Extending the VEF traces framework to model data center network workloads

Producción CientíficaData centers are a fundamental infrastructure in the Big-Data era, where applications and services demand a high amount of data and minimum response times. The interconnection network is an essential subsystem in the data center, as it must guarantee high communication bandwidth and low latency to the communication operations of applications, otherwise becoming the system bottleneck. Simulation is widely used to model the network functionality and to evaluate its performance under specific workloads. Apart from the network modeling, it is essential to characterize the end-nodes communication pattern, which will help identify bottlenecks and flaws in the network architecture. In previous works, we proposed the VEF traces framework: a set of tools to capture communication traffic of MPI-based applications and generate traffic traces used to feed network simulator tools. In this paper, we extend the VEF traces framework with new communication workloads such as deep-learning training applications and online data-intensive workloads.Ministerio de Ciencia e Innovación y Agencia Estatal de Investigación (MCIN/AEI/10.13039/501100011033) R &D Project Grant (PID2019-109001RA-I00)Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Energy efficient HPC network topologies with on/off links

Producción CientíficaEnergy efficiency is a must in today HPC systems. To achieve this goal, a holistic design based on the use of power-aware components should be performed. One of the key components of an HPC system is the high-speed interconnect. In this paper, we compare and evaluate several design options for the interconnection network of an HPC system, including torus, fat-trees and dragonflies. State of the art low power modes are also used in the interconnection networks. The paper does not only consider energy efficiency at the interconnection network level but also at the system as a whole. The analysis is performed by using a simple yet realistic power model of the system. The model has been adjusted using actual power consumption values measured on a real system. Using this model, realistic multi-job trace-based workloads have been used, obtaining the execution time and energy consumed. The results are presented to ease choosing a system, depending on which parameter, performance or energy consumption, receives the most importance.Ministerio de Economía, Industria y Competitividad (projects PID2019-105903RB-100 and PID2021-123627OB)Junta de Comunidades de Castilla-La Mancha (project SBPLY/21/180501/ 000248

Energy efficient torus networks with on/off links

[EN] Future exascale computing systems will require energy and performance efficient interconnection networks to respond to the high data movement demands of new applications, such as those coming from big-data and artificial intelligence areas. The network structure plays a major role in the overall interconnect performance, for this reason torus is a common topology used in the current largest supercomputers. There are several proposals to improve energy efficiency of interconnection networks. However, few works combine both energy and performance, and sometimes they are treated as opposed issues. In this paper, we try to determine which torus network configuration offers the best performance/energy ratio when high-radix switches are used to build the interconnect system. The performance/energy evaluation has been performed by trace-driven simulation under realistic scenarios, where several mixes of scientific applications share a supercomputer system and are scheduled to be executed with the available resources at each moment.This work has been supported by the Spanish MINECO and European Commission (FEDER funds) under project TIN2015-66972-05-1-R and project TIN2015-66972-05-2-R. Francisco J. Andujar is also funded by the Spanish MINECO under a Juan de la Cierva grant FJCI-2015-26080.Andújar, FJ.; Coll, S.; Alonso Díaz, M.; Martínez-Rubio, J.; López Rodríguez, PJ.; Sánchez, JL.; Alfaro, FJ.... (2019). Energy efficient torus networks with on/off links. Journal of Parallel and Distributed Computing. 130:37-49. https://doi.org/10.1016/j.jpdc.2019.03.015S374913

Energy efficient HPC network topologies with on/off links

[EN] Energy efficiency is a must in today HPC systems. To achieve this goal, a holistic design based on the use of power-aware components should be performed. One of the key components of an HPC system is the high-speed interconnect. In this paper, we compare and evaluate several design options for the interconnection network of an HPC system, including torus, fat-trees and dragonflies. State of the art low power modes are also used in the interconnection networks. The paper does not only consider energy efficiency at the interconnection network level but also at the system as a whole.The analysis is performed by using a simple yet realistic power model of the system. The model has been adjusted using actual power consumption values measured on a real system. Using this model, realistic multi-job trace-based workloads have been used, obtaining the execution time and energy consumed. The results are presented to ease choosing a system, depending on which parameter, performance or energy consumption, receives the most importance.This work has been supported by the Spanish Ministerio de Ciencia e Innovacion (MICINN, formerly MINECO) , and the European Commission (FEDER funds) under the projects PID2019- 105903RB-100 and PID2021-123627OB-C5, and by Junta de Comunidades de Castilla -La Mancha under the project SBPLY/21/180501/000248.Andújar-Muñoz, FJ.; Coll, S.; Alonso Díaz, M.; Martínez-Rubio, J.; López Rodríguez, PJ.; Sánchez García, JL.; Alfaro Cortés, FJ. (2023). Energy efficient HPC network topologies with on/off links. Future Generation Computer Systems. 139:126-138. https://doi.org/10.1016/j.future.2022.09.01212613813

Actionable cancer vulnerability due to translational arrest, p53 aggregation and ribosome biogenesis stress evoked by the disulfiram metabolite CuET.

We would like to thank M.Oren (Weizmann Institute of Science) for kindly providing the MDM2 antibodies, the core facility for Bioinformatics and Expression Analysis (BEA, Karolinska, Huddinge) for assisting in massive parallel sequencing and computational infrastructure, as well as E Dratkiewicz, AS Nilsson, and JF Martinez for excellent technical assistance.Drug repurposing is a versatile strategy to improve current therapies. Disulfiram has long been used in the treatment of alcohol dependency and multiple clinical trials to evaluate its clinical value in oncology are ongoing. We have recently reported that the disulfiram metabolite diethyldithiocarbamate, when combined with copper (CuET), targets the NPL4 adapter of the p97VCP segregase to suppress the growth of a spectrum of cancer cell lines and xenograft models in vivo. CuET induces proteotoxic stress and genotoxic effects, however important issues concerning the full range of the CuET-evoked tumor cell phenotypes, their temporal order, and mechanistic basis have remained largely unexplored. Here, we have addressed these outstanding questions and show that in diverse human cancer cell models, CuET causes a very early translational arrest through the integrated stress response (ISR), later followed by features of nucleolar stress. Furthermore, we report that CuET entraps p53 in NPL4-rich aggregates leading to elevated p53 protein and its functional inhibition, consistent with the possibility of CuET-triggered cell death being p53-independent. Our transcriptomics profiling revealed activation of pro-survival adaptive pathways of ribosomal biogenesis (RiBi) and autophagy upon prolonged exposure to CuET, indicating potential feedback responses to CuET treatment. The latter concept was validated here by simultaneous pharmacological inhibition of RiBi and/or autophagy that further enhanced CuET's tumor cytotoxicity, using both cell culture and zebrafish in vivo preclinical models. Overall, these findings expand the mechanistic repertoire of CuET's anti-cancer activity, inform about the temporal order of responses and identify an unorthodox new mechanism of targeting p53. Our results are discussed in light of cancer-associated endogenous stresses as exploitable tumor vulnerabilities and may inspire future clinical applications of CuET in oncology, including combinatorial treatments and focus on potential advantages of using certain validated drug metabolites, rather than old, approved drugs with their, often complex, metabolic profiles.This work was funded by the following grants: the Swedish Cancer Society (grant number: 170176), the Swedish Research Council (VR-MH 2014-46602-117891-30), Novo Nordisk Foundation (NNF20OC0060590), Danish National Research Foundation (project CARD, DNRF 125), the Danish Cancer Society (R204-A12617-B153), DFF 1026-00241B (all granted to JB), and the Grant agency of the Czech Republic: GACR 20-28685S (granted to ZS and MM). Open access funding provided by Karolinska Institute.S

TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity

Topoisomerase IIβ-binding protein 1 (TOPBP1) participates in DNA replication and DNA damage response; however, its role in DNA repair and relevance for human cancer remain unclear. Here, through an unbiased small interfering RNA screen, we identified and validated TOPBP1 as a novel determinant whose loss sensitized human cells to olaparib, an inhibitor of poly(ADP-ribose) polymerase. We show that TOPBP1 acts in homologous recombination (HR) repair, impacts olaparib response, and exhibits aberrant patterns in subsets of human ovarian carcinomas. TOPBP1 depletion abrogated RAD51 loading to chromatin and formation of RAD51 foci, but without affecting the upstream HR steps of DNA end resection and RPA loading. Furthermore, TOPBP1 BRCT domains 7/8 are essential for RAD51 foci formation. Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase–mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin. Overall, our results provide mechanistic insights into TOPBP1’s role in HR, with potential clinical implications for cancer treatment

Results of a survey on peri-operative nutritional support in pancreatic and biliary surgery in Spain

Introduction: a survey on peri-operative nutritional support in pancreatic and biliary surgery among Spanish hospitals in 2007 showed that few surgical groups followed the 2006 ESPEN guidelines. Ten years later we sent a questionnaire to check the current situation. Methods: a questionnaire with 21 items sent to 38 centers, related to fasting time before and after surgery, nutritional screening use and type, time and type of peri-operative nutritional support, and number of procedures. Results: thirty-four institutions responded. The median number of pancreatic resections (head/total) was 29.5 (95 % CI: 23.0-35; range, 5-68) (total, 1002); of surgeries for biliary malignancies (non-pancreatic), 9.8 (95 % CI: 7.3-12.4; range, 2-30); and of main biliary resections for benign conditions, 10.4 (95 % CI: 7.6-13.3; range, 2-33). Before surgery, only 41.2 % of the sites used nutritional support (< 50 % used any nutritional screening procedure). The mean duration of preoperative fasting for solid foods was 9.3 h (range, 6-24 h); it was 6.6 h for liquids (range, 2-12). Following pancreatic surgery, 29.4 % tried to use early oral feeding, but 88.2 % of the surveyed teams used some nutritional support; 26.5 % of respondents used TPN in 100 % of cases. Different percentages of TPN and EN were used in the other centers. In malignant biliary surgery, 22.6 % used TPN always, and EN in 19.3 % of cases. Conclusions: TPN is the commonest nutrition approach after pancreatic head surgery. Only 29.4 % of the units used early oral feeding, and 32.3 % used EN; 22.6 % used TPN regularly after surgery for malignant biliary tumours. The 2006 ESPEN guideline recommendations are not regularly followed 12 years after their publication in our country

Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID)

Background: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. Methods: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. Results: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). Conclusions: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival. (C) 2021 The Authors. Published by Elsevier Ltd

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID)

Background and objectives: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease -free survival. Methods: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. Results: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). Conclusion: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection

Resultados de una encuesta sobre el soporte nutricional perioperatorio en la cirugía pancreática y biliar en España

Introduction: a survey on peri-operative nutritional support in pancreatic and biliary surgery among Spanish hospitals in 2007 showed that few surgical groups followed the 2006 ESPEN guidelines. Ten years later we sent a questionnaire to check the current situation. Methods: a questionnaire with 21 items sent to 38 centers, related to fasting time before and after surgery, nutritional screening use and type, time and type of peri-operative nutritional support, and number of procedures. Results: thirty-four institutions responded. The median number of pancreatic resections (head/total) was 29.5 (95% CI: 23.0-35; range, 5-68) (total, 1002); of surgeries for biliary malignancies (non-pancreatic), 9.8 (95% CI: 7.3-12.4; range, 2-30); and of main biliary resections for benign conditions, 10.4 (95% CI: 7.6-13.3; range, 2-33). Before surgery, only 41.2% of the sites used nutritional support (&lt; 50% used any nutritional screening procedure). The mean duration of preoperative fasting for solid foods was 9.3 h (range, 6-24 h); it was 6.6 h for liquids (range, 2-12). Following pancreatic surgery, 29.4% tried to use early oral feeding, but 88.2% of the surveyed teams used some nutritional support; 26.5% of respondents used TPN in 100% of cases. Different percentages of TPN and EN were used in the other centers. In malignant biliary surgery, 22.6% used TPN always, and EN in 19.3% of cases. Conclusions: TPN is the commonest nutrition approach after pancreatic head surgery. Only 29.4% of the units used early oral feeding, and 32.3% used EN; 22.6% used TPN regularly after surgery for malignant biliary tumours. The 2006 ESPEN guideline recommendations are not regularly followed 12 years after their publication in our country.Introducción: realizamos una encuesta sobre soporte nutricional perioperatorio en cirugía pancreática y biliar en hospitales españoles en 2007, que mostró que pocos grupos quirúrgicos seguían las guías de ESPEN 2006. Diez años después enviamos un cuestionario para comprobar la situación actual. Métodos: treinta y ocho centros recibieron un cuestionario con 21 preguntas sobre tiempo de ayunas antes y después de la cirugía, cribado nutricional, duración y tipo de soporte nutricional perioperatorio, y número de procedimientos. Resultados: respondieron 34 grupos. La mediana de pancreatectomías (cabeza/total) fue de 29,5 (IC 95 %: 23,0-35; rango, 5-68) (total, 1002), la de cirugías biliares malignas de 9,8 (IC 95 %: 7,3-12,4; rango, 2-30) y la de resecciones biliares por patología benigna de 10,4 (IC 95 %: 7,6-13,3; rango, 2-33). Solo el 41,2 % de los grupos utilizaban soporte nutricional antes de la cirugía (< 50 % habian efectuado un cribado nutricional). El tiempo medio de ayuno preoperatorio para sólidos fue de 9,3 h (rango, 6-24 h), y de 6,6 h para líquidos (rango, 2-12). Tras la pancreatectomía, el 29,4 % habían intentado administrar una dieta oral precoz, pero el 88,2 % de los grupos usaron algún tipo de soporte nutricional y el 26,5 % usaron NP en el 100 % de los casos. Los demás grupos usaron diferentes porcentajes de NP y NE en sus casos. En la cirugía biliar maligna, el 22,6 % utilizaron NP siempre y NE en el 19,3 % de los casos. Conclusiones: la NP es el soporte nutricional más utilizado tras la cirugía de cabeza pancreática. Solo el 29,4 % de las unidades usan nutrición oral precoz y el 32,3 % emplean la NE tras este tipo de cirugía. El 22,6 % de las instituciones usan NP habitualmente tras la cirugía de tumores biliares malignos. Las guías ESPEN 2006 no se siguen de forma habitual en nuestro país tras más de 10 años desde su publicación