More Like this

1. Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

   https://doi.org/10.1128/JB.00872-15  

   Baker, Anna W.; Satyshur, Kenneth A.; Moreno Morales, Neydis; Forest, Katrina T.; Stock, A. M. (March 2016, Journal of Bacteriology)

   ABSTRACT Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacterium Ramlibacter tataouinensis . RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, the R. tataouinensis bacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR from Agrobacterium tumefaciens , crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRR mon ) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems. IMPORTANCE BphP histidine kinases and their cognate response regulators comprise widespread red light-sensing two-component systems. Much work on BphPs has focused on structural understanding of light sensing and on enhancing the natural infrared fluorescence of these proteins, rather than on signal transduction or the resultant phenotypes. To begin to address this knowledge gap, we solved the crystal structures of two single-domain response regulators encoded by a region immediately downstream of that encoding BphPs. We observed a previously unknown arm-in-arm dimer linkage. Monomerization via deletion of the C-terminal dimerization motif had an inhibitory effect on net response regulator phosphorylation, underlining the importance of these unusual dimers for signal transduction. 

   more » « less
2. ARM Virtualization: Performance and Architectural Implications

   https://doi.org/10.1145/3273982.3273987  

   Dall, Christoffer; Li, Shih-Wei; Lim, Jin Tack; Nieh, Jason (July 2018, Operating systems review)

   ARM servers are becoming increasingly common, making server technologies such as virtualization for ARM of growing importance. We present the first study of ARM virtualization performance on server hardware, including multi-core measurements of two popular ARM and x86 hypervisors, KVM and Xen. We show how ARM hardware support for virtualization can enable much faster transitions between VMs and the hypervisor, a key hypervisor operation. However, current hypervisor designs, including both Type 1 hypervisors such as Xen and Type 2 hypervisors such as KVM, are not able to leverage this performance benefit for real application workloads on ARMv8.0. We discuss the reasons why and show that other factors related to hypervisor software design and implementation have a larger role in overall performance. Based on our measurements, we discuss software changes and new hardware features, the Virtualization Host Extensions (VHE), added in ARMv8.1 that bridge the gap and bring ARM's faster VM-to-hypervisor transition mechanism to modern Type 2 hypervisors running real applications. 

   more » « less
3. Design and Verification of the Arm Confidential Compute Architecture

   Li, Xupeng; Li, Xuheng; Dall, Christoffer; Gu, Ronghui; Nieh, Jason; Sait, Yousuf; Stockwell, Gareth (July 2022, Proceedings of the 16th USENIX Symposium on Operating Systems Design and Implementation (OSDI 2022))
4. Top Feasible Arm Identification

   Katz-Samuels, Julian; Scott, Clayton (January 2019, Proceedings of the 22nd International Conference on Artificial Intelligence and Statistics (AISTATS))

   We propose a new variant of the top arm identification problem, top feasible arm identification, where there are K arms associated with D-dimensional distributions and the goal is to find m arms that maximize some known linear function of their means subject to the constraint that their means belong to a given set P € R D. This problem has many applications since in many settings, feedback is multi-dimensional and it is of interest to perform constrained maximization. We present problem-dependent lower bounds for top feasible arm identification and upper bounds for several algorithms. Our most broadly applicable algorithm, TF-LUCB-B, has an upper bound that is loose by a factor of OpDlogpKqq. Many problems of practical interest are two dimensional and, for these, it is loose by a factor of OplogpKqq. Finally, we conduct experiments on synthetic and real-world datasets that demonstrate the effectiveness of our algorithms. Our algorithms are superior both in theory and in practice to a naive two-stage algorithm that first identifies the feasible arms and then applies a best arm identification algorithm to the feasible arms. 

   more » « less
5. Robust Outlier Arm Identification

   Zhu, Yinglun; Katariya, Sumeet; Nowak, Robert (July 2020, International Conference on Machine Learning)

   We study the problem of Robust Outlier Arm Identification (ROAI), where the goal is to identify arms whose expected rewards deviate substantially from the majority, by adaptively sampling from their reward distributions. We compute the outlier threshold using the median and median absolute deviation of the expected rewards. This is a robust choice for the threshold compared to using the mean and standard deviation, since it can identify outlier arms even in the presence of extreme outlier values. Our setting is different from existing pure exploration problems where the threshold is pre-specified as a given value or rank. This is useful in applications where the goal is to identify the set of promising items but the cardinality of this set is unknown, such as finding promising drugs for a new disease or identifying items favored by a population. We propose two 𝛿 -PAC algorithms for ROAI, which includes the first UCB-style algorithm for outlier detection, and derive upper bounds on their sample complexity. We also prove a matching, up to logarithmic factors, worst case lower bound for the problem, indicating that our upper bounds are generally unimprovable. Experimental results show that our algorithms are both robust and about 5 x sample efficient compared to state-of-the-art. 

   more » « less