BP-NUCA: Cache Pressure-Aware Migration for High-Performance Caching in CMPs

As the momentum behind Chip Multi-Processors (CMPs) continues to grow, Last Level Cache (LLC) management becomes a crucial issue to CMPs because off-chip accesses often involve a big latency. Private cache design is distinguished by smaller local access latency, good performance isolation and easy scalability, thus is becoming an attractive design alternative for LLC of CMPs. This paper proposes Balanced Private Non-Uniform Cache Architecture (BP-NUCA), a new LLC architecture that starts from private cache design for smaller local access latency and good performance isolation, then introduces a low cost mechanism to dynamically migrate private blocks among peer private caches of LLC to improve the overall space utilization. BP-NUCA achieves this by measuring the cache access pressure level that each cache set experiences at runtime and then using the information to guide block migration among different private caches of LLC. A heavily accessed set, namely a set with high access pressure level, is allowed to migrate its evicted blocks to peer private caches, replacing blocks of sets which are with the same index and have low access pressure level. By migrating blocks from heavily accessed cache sets to less accessed cache sets, BP-NUCA effectively balances space utilization of LLC among different cores. Experimental results using a full system CMP simulator show that BP-NUCA improves the overall throughput by as much as 20.3 %, 12.4 %, 14.5 % and 18.0 % (on average 7.7 %, 4.4 %, 4.0 % and 6.1 %) over private cache, shared cache, shared cache management scheme UCP and private cache organization CC respectively on a 4-core CMP for SPEC CPU2006 benchmarks

Proposed Hydrogen-Bonding Index of Donor or Acceptor Reflecting Its Intrinsic Contribution to Hydrogen-Bonding Strength

In this work, we tentatively propose that the hydrogen-bonding strength <i>E</i>_HB (referring to the minimal hydrogen-bonding energy) and its corresponding hydrogen-bond (HB) distance (referring to the optimal HB distance <i>d</i>_HB) for simple mono-HB systems have an exponential relationship on the basis of MP2 and DFT computational results. We take a step further and propose that the hydrogen-bonding indices of the donor (<i>I</i>_donor) and acceptor (<i>I</i>_acceptor), reflecting their intrinsic contributions to hydrogen-bonding strength, also have an exponential relation with the hypothetical effective hydrogen-bond radii of the donor (<i>r</i>_donor) and acceptor (<i>r</i>_acceptor), respectively. On the basis of extensive quantum-mechanical calculations, relevant assumptions about the hydrogen-bonding index are rationalized. Moreover, the hydrogen-bonding index is also suggested as an additional prefiltering criterion for virtual screening besides the widely accepted Lipinski’s rule of five. Finally, a “Hydrogen-Bond Index Estimator (HBIE)” module has been implemented in our Visual Force Field Derivation Toolkit (VFFDT) program to approximately and rapidly estimate the hydrogen-bonding indices of any small molecules in batch and screen possible stronger donors or acceptors from the small-molecule database. To the best of our knowledge, the concept of the hydrogen-bonding index and its potential application are proposed here for the first time

Long-Term Infection and Pathogenesis in a Novel Mouse Model of Human Respiratory Syncytial Virus

Intensive efforts have been made to develop models of hRSV infection or disease using various animals. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we present a mouse model based on a Rag2 gene knockout using CRISPR/Cas9 technology. Rag2−/− mice sustained high viral loads upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1 × 109.8 copies/g and 1c106 TCID50 in nasal cavity, as well as 1 × 108 copies/g and 1 × 105 TCID50 in the lungs up to 5 weeks. Mild interstitial pneumonia, severe bronchopneumonia, elevated cytokines and NK cells were seen in Rag2−/− mice. A humanized monoclonal antibody showed strong antiviral activity in this animal model, implying that Rag2−/− mice that support long-term stable infection are a useful tool for studying the transmission and pathogenesis of human RSV, as well as evaluating therapeutics