Improving Multiple-CMP Systems Using Token Coherence

Improvements in semiconductor technology now enable Chip Multiprocessors (CMPs). As many future computer systems will use one or more CMPs and support shared memory, such systems will have caches that must be kept coherent. Coherence is a particular challenge for Multiple-CMP (M-CMP) systems. One approach is to use a hierarchical protocol that explicitly separates the intra-CMP coherence protocol from the inter-CMP protocol, but couples them hierarchically to maintain coherence. However, hierarchical protocols are complex, leading to subtle, difficult-to-verify race conditions. Furthermore, most previous hierarchical protocols use directories at one or both levels, incurring indirections—and thus extra latency—for sharing misses, which are common in commercial workloads. In contrast, this paper exploits the separation of correctness substrate and performance policy in the recently-proposed token coherence protocol to develop the first M-CMP coherence protocol that is flat for correctness, but hierarchical for performance. Via model checking studies, we show that flat correctness eases verification. Via simulation with micro-benchmarks, we make new protocol variants more robust under contention. Finally, via simulation with commercial workloads on a commercial operating system, we show that new protocol variants can be 10-50% faster than a hierarchical directory protocol

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Toward a Decidable Notion of Sequential Consistency

A memory model specifies a correctness requirement for a distributed shared memory protocol. Sequential consistency (SC) is the most widely researched model; previous work [1] has shown that, in general, the SC verification problem is undecidable. We identify two aspects of the formulation found in [1] that we consider to be highly unnatural; we call these non-prefix-closedness and prophetic inheritance. We conjecture that preclusion of such behavior yields a decidable version of SC, which we call decisive sequential consistency (DSC). We also introduce a structure called a view window (VW), which retains information about a protocol&apos;s history, and we define the notion of a VW-bound, which essentially bounds the size of the VWs needed to maintain DSC. We prove that the class of DSC protocols with VW-bound k is decidable; left conjectured is the hypothesis that all DSC protocols have such a bound, and further that the bound is computable from the protocol description. This hypothesis is true for all real protocols known to us; we verify its truth for the Lazy Caching protocol [2]

Abstract Improvements in semiconductor technology now

computer systems will use one or more CMPs and support shared memory, such systems will have caches that must be kept coherent. Coherence is a particular challenge for Multiple-CMP (M-CMP) systems. One approach is to use a hierarchical protocol that explicitly separates the intra-CMP coherence protocol from the inter-CMP protocol, but couples them hierarchically to maintain coherence. However, hierarchical protocols are complex, leading to subtle, difficult-to-verify race conditions. Furthermore, most previous hierarchical protocols use directories at one or both levels, incurring indirections—and thus extra latency—for sharing misses, which are common in commercial workloads. In contrast, this paper exploits the separation of correctness substrate and performance policy in the recently-proposed token coherence protocol to develop the first M-CMP coherence protocol that is flat for correctness, but hierarchical for performance. Via model checking studies, we show that flat correctness eases verification. Via simulation with micro-benchmarks, we make new protocol variants more robust under contention. Finally, via simulation with commercial workloads on a commercial operating system, we show that new protocol variants can be 10-50 % faster than a hierarchical directory protocol.

Community Survey after Rabies Outbreaks, Flagstaff, Arizona, USA

Educational outreach should inform the public about dangers of translocation of wild animals and general aspects of rabies

Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap

An ideal surface-enhanced Raman scattering (SERS) nanostructure for sensing and imaging applications should induce a high signal enhancement, generate a reproducible and uniform response, and should be easy to synthesize. Many SERSactive nanostructures have been investigated, but they suffer from poor reproducibility of the SERS-active sites, and the wide distribution of their enhancement factor values results in an unquantifiable SERS signal. Here, we show that DNA on gold nanoparticles facilitates the formation of well-defined gold nanobridged nanogap particles (Au-NNP) that generate a highly stable and reproducible SERS signal. The uniform and hollow gap (similar to 1 nm) between the gold core and gold shell can be precisely loaded with a quantifiable amount of Raman dyes. SERS signals generated by Au-NNPs showed a linear dependence on probe concentration (R(2) &gt; 0.98) and were sensitive down to 10 fM concentrations. Single-particle nano-Raman mapping analysis revealed that &gt;90% of Au-NNPs had enhancement factors greater than 1.0 x 10(8), which is sufficient for single-molecule detection, and the values were narrowly distributed between 1.0 x 10(8) and 5.0 x 10(9)

Weder ein „modern gender gap“ noch „same gender voting“ in Deutschland? Zum Einfluss des Geschlechts auf das individuelle Wahlverhalten bei den Bundestagswahlen zwischen 1998 und 2013

Der Beitrag geht der Frage nach, ob ein Einfluss des Geschlechts auf die Wahlabsicht bei Wahlen zum Deutschen Bundestag zwischen 1998 und 2013 vorliegt. Auf der Grundlage der Literatur zum „modern gender gap“ einerseits sowie zum „same gender voting“ anderseits werden Hypothesen dahingehend abgeleitet, dass Frauen einen geringeren Anreiz haben sollten, christdemokratische Parteien zu wählen, und dass – als gegenläufige Erwartung – mit der Kanzlerkandidatur Angela Merkels seit 2005 Frauen verstärkt CDU oder CSU wählen sollten. Es zeigt sich weder ein durchgängiger Effekt für ein interessegeleitetes Wählen von Frauen, das sich in einer signifikant niedrigeren Wahrscheinlichkeit der Wahl der Unionsparteien hätte äußern sollen, noch Evidenz dafür, dass Frauen ab 2005 aufgrund der Kanzlerkandidatur Angela Merkels verstärkt CDU und CSU unterstützt haben. Lediglich 2013 zeigt sich in Westdeutschland eine Tendenz für den letztgenannten Zusammenhang. Demnach spielt das Geschlecht eines Wählers für die Wahlabsicht bei Bundestagswahlen kaum eine ausschlaggebende Rolle