The Crystal Structure of Monovalent Streptavidin.

The strong interaction between streptavidin (SA) and biotin is widely utilized in biotechnological applications. A SA variant, monovalent SA, was developed with a single and high affinity biotin-binding site within the intact tetramer. However, its structural characterization remains undetermined. Here, we seek to determine the crystal structure of monovalent SA at 1.7-Å resolution. We show that, in contrast to its 'close-state' in the only wild-type subunit, the L3,4 loops of three Dead SA subunits are free from crystal packing and remain in an 'open state', stabilized by a consistent H-bonding network involving S52. This H-bonding network also applies to the previously reported open state of the wild-type apo-SA. These results suggest that specific substitutions (N23A/S27D/S45A) at biotin-binding sites stabilize the open state of SA L3,4 loop, thereby further reducing biotin-binding affinity. The general features of the 'open state' SA among different SA variants may facilitate its rational design. The structural information of monovalent SA will be valuable for its applications across a wide range of biotechnological areas

Adaptive Network Coding for Scheduling Real-time Traffic with Hard Deadlines

We study adaptive network coding (NC) for scheduling real-time traffic over a single-hop wireless network. To meet the hard deadlines of real-time traffic, it is critical to strike a balance between maximizing the throughput and minimizing the risk that the entire block of coded packets may not be decodable by the deadline. Thus motivated, we explore adaptive NC, where the block size is adapted based on the remaining time to the deadline, by casting this sequential block size adaptation problem as a finite-horizon Markov decision process. One interesting finding is that the optimal block size and its corresponding action space monotonically decrease as the deadline approaches, and the optimal block size is bounded by the "greedy" block size. These unique structures make it possible to narrow down the search space of dynamic programming, building on which we develop a monotonicity-based backward induction algorithm (MBIA) that can solve for the optimal block size in polynomial time. Since channel erasure probabilities would be time-varying in a mobile network, we further develop a joint real-time scheduling and channel learning scheme with adaptive NC that can adapt to channel dynamics. We also generalize the analysis to multiple flows with hard deadlines and long-term delivery ratio constraints, devise a low-complexity online scheduling algorithm integrated with the MBIA, and then establish its asymptotical throughput-optimality. In addition to analysis and simulation results, we perform high fidelity wireless emulation tests with real radio transmissions to demonstrate the feasibility of the MBIA in finding the optimal block size in real time.Comment: 11 pages, 13 figure

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro-oncogenic, typically depending on the cellular context. Squamous cell carcinoma (SCC) is a cancer of the squamous cell, which can occur in diverse human tissues. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers

Under-reaction in the Sovereign CDS Market

The sovereign CDS market has been growing rapidly in recent years, with a gross notional amount of around 2 trillion dollars in 2015. We document a strong momentum effect in this market. Its unique feature is that this momentum strategy returns are positively skewed and higher during recessions. Hence, this effect cannot be attributed to momentum crash risk or exposure to business cycles. Our evidence is consistent with the interpretation that the effect is due to investors’ initial underreaction to sovereign credit information followed by corrections, especially during public announcements of credit rating or outlook changes of the underlying countries

Global Perspective or Local Knowledge: The Macro-Information in the Sovereign CDS Market

This paper shows that sovereign CDS spreads can predict future stock index returns, sovereign bond yields, as well as real macroeconomic variables such as GDP and PMI. The predictive power comes almost entirely from the global, rather than country-specific, component of sovereign CDS spreads. This is consistent with the interpretation that the information advantage of sovereign CDS investors is derived from their global perspective rather than their local knowledge about individual countries. Stock and sovereign bond market indices gradually “catch up” with sovereign CDS spreads, mostly during the days surrounding credit rating or outlook changes, and especially for downgrades