The α-arrestin ARRDC3 mediates ALIX ubiquitination and G protein-coupled receptor lysosomal sorting.

The sorting of G protein-coupled receptors (GPCRs) to lysosomes is critical for proper signaling and cellular responses. We previously showed that the adaptor protein ALIX regulates lysosomal degradation of protease-activated receptor-1 (PAR1), a GPCR for thrombin, independent of ubiquitin-binding ESCRTs and receptor ubiquitination. However, the mechanisms that regulate ALIX function during PAR1 lysosomal sorting are not known. Here we show that the mammalian α-arrestin arrestin domain-containing protein-3 (ARRDC3) regulates ALIX function in GPCR sorting via ubiquitination. ARRDC3 colocalizes with ALIX and is required for PAR1 sorting at late endosomes and degradation. Depletion of ARRDC3 by small interfering RNA disrupts ALIX interaction with activated PAR1 and the CHMP4B ESCRT-III subunit, suggesting that ARRDC3 regulates ALIX activity. We found that ARRDC3 is required for ALIX ubiquitination induced by activation of PAR1. A screen of nine mammalian NEDD4-family E3 ubiquitin ligases revealed a critical role for WWP2. WWP2 interacts with ARRDC3 and not ALIX. Depletion of WWP2 inhibited ALIX ubiquitination and blocked ALIX interaction with activated PAR1 and CHMP4B. These findings demonstrate a new role for the α-arrestin ARRDC3 and the E3 ubiquitin ligase WWP2 in regulation of ALIX ubiquitination and lysosomal sorting of GPCRs

A proposal for highly tunable optical parametric oscillation in silicon micro-resonators

We propose a novel scheme for continuous-wave pumped optical parametric oscillation (OPO) inside silicon micro-resonators. The proposed scheme not only requires a relative low lasing threshold, but also exhibits extremely broad tunability extending from the telecom band to mid infrared

Personality traits are directly associated with anti-black prejudice in the United States

Modern psychological theories postulate that individual differences in prejudice are determined by social and ideological attitudes instead of personality. For example, the dual-process motivational (DPM) model argues that personality does not directly associate with prejudice when controlling for the attitudinal variables that capture the authoritarian-conservatism motivation and the dominance motivation. Previous studies testing the DPM model largely relied on convenience samples and/or European samples, and have produced inconsistent results. Here we examined the extent to which anti-black prejudice was associated with the Big Five personality traits and social and ideological attitudes (authoritarianism, social dominance orientation, political party affiliation) in two large probability samples of the general population (N₁ = 3,132; N₂ = 2,483) from the American National Election Studies (ANES). We performed structural equation modeling (SEM) to test the causal assumptions between the latent variables and used survey weights to generate estimates that were representative of the population. Different from prior theories, across both datasets we found that two personality traits, agreeableness and conscientiousness, were directly associated with anti-black prejudice when controlling for authoritarianism, social dominance orientation, and political party affiliation. We also found that a substantial part of the associations between personality traits and anti-black prejudice were mediated through those social and ideological attitudes, which might serve as candidates for prejudice-reduction interventions in the real world

Structures of fibrils formed by α-synuclein hereditary disease mutant H50Q reveal new polymorphs.

Deposits of amyloid fibrils of α-synuclein are the histological hallmarks of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, with hereditary mutations in α-synuclein linked to the first two of these conditions. Seeing the changes to the structures of amyloid fibrils bearing these mutations may help to understand these diseases. To this end, we determined the cryo-EM structures of α-synuclein fibrils containing the H50Q hereditary mutation. We find that the H50Q mutation results in two previously unobserved polymorphs of α-synuclein: narrow and wide fibrils, formed from either one or two protofilaments, respectively. These structures recapitulate conserved features of the wild-type fold but reveal new structural elements, including a previously unobserved hydrogen-bond network and surprising new protofilament arrangements. The structures of the H50Q polymorphs help to rationalize the faster aggregation kinetics, higher seeding capacity in biosensor cells and greater cytotoxicity that we observe for H50Q compared to wild-type α-synuclein

An Efficient Targeting Strategy for Multiobject Spectrograph Surveys: the Sloan Digital Sky Survey "Tiling" Algorithm

Large surveys using multiobject spectrographs require automated methods for deciding how to efficiently point observations and how to assign targets to each pointing. The Sloan Digital Sky Survey (SDSS) will observe around 10 6 spectra from targets distributed over an area of about 10,000 deg2, using a multiobject fiber spectrograph that can simultaneously observe 640 objects in a circular field of view (referred to as a "tile") 1°.49 in radius. No two fibers can be placed closer than 55Prime; during the same observation; multiple targets closer than this distance are said to "collide." We present here a method of allocating fibers to desired targets given a set of tile centers that includes the effects of collisions and that is nearly optimally efficient and uniform. Because of large-scale structure in the galaxy distribution (which form the bulk of the SDSS targets), a naive covering of the sky with equally spaced tiles does not yield uniform sampling. Thus, we present a heuristic for perturbing the centers of the tiles from the equally spaced distribution that provides more uniform completeness. For the SDSS sample, we can attain a sampling rate of greater than 92% for all targets, and greater than 99% for the set of targets that do not collide with each other, with an efficiency greater than 90% (defined as the fraction of available fibers assigned to targets). The methods used here may prove useful to those planning other large surveys

MPI Enhancements in John the Ripper

John the Ripper (JtR) is an open source software package commonly used by system administrators to enforce password policy. JtR is designed to attack (i.e., crack) passwords encrypted in a wide variety of commonly used formats. While parallel implementations of JtR exist, there are several limitations to them. This research reports on two distinct algorithms that enhance this password cracking tool using the Message Passing Interface. The first algorithm is a novel approach that uses numerous processors to crack one password by using an innovative approach to workload distribution. In this algorithm the candidate password is distributed to all participating processors and the word list is divided based on probability so that each processor has the same likelihood of cracking the password while eliminating overlapping operations. The second algorithm developed in this research involves dividing the passwords within a password file equally amongst available processors while ensuring load-balanced and fault tolerant behavior. This paper describes John the Ripper, the design of these two algorithms and preliminary results. Given the same amount of time, the original JtR can crack 29 passwords, whereas our algorithms 1 and 2 can crack an additional 35 and 45 passwords respectively

Economic Assessment of Food Safety Regulations: The New Approach to Meat and Poultry Inspection

USDA is now requiring all Federally inspected meat and poultry processing and slaughter plants to implement a new system called Hazard Analysis and Critical Control Points (HACCP) to reduce potentially harmful microbial pathogens in the food supply. This report finds that the benefits of the new regulations, which are the medical costs and productivity losses that are prevented when foodborne illnesses are averted, will likely exceed the costs, which include spending by firms on sanitation, temperature control, planning and training, and testing. Other, nonregulatory approaches can also improve food safety, such as providing market incentives for pathogen reduction, irradiation, and education and labeling to promote safe food handling and thorough cooking.food safety, foodborne illness, microbial pathogens, meat and poultry inspection, HACCP, cost of illness, consumer education, irradiation, Food Consumption/Nutrition/Food Safety, Livestock Production/Industries,