The Variational Method of Moments

The conditional moment problem is a powerful formulation for describing structural causal parameters in terms of observables, a prominent example being instrumental variable regression. A standard approach is to reduce the problem to a finite set of marginal moment conditions and apply the optimally weighted generalized method of moments (OWGMM), but this requires we know a finite set of identifying moments, can still be inefficient even if identifying, or can be theoretically efficient but practically unwieldy if we use a growing sieve of moment conditions. Motivated by a variational minimax reformulation of OWGMM, we define a very general class of estimators for the conditional moment problem, which we term the variational method of moments (VMM) and which naturally enables controlling infinitely-many moments. We provide a detailed theoretical analysis of multiple VMM estimators, including ones based on kernel methods and neural nets, and provide appropriate conditions under which these estimators are consistent, asymptotically normal, and semiparametrically efficient in the full conditional moment model. This is in contrast to other recently proposed methods for solving conditional moment problems based on adversarial machine learning, which do not incorporate optimal weighting, do not establish asymptotic normality, and are not semiparametrically efficient. In addition, we provide corresponding inference algorithms based on the same kind of variational reformulations, both for kernel- and neural net-based varieties. Finally, we demonstrate the strong performance of our proposed estimation and inference algorithms in a detailed series of synthetic experiments

Mapping the mammalian ribosome quality control complex interactome using proximity labeling approaches.

Previous genetic and biochemical studies from Saccharomyces cerevisiae have identified a critical ribosome-associated quality control complex (RQC) that facilitates resolution of stalled ribosomal complexes. While components of the mammalian RQC have been examined in vitro, a systematic characterization of RQC protein interactions in mammalian cells has yet to be described. Here we utilize both proximity-labeling proteomic approaches, BioID and APEX, and traditional affinity-based strategies to both identify interacting proteins of mammalian RQC members and putative substrates for the RQC resident E3 ligase, Ltn1. Surprisingly, validation studies revealed that a subset of substrates are ubiquitylated by Ltn1 in a regulatory manner that does not result in subsequent substrate degradation. We demonstrate that Ltn1 catalyzes the regulatory ubiquitylation of ribosomal protein S6 kinase 1 and 2 (RPS6KA1, RPS6KA3). Further, loss of Ltn1 function results in hyperactivation of RSK1/2 signaling without impacting RSK1/2 protein turnover. These results suggest that Ltn1-mediated RSK1/2 ubiquitylation is inhibitory and establishes a new role for Ltn1 in regulating mitogen-activated kinase signaling via regulatory RSK1/2 ubiquitylation. Taken together, our results suggest that mammalian RQC interactions are difficult to observe and may be more transient than the homologous complex in S. cerevisiae and that Ltn1 has RQC-independent functions

Scoping study on migrant fishers and transboundary fishing in the Bay of Bengal

This study assesses the issue of migratory and transboundary fishing. It explores working conditions on fishing vessels operating outside national waters together with issues pertaining to rights and extent of use of legal and illegal foreign labour. The report also provides recommendations for action and further research

Would You Live Here? Making the Growth Areas communities of choice

This book aims to promote a better understanding of who will live in the Growth Areas, what their aspirations and needs will be, and how we can meet them

Conservation, community benefit, capacity buliding and the social economy : a case study of Lutsel K'e and the proposed national park

In 2001, 32 years after the Government of Canada initially proposed a national park on the East Arm of Great Slave Lake in the traditional territory of the Lutsel K'e Dene First Nation, Chief Felix Lockhart indicated to Parks Canada that the community was interested in discussing the idea. In 2006, an MOU was signed between the Government of Canada and the Lutsel K'e Dene First Nation that has lead to the withdrawal of an area of 33,525 km2 while studies, negotiations and consultations take place