Automatic generation of highly concurrent, hierarchical and heterogeneous cache coherence protocols from atomic specifications

Cache coherence protocols are often specified using only stable states and atomic transactions for a single cache hierarchy level. Designing highly-concurrent, hierarchical and heterogeneous directory cache coherence protocols from these atomic specifications for modern multicore architectures is a complicated task. To overcome these design challenges we have developed the novel *Gen algorithms (ProtoGen, HieraGen and HeteroGen). Using the *Gen algorithms highly-concurrent, hierarchical and heterogeneous cache coherence protocols can be automatically generated for a wide range of atomic input stable state protocol (SSP) speci fications - including the MOESI variants, as well as for protocols that are targeted towards Total Store Order and Release Consistency. In addition, for each *Gen algorithm we have developed and published an eponymous tool. The ProtoGen tool takes as input a single SSP (i.e., no concurrency) generating the corresponding protocol for a multicore architecture with non-atomic transactions. The ProtoGen algorithm automatically enforces the correct interleaving of conflicting coherence transactions for a given atomic coherence protocol specification. HieraGen is a tool for automatically generating hierarchical cache coherence protocols. Its inputs are SSPs for each level of the hierarchy and its output is a highly concurrent hierarchical protocol. HieraGen thus reduces the complexity that architects face by offloading the challenging task of composing protocols and managing concurrency. HeteroGen is a tool for automatically generating heterogeneous protocols that adhere to precise consistency models. As input, HeteroGen takes SSPs of the per-cluster coherence protocols, each of which satisfies its own per-cluster consistency model. The output is a concurrent (i.e., with transient states) heterogeneous protocol that satisfies a precisely defined consistency model that we refer to as a compound consistency model. To validate the correctness of the *Gen algorithms, the generated output protocols were verified for safety and deadlock freedom using a model checker. To verify the correctness of protocols that need to adhere to a specific compound consistency model generated by HeteroGen, novel litmus tests for multiple compound consistency models were developed. The protocols automatically generated using the *Gen tools have a comparable or better performance than manually generated cache coherence protocols, often discovering opportunities to reduce stalls. Thus, the *Gen tools reduce the complexity that architects face by offloading the challenging tasks of composing protocols and managing concurrency

AMAZON FRUIT

En la actualidad, el mundo entero está pasando por una situación excepcional y retadora. Esto se debe a la pandemia que ha tocado vivir atodos los ciudadanos en estos tiempos. Por ello, se ha visto necesario acceder a cuarentenas focalizadas para evitar cualquier tipo de contagios por el acercamiento o aglomeración de personas, ello ha ocasionado que varios negocios quiebren al disminuir notoriamente sus ingresos mensuales.En el presente trabajo, se busca la viabilidad de un servicio que mezcla las ventas online junto con productos que ayuden a levantar las defensas en las personas, especialmente en estos tiempos que se amerita estar muy bien alimentados. Lo que busca este proyecto es poder combatir los malos hábitos de consumo a través de frutos exóticos de la selva peruana que aporten vitaminas y/o nutrientes que mejoren el estilo de vida con fines sociales para comunidades de la selva peruana.Por ello, luego de realizar un proceso de idealización el cual permitió escoger la idea de negocio más asertiva, se realizó el modelo de negocio que permite una mayor descripción de nuestro proyecto. Posterior a ello, se realizaron experimentos para validar el mismo. Finalmente, se realizó el concierge con todos los resultados obtenidos de las validaciones y estrategias junto con los objetivos a desarrollar.Currently, the entire world is going through an exceptional and challenging situation. This is due to the pandemic that all citizens have experienced in these times. For this reason, it has been necessary to access focused quarantines to avoid any type of contagion due to the approach or agglomeration of people, this has caused several businesses to go bankrupt by significantly reducing their monthly income.This proyect triesto find the viability of a service that mixes online sales with products that helps to raise people's defenses is sought, especially in these times when it is necessary to be very well fed. This project seeks is to be able to combat bad consumption habits through exotic fruits from the Peruvian jungle that provide vitamins and / or nutrients that improve the lifestyle for social purposes for communities in the Peruvian jungle.Therefore, after carrying out an idealization process which allowed us to choose the most assertive business idea, the business model that allows a greater description of our project was created. After that, experiments were carried out to validate it. Finally, the concierge was held with all the results obtained from the validations and strategies together with the objectives to be developed.Trabajo de investigació

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