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Huntington disease (HD) reflects the dominant consequences of a CAG-repeat expansion in HTT. Analysis of common SNP-based haplotypes has revealed that most European HD subjects have distinguishable HTT haplotypes on their normal and disease chromosomes and that ∼50% of the latter share the same major HD haplotype. We reasoned that sequence-level investigation of this founder haplotype could provide significant insights into the history of HD and valuable information for gene-targeting approaches. Consequently, we performed whole-genome sequencing of HD and control subjects from four independent families in whom the major European HD haplotype segregates with the disease. Analysis of the full-sequence-based HTT haplotype indicated that these four families share a common ancestor sufficiently distant to have permitted the accumulation of family-specific variants. Confirmation of new CAG-expansion mutations on this haplotype suggests that unlike most founders of human disease, the common ancestor of HD-affected families with the major haplotype most likely did not have HD. Further, availability of the full sequence data validated the use of SNP imputation to predict the optimal variants for capturing heterozygosity in personalized allele-specific gene-silencing approaches. As few as ten SNPs are capable of revealing heterozygosity in more than 97% of European HD subjects. Extension of allele-specific silencing strategies to the few remaining homozygous individuals is likely to be achievable through additional known SNPs and discovery of private variants by complete sequencing of HTT. These data suggest that the current development of gene-based targeting for HD could be extended to personalized allele-specific approaches in essentially all HD individuals of European ancestry.

Various social norms and legal restrictions limit individuals' autonomy based on their gender. Some of these restrict the romantic and sexual relationships individuals may pursue. Others restrict gender expression. Still others restrict the freedom to work, own property, or participate in the political process. Many scholars have studied the role of intentional political activism in combating these restrictions. Less explored, however, is how spontaneous order within market economies created opportunities for this type of activism. Individuals who are seeking private gains rather than social change can nonetheless contribute to social change that they do not intend. [ABSTRACT FROM AUTHOR]

The 2016 passage of California's Proposition 64, legalizing recreational (adult-use) cannabis, was justified ex ante in part for its potential to encourage restorative justice and positive local and state economic outcomes. But are the local institutions administering Proposition 64 achieving these aims? We address this question via a two-year case study of Mendocino County's polycentric cannabis governance system using a mixed methods approach including archival analysis, cannabis industry and governance system interviews, and participant observation. Evidence from our case study suggests that Mendocino's ability to achieve these goals is hampered by three quasi-market failures: interjurisdictional conflict, coproduction deficits, and devolution without adequate fiscal decentralization. A major driver in these quasi-market failures is the substantial regulatory and enforcement responsibility this governance system places on local government. We conclude by discussing some institutional structures that may address these failures. [ABSTRACT FROM AUTHOR]

We introduce and evaluate the concept of switched-element direction finding. In a switched-element system, simultaneous data collection occurs on only a subset of the array's N elements at any given time. The data collection interval is divided into subintervals, and at each subinterval a multiplexer selects a different subset of M < N elements to connect to the data acquisition channels. Since the switched-element system only collects data on M channels at a time, hardware costs can be reduced at the expense of a time-accuracy tradeoff compared to a full-channel system. We propose two algorithms. The first is a modification of the root-MVDR (minimum variance distortionless-response) algorithm that is appropriate for linear arrays and noncoherent sources. When sources are coherent, a second algorithm based on a compositely formed full-size covariance matrix is proposed. Although performance depends strongly on the number of sources, good performance can be obtained even when the number of sources is greater than M.

We propose to combine directional antennas in a conformal array configuration with a matching two-stage receiver architecture to improve performance of code-division multiple-access (CDMA) communication systems in time-varying channels. We propose a reduced-dimension space-time (ST) RAKE architecture that matches the ST correlation structure of the data received by a circular array. In time-varying channels, this reduced-dimension architecture outperforms the full-dimension architecture due to improved convergence of its adaptive processor. Index Terms--Multipath, multiuser detection, RAKE receiver, space-time beamforming.

We derive the generalized likelihood ratio test (GLRT) for multistatic space-time radar where each sensor platform has a coherent multi-channel array. A multistatic version of the adaptive matched filter (AMF) detector is also developed and its performance results compared with that of the GLRT. Results show that the multistatic GLRT outperforms the multistatic AMF and that the performance advantage increases with the number of radars in the system. The concepts of geometry gain and diversity gain for multistatic STAP are defined in terms of asymptotic properties of the system's probability of miss.

The likelihood ratio test (LRT) for multistatic detection is derived for the case where each sensor platform is a coherent space-time radar. Due to the geometric separation of the platforms, target statistics are modeled as independent from platform to platform but constant over the local data on a single platform. Clutter statistics are also assumed independent from platform to platform but have a local space-time correlation structure typical of monostatic space-time adaptive processing (STAP). Moreover, the target Doppler hypothesis varies from platform to platform due to multiple viewing perspectives. Previous published work has investigated the detection improvement obtained by multiple input, multiple output (MIMO) radar. This prior work, however, has only considered white noise. When clutter is considered, the diversity benefit of a MIMO or multistatic radar system is strongly dependent on geometry. We investigate the relationship between geometry and diversity gain for multistatic airborne space-time radar and the effects of this relationship on decentralized and centralized detection.