Mutations in Mtr4 Structural Domains Reveal Their Important Role in Regulating tRNA\u3csub\u3ei\u3c/sub\u3e \u3csup\u3eMet\u3c/sup\u3e Turnover in \u3cem\u3eSaccharomyces cerevisiae\u3c/em\u3e and Mtr4p Enzymatic Activities \u3cem\u3eIn Vitro\u3c/em\u3e

RNA processing and turnover play important roles in the maturation, metabolism and quality control of a large variety of RNAs thereby contributing to gene expression and cellular health. The TRAMP complex, composed of Air2p, Trf4p and Mtr4p, stimulates nuclear exosome-dependent RNA processing and degradation in Saccharomyces cerevisiae. The Mtr4 protein structure is composed of a helicase core and a novel so-called arch domain, which protrudes from the core. The helicase core contains highly conserved helicase domains RecA-1 and 2, and two structural domains of unclear functions, winged helix domain (WH) and ratchet domain. How the structural domains (arch, WH and ratchet domain) coordinate with the helicase domains and what roles they are playing in regulating Mtr4p helicase activity are unknown. We created a library of Mtr4p structural domain mutants for the first time and screened for those defective in the turnover of TRAMP and exosome substrate, hypomodified tRNAiMet. We found these domains regulate Mtr4p enzymatic activities differently through characterizing the arch domain mutants K700N and P731S, WH mutant K904N, and ratchet domain mutant R1030G. Arch domain mutants greatly reduced Mtr4p RNA binding, which surprisingly did not lead to significant defects on either in vivo tRNAiMet turnover, or in vitro unwinding activities. WH mutant K904N and Ratchet domain mutant R1030G showed decreased tRNAiMet turnover in vivo, as well as reduced RNA binding, ATPase and unwinding activities of Mtr4p in vitro. Particularly, K904 was found to be very important for steady protein levels in vivo. Overall, we conclude that arch domain plays a role in RNA binding but is largely dispensable for Mtr4p enzymatic activities, however the structural domains in the helicase core significantly contribute to Mtr4p ATPase and unwinding activities

Heavy-tailed Independent Component Analysis

Independent component analysis (ICA) is the problem of efficiently recovering a matrix $A \in \mathbb{R}^{n\times n}$ from i.i.d. observations of $X=AS$ where $S \in \mathbb{R}^n$ is a random vector with mutually independent coordinates. This problem has been intensively studied, but all existing efficient algorithms with provable guarantees require that the coordinates $S_i$ have finite fourth moments. We consider the heavy-tailed ICA problem where we do not make this assumption, about the second moment. This problem also has received considerable attention in the applied literature. In the present work, we first give a provably efficient algorithm that works under the assumption that for constant $\gamma > 0$, each $S_i$ has finite $(1+\gamma)$-moment, thus substantially weakening the moment requirement condition for the ICA problem to be solvable. We then give an algorithm that works under the assumption that matrix $A$ has orthogonal columns but requires no moment assumptions. Our techniques draw ideas from convex geometry and exploit standard properties of the multivariate spherical Gaussian distribution in a novel way.Comment: 30 page

Trauma and acute care surgeons report prescribing less opioids over time.

IntroductionConfronted with the opioid epidemic, surgeons must play a larger role to reduce risk of opioid abuse while managing acute pain. Having a better understanding of the beliefs and practices of trauma and acute care surgeons regarding discharge pain management may offer potential targets for interventions beyond fixed legal mandates.MethodsAn Institutional Review Board-approved electronic survey was sent to trauma and acute care surgeons who are members of the American Association for the Surgery of Trauma, and trauma and acute care surgeons and nurse practitioners at a Level 1 trauma center in February 2018. The survey included four case-based scenarios and questions about discharge prescription practices and beliefs.ResultsOf 66 respondents, most (88.1%) were at academic institutions. Mean number of opioid tablets prescribed was 20-30 (range 5-90), with the fewest tablets prescribed for elective laparoscopic cholecystectomy and the most for rib fractures. Few prescribed both opioid and non-opioid medications (22.4% to 31.4 %). Most would not change the number/strength of medications (69.2%), dose (53.9%), or number of tablets of opioids (83.1%) prescribed if patients used opioids regularly prior to their operation. The most common factors that made providers more likely to prescribe opioids were high inpatient opioid use (32.4%), history of opioid use/abuse (24.5%), and if the patient lives far from the hospital (12.9%). Most providers in practice >5 years reported a decrease in opioids (71.9%) prescribed at discharge.ConclusionTrauma and acute care surgeons and nurse practitioners reported decreasing the number/amount of opioids prescribed over time. Patients with high opioid use in the hospital, history of opioid use/abuse, or who live far from the provider may be prescribed more opioids at discharge.Level of evidenceLevel IV

Book review: cold war anthropology: the CIA, the Pentagon and the growth of dual use anthropology by David H. Price

In Cold War Anthropology: The CIA, The Pentagon and the Growth of Dual Use Anthropology, David H. Price offers a historical account of how the CIA, The Pentagon and the broader US military industrial complex have had a profound influence on the development of US anthropology during the Cold War and into the present day. This dense, readable work outlines and confronts how ethnographic research in the field has been shaped by wider political-economic forces; Joseph Anderson therefore encourages anthropologists to consider and discuss its implications with colleagues and students