An Anomalous Near-Bottom Cross-Shelf Intrusion of Slope Water on the Southern New England Continental Shelf

Hydrographic surveys and moored observations in Rhode Island Sound (RIS) in water depths of 30–50 m, off the southern New England coast, revealed a near-bottom intrusion of anomalously warm and saline water in late fall 2009. The properties of this water mass, with peak salinity of nearly 35, are typical of slope water that is normally found offshore of the shelfbreak front, located approximately 100 km to the south. The slope water intrusion, with a horizontal spatial scale of about 45 km, appears to have been brought onto the outer shelf during the interaction of a Gulf Stream warm core ring with the shelfbreak east (upshelf) of RIS. The along-shelf transport rate of the intrusion can be explained as due to advection by the mean outer-shelf along-isobath current, although the transit time of the intrusion is also consistent with the self-advection of a dense bolus on a sloping shelf. The mechanism responsible for the large onshore movement of the intrusion from the outer shelf is not entirely clear, although a wind-driven upwelling circulation appeared to be responsible for its final movement into the RIS region. Depth-averaged salinity at all RIS mooring sites increased by 0.5–1 over the 3–4 week intrusion period suggesting that the intrusion mixed irreversibly, at least partially, with the ambient shelf water. The mixing of the salty intrusion over the shelf indicates that net cross-isobath fluxes of salt and other water properties have occurred

The mentalistic basis of core social cognition: experiments in preverbal infants and a computational model

Evaluating individuals based on their pro- and anti-social behaviors is fundamental to successful human interaction. Recent research suggests that even preverbal infants engage in social evaluation; however, it remains an open question whether infants' judgments are driven uniquely by an analysis of the mental states that motivate others' helpful and unhelpful actions, or whether non-mentalistic inferences are at play. Here we present evidence from 10-month-olds, motivated and supported by a Bayesian computational model, for mentalistic social evaluation in the first year of life. A video abstract of this article can be viewed at http://youtu.be/rD_Ry5oqCY

GYM: A Multiround Distributed Join Algorithm

Multiround algorithms are now commonly used in distributed data processing systems, yet the extent to which algorithms can benefit from running more rounds is not well understood. This paper answers this question for several rounds for the problem of computing the equijoin of n relations. Given any query Q with width w, intersection width iw, input size IN, output size OUT, and a cluster of machines with M=Omega(IN frac{1}{epsilon}) memory available per machine, where epsilon > 1 and w ge 1 are constants, we show that: 1. Q can be computed in O(n) rounds with O(n(INw + OUT)2/M) communication cost with high probability. Q can be computed in O(log(n)) rounds with O(n(INmax(w, 3iw) + OUT)2/M) communication cost with high probability. Intersection width is a new notion we introduce for queries and generalized hypertree decompositions (GHDs) of queries that captures how connected the adjacent components of the GHDs are. We achieve our first result by introducing a distributed and generalized version of Yannakakis\u27s algorithm, called GYM. GYM takes as input any GHD of Q with width w and depth d, and computes Q in O(d + log(n)) rounds and O(n (INw + OUT)2/M) communication cost. We achieve our second result by showing how to construct GHDs of Q with width max(w, 3iw) and depth O(log(n)). We describe another technique to construct GHDs with longer widths and lower depths, demonstrating other tradeoffs one can make between communication and the number of rounds

Help or hinder: Bayesian models of social goal inference

Everyday social interactions are heavily influenced by our snap judgments about others’ goals. Even young infants can infer the goals of intentional agents from observing how they interact with objects and other agents in their environment: e.g., that one agent is ‘helping’ or ‘hindering’ another’s attempt to get up a hill or open a box. We propose a model for how people can infer these social goals from actions, based on inverse planning in multiagent Markov decision problems (MDPs). The model infers the goal most likely to be driving an agent’s behavior by assuming the agent acts approximately rationally given environmental constraints and its model of other agents present. We also present behavioral evidence in support of this model over a simpler, perceptual cue-based alternative.United States. Army Research Office (ARO MURI grant W911NF-08-1-0242)United States. Air Force Office of Scientific Research (MURI grant FA9550-07-1-0075)National Science Foundation (U.S.) (Graduate Research Fellowship)James S. McDonnell Foundation (Collaborative Interdisciplinary Grant on Causal Reasoning

Exploiting Overlapping Advantages of <i>in vitro</i> and <i>in cellulo</i> Selection Systems to Isolate a Novel High-affinity cJun Antagonist

We have combined two peptide library-screening systems, exploiting the benefits offered by both to select novel antagonistic agents of cJun. CIS display is an <i>in vitro</i> cell-free system that allows very large libraries (≤10¹⁴) to be interrogated. However, affinity-based screening conditions can poorly reflect those relevant to therapeutic application, particularly for difficult intracellular targets, and can lead to false positives. In contrast, an <i>in cellulo</i> screening system such as the Protein-fragment Complementation Assay (PCA) selects peptides with high target affinity while additionally profiling for target specificity, protease resistance, solubility, and lack of toxicity in a more relevant context. A disadvantage is the necessity to transform cells, limiting library sizes that can be screened to ≤10⁶. However, by combining both cell-free and cell-based systems, we isolated a peptide (CPW) from a ∼10¹⁰ member library, which forms a highly stable interaction with cJun (<i>T</i>_m = 63 °C, <i>K</i>_d = 750 nM, Δ<i>G</i> = −8.2 kcal/mol) using the oncogenic transcriptional regulator Activator Protein-1 (AP-1) as our exemplar target. In contrast, CIS display alone selected a peptide with low affinity for cJun (<i>T</i>_m = 34 °C, <i>K</i>_d = 25 μM, Δ<i>G</i> = −6.2 kcal/mol), highlighting the benefit of CIS → PCA. Furthermore, increased library size with CIS → PCA vs PCA alone allows the freedom to introduce noncanonical options, such as interfacial aromatics, and solvent exposed options that may allow the molecule to explore alternative structures and interact with greater affinity and efficacy with the target. CIS → PCA therefore offers significant potential as a peptide-library screening platform by synergistically combining the relative attributes of both assays to generate therapeutically interesting compounds that may otherwise not be identified

Codon-precise, synthetic, antibody fragment libraries built using automated hexamer codon additions and validated through next generation sequencing

We have previously described ProxiMAX, a technology that enables the fabrication of precise, combinatorial gene libraries via codon-by-codon saturation mutagenesis. ProxiMAX was originally performed using manual, enzymatic transfer of codons via blunt-end ligation. Here we present Colibra™: an automated, proprietary version of ProxiMAX used specifically for antibody library generation, in which double-codon hexamers are transferred during the saturation cycling process. The reduction in process complexity, resulting library quality and an unprecedented saturation of up to 24 contiguous codons are described. Utility of the method is demonstrated via fabrication of complementarity determining regions (CDR) in antibody fragment libraries and next generation sequencing (NGS) analysis of their quality and diversity

Athena: Advanced air launched space booster

The infrastructure for routine, reliable, and inexpensive access of space is a goal that has been actively pursued over the past 50 years, but has yet not been realized. Current launch systems utilize ground launching facilities which require the booster vehicle to plow up through the dense lower atmosphere before reaching space. An air launched system on the other hand has the advantage of being launched from a carrier aircraft above this dense portion of the atmosphere and hence can be smaller and lighter compared to its ground based counterpart. The goal of last year's Aerospace Engineering Course 483 (AE 483) was to design a 227,272 kg (500,000 lb.) air launched space booster which would beat the customer's launch cost on existing launch vehicles by at least 50 percent. While the cost analysis conducted by the class showed that this goal could be met, the cost and size of the carrier aircraft make it appear dubious that any private company would be willing to invest in such a project. To avoid this potential pitfall, this year's AE 483 class was to design as large an air launched space booster as possible which can be launched from an existing or modification to an existing aircraft. An initial estimate of the weight of the booster is 136,363 kg (300,000 lb.) to 159,091 kg (350,000 lb.)

Smoking in Systemic Sclerosis: a Longitudinal European Scleroderma Trials and Research Group Study

Data on the role of tobacco exposure in systemic sclerosis (SSc) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations in the EUSTAR database