Mechanism of Prion Propagation: Amyloid Growth Occurs by Monomer Addition

Abundant nonfibrillar oligomeric intermediates are a common feature of amyloid formation, and these oligomers, rather than the final fibers, have been suggested to be the toxic species in some amyloid diseases. Whether such oligomers are critical intermediates for fiber assembly or form in an alternate, potentially separable pathway, however, remains unclear. Here we study the polymerization of the amyloidogenic yeast prion protein Sup35. Rapid polymerization occurs in the absence of observable intermediates, and both targeted kinetic and direct single-molecule fluorescence measurements indicate that fibers grow by monomer addition. A three-step model (nucleation, monomer addition, and fiber fragmentation) accurately accounts for the distinctive kinetic features of amyloid formation, including weak concentration dependence, acceleration by agitation, and sigmoidal shape of the polymerization time course. Thus, amyloid growth can occur by monomer addition in a reaction distinct from and competitive with formation of potentially toxic oligomeric intermediates

The ‘Healthy Dads, Healthy Kids’ community effectiveness trial: study protocol of a community-based healthy lifestyle program for fathers and their children

Background: The \u27Healthy Dads, Healthy Kids\u27 program was designed to help overweight fathers lose weight and positively influence the health behaviors of their children. The aim of the current study was to evaluate the previously established program in a community setting, in a large effectiveness trial. Methods/Design: The Healthy Dads, Healthy Kids community trial consists of three stages: (i) Stage 1 - program refinement and resource development (ii) Stage 2 - community randomized controlled trial (iii) Stage 3 - community effectiveness trial. The program will be evaluated in five Local Government Areas in the Hunter Valley Region of NSW, Australia. For the community randomized controlled trial, 50 overweight/obese men (aged 18-65 years) from one Local Government Area with a child aged between 5-12 years of age will be recruited. Families will be randomized to either the program or a 6-month wait-list control group. Fathers and their children will be assessed at baseline, post-intervention (3-months) and 6-months. Inclusion criteria are: body mass index 25-40 kg/m2; no participation in other weight loss programs during the study; pass a health-screening questionnaire; and access to a computer with Internet facilities. In the community trial, the program will be evaluated using a non-randomized, prospective design in five Local Government Areas. The exclusion criteria is body mass index \u3c 25 kg/m2 or lack of doctor\u27s approval. Measures will be collected at baseline, 3-, 6- and 12-months. The program involves fathers attending seven face-to-face group sessions (three with children) over 3-months. Measures: The primary outcome is fathers\u27 weight. Secondary outcomes for both fathers and children include: waist circumference, blood pressure, resting heart rate, physical activity, sedentary behaviors and dietary intake. Father-only measures include portion size, alcohol consumption, parenting for physical activity and nutrition and parental engagement. Process evaluation will determine the fidelity, dose (delivered and received), reach, recruitment and context of the program. Discussion: As a unique approach to reducing obesity prevalence in men and improving lifestyle behaviours in children, our findings will provide important evidence relating to the translation of Healthy Dads, Healthy Kids, which will enable it to be delivered on a larger scale

A Generalized Scaling Function for AdS/CFT

We study a refined large spin limit for twist operators in the sl(2) sector of AdS/CFT. We derive a novel non-perturbative equation for the generalized two-parameter scaling function associated to this limit, and analyze it at weak coupling. It is expected to smoothly interpolate between weakly coupled gauge theory and string theory at strong coupling.Comment: 27 pages, no figures; v2: references added and typos fixe

Dynamic fragmentation of Al-W granular rings with different mesostructures

The support of this project was provided by the Office of Naval research Multidisciplinary University Research Initiative Award N00014-07-1-0740, Program Manager Dr. Clifford D. Bedford

From weak coupling to spinning strings

We identify the gauge theory dual of a spinning string of minimal energy with spins S_1, S_2 on AdS_5 and charge J on S^5. For this purpose we focus on a certain set of local operators with two different types of covariant derivatives acting on complex scalar fields. We analyse the corresponding nested Bethe equations for the ground states in the limit of large spins. The auxiliary Bethe roots form certain string configurations in the complex plane, which enable us to derive integral equations for the leading and sub-leading contribution to the anomalous dimension. The results can be expressed through the observables of the sl(2) sub-sector, i.e. the cusp anomaly f(g) and the virtual scaling function B_L(g), rendering the strong-coupling analysis straightforward. Furthermore, we also study a particular sub-class of these operators specialising to a scaling limit with finite values of the second spin at weak and strong coupling.Comment: 23 pages, 3 figures, minor changes, references adde