Online Defamation: Bringing the Communications Decency Act of 1996 in Line With Sound Public Policy

According to the Communications Decency Act of 1996, a provider of an interactive computer service cannot be held liable for publishing a defamatory statement made by another party. In addition, the service provider cannot be held liable for refusing to remove the statement from its service. This article postulates that such immunity from producer and distributor liability is a suspect public policy, and argues that the statute should be amended to include a broad definition of development and a take-down and put-back provision

Novel Molecules from Environmental DNA-Derived Type II Polyketide Biosynthetic Gene Clusters

Natural products have been a significant source of new drugs over the past 25 years. In fact, the origins of nearly 70% of antibacterial, antifungal, antiparasitic and antiviral small molecule drugs are in natural products (Newman and Cragg 2007). A significant proportion of natural product drugs and leads have been isolated from microbes (Newman and Cragg 2007). However, the discovery of novel natural products from microbes faces the growing hurdle of rediscovering known metabolites. Streptomyces is a microbe that has been a particularly rich source of natural products; however, it has been predicted that the last easily accessible novel Streptomyces metabolite will be found within the next few years (Watve, Tickoo et al. 2001). Finding a new source rich in natural products would be very beneficial to the development of new drugs. One potential new source of natural products is the plethora of uncultured bacteria found in environmental soil samples. It is estimated that greater than 99% of bacteria from soil samples are recalcitrant to culturing in a laboratory setting. A culture-independent approach of extracting environmental DNA (eDNA) from soil and cloning it into a library was leveraged to take advantage of the genetic diversity of uncultured microbes. Uncultured microbes have been found to be rich in type II polyketide synthase (PKS) gene clusters (Kieser, Bibb et al. 2000). PKS gene clusters produce a structurally diverse collection of aromatic natural products. The nascent polyketide in these pathways is produced by a conserved minimal PKS, composed of an α- ketosynthase, β-ketosynthase and acyl carrier protein. In order to access the structural diversity encoded by type II PKS gene clusters from uncultured bacteria, environmental DNA (eDNA) libraries were constructed from desert soil. These libraries were found to be rich in PKS genes and cosmids containing minimal PKS genes were recovered from the eDNA library using β-ketosynthase sequences as probes. The recovered clones containing minimal PKS genes from the eDNA library were screened for the ability to confer the production of clone-specific molecules to cultured Streptomyces albus. One of the recombinant Streptomyces clones was found to produce erdacin, a 26- carbon polyketide with both a novel carbon backbone and a novel pentacyclic ring arrangement. The novel structure and pentacyclic ring arrangement of erdacin raised questions as to the biosynthetic origins of this metabolite encoded by the eDNA-derived V167 clone. A biosynthetic analysis of wild type and transposon mutant V167 cultures indicated that erdacin arises from the heterodimerization of two 13-carbon monomer subunits that are both derived from octaketide precursors. These two 13-carbon subunits arise from two different second cyclizations, but both have the same three carbons excised from their 16-carbon octaketide precursors

Shape Memory Alloys Via Halide-Activated Pack Equilibration

Fabrication of shape memory alloy (SMA) components based on NiTi is challenging due to the precision with which elemental composition and microstructure must be controlled during processing to achieve desired shape memory behavior. Herein, a method to control chemistry in an NiTi SMA via halide-activated pack equilibration (SHAPE) against a constant chemical potential reservoir is described. To demonstrate the efficacy of the SHAPE process, an initially titanium-deficient specimen (pure nickel foam) has been equilibrated against an excess of an intimately mixed two-phase pack (NiTi + Ti2Ni) in the presence of a vapor phase transport agent (iodine). The two-phase pack regulates chemical potentials in this two-component system in accordance with Gibbs\u27 phase rule. Ti-rich NiTi foams thus produced exhibit reproducible and well-defined phase transformation behaviors. The SHAPE process is advantageous for the fabrication of shape memory components of varying areal dimension, shape, and/or complexity owing to independence of the equilibrium state of the system from either the initial state of the specimen or the details of the process kinetics. Current limitations and prospects for the application of this method to improve the quality of SMA components are briefly discussed

Polar motion and UT1: Comparison of VLBI, lunar laser, satellite laser, satellite Doppler, and conventional astrometric determinations

Very long baseline interferometry observations made with a 3900 km baseline interferometer (Haystack Observatory in Massachusetts to Owens Valley Observation in California) were used to estimate changes in the X-component of the position of the Earth's pole and in UT1. These estimates are compared with corresponding ones from lunar laser ranging, satellite laser ranging, satellite Doppler, and stellar observations

Analyzing Prospects for Quantum Advantage in Topological Data Analysis

Lloyd et al. were first to demonstrate the promise of quantum algorithms for computing Betti numbers, a way to characterize topological features of data sets. Here, we propose, analyze, and optimize an improved quantum algorithm for topological data analysis (TDA) with reduced scaling, including a method for preparing Dicke states based on inequality testing, a more efficient amplitude estimation algorithm using Kaiser windows, and an optimal implementation of eigenvalue projectors based on Chebyshev polynomials. We compile our approach to a fault-tolerant gate set and estimate constant factors in the Toffoli complexity. Our analysis reveals that super-quadratic quantum speedups are only possible for this problem when targeting a multiplicative error approximation and the Betti number grows asymptotically. Further, we propose a dequantization of the quantum TDA algorithm that shows that having exponentially large dimension and Betti number are necessary, but insufficient conditions, for super-polynomial advantage. We then introduce and analyze specific problem examples which have parameters in the regime where super-polynomial advantages may be achieved, and argue that quantum circuits with tens of billions of Toffoli gates can solve seemingly classically intractable instances.Comment: 54 pages, 7 figures. Added a number of theorems and lemmas to clarify findings and also a discussion in the main text and new appendix about variants of our problems with high Betti numbers that are challenging for recent classical algorithm

An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment

Background: An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA).<p></p> Methods: A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements.<p></p> Results: Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05.<p></p> Conclusions: In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents’ preferences.<p></p&gt