically eliminated from microlensing studies. Using observational data for this event, we show that the intrinsic variability of a microlensed star is a powerful tool to constrain the nature of the lens by breaking the degeneracy between the microlens parallax and the blended light. We also present a statistical test for discriminating the location of the lens based on the \chi^2 contours of the vector \Lambda, the inverse of the projected velocity. We find that while SMC self lensing is somewhat favored over halo lensing, neither location can be ruled out with good confidence.Comment: 15 text pages + 2 tables + 7 figures. Published in the Astrophysical Journa