Influence of hCG on inducible nitric oxide synthase gene expression in ram testicular arteries

Background. Experimental evidence suggests a relationship between the vasodilatory effect of hCG and the NOS system in the testis. The influence of hCG administration on testicular vascular NOS gene expression has not been fully investigated. Objective: This study aimed to evaluate the presence of the nitric oxide syntheses gene in ram testicular arteries and the influence of hCG administration on its expression. Materials and methods: Both testicular arteries of sixteen rams were extracted before and after i.v. administration of 5000 IU of hCG or placebo. The expression of the iNOS gene was investigated by real time PCR. Data were analyzed by means of Wilcoxon and Mann-Whitney tests. A p value of < 0.05 was considered statistically significant. Results: PCR revealed the presence of iNOS mRNA in all basal samples but the expression of the iNOS gene was significantly reduced in all arteries obtained 24 h after the administration of either hCG or placebo. A significant reduction in the expression of iNOS gene was observed in the testicular arteries extracted after 24 h in both treated and placebo groups. On the other hand hCG stimulation did not significantly influence iNOS expression following its administration compared to a placebo. Conclusion: Ram testicular arteries express the iNOS gene but hCG stimulation did not significantly influence iNOS expression. A significant reduction in the expression of this gene was observed in the testicular arteries extracted after 24 h in both treated and placebo groups, suggesting that iNOS expression on the testicular artery could be influenced by the spermatic vessel ligation of the controlateral testis

The use of autologous platelet rich plasma gel in bulbar and penile buccal mucosa urethroplasty: Preliminary report of our first series

Objective: The Buccal Mucosa (BM) UrethroPlasty (UP) is one of the preferred treatments for long or compli-cated urethral strictures. We propose the use of autologous Platelet Rich Plasma gel (aPRPg) in order to enhance to vascularization of BM graft and reduce the fibrous spongy. We report the outcome of our ten cases of bulbar and penile UP and the safety of this technique. Materials and metods: Ten patients underwent to BM UP with use of aPRP gel. Median age was 46. Stricture etiology was idiopathic, failed hypospadias and flogistic. Average stricture length was 3.7 cm. All patient were preoperatively evaluated with uroflowmetry , retrograde urethrography, cystoscopy and questionnaire. The harvesting of the aPRP was performed in blood bank from peripheral venous sample. Catheter was usually removed after 3 weeks and urethrography was performed after 6 weeks. Results: All patients reported no problem on the donor site. At time of follow-up (median 20 month, 12-34) all patients refer no problem and a good uroflowmetry. No re-strictures at the anastomotic sites were demonstrated in any of the patients. Conclusion: However in our experience the follow-up is limited and no definitive conclusion or comparison can be made with the original BM UP. The use of aPRP gel seems feasible and safe. In our opinion it is important to continue investigating this procedure for its advantages in case of complex urethral strictures complicated by fibrous spongy, above all in penile urethral strictures post hypospadia repair

Robot-assisted excision of seminal vesicle cyst associated with ipsilateral renal agenesis

Seminal vesicle cysts (SVCs) associated with other genitourologic abnormalities are rare. Often associated with ipsilateral renal agenesis in a symptomatic patient. In symptomatic patients open surgical excision is the treatment of choice. The laparoscopic approach is a less invasive option. Recently robot-assisted management has gained a primary role for the treatment of this condition

The RECIPE approach to challenges in deeply heterogeneous high performance systems

[EN] RECIPE (REliable power and time-ConstraInts-aware Predictive management of heterogeneous Exascale systems) is a recently started project funded within the H2020 FETHPC programme, which is expressly targeted at exploring new High-Performance Computing (HPC) technologies. RECIPE aims at introducing a hierarchical runtime resource management infrastructure to optimize energy efficiency and minimize the occurrence of thermal hotspots, while enforcing the time constraints imposed by the applications and ensuring reliability for both time-critical and throughput-oriented computation that run on deeply heterogeneous accelerator-based systems. This paper presents a detailed overview of RECIPE, identifying the fundamental challenges as well as the key innovations addressed by the project. In particular, the need for predictive reliability approaches to maximizing hardware lifetime and guarantee application performance is identified as the key concern for RECIPE. We address it through hierarchical resource management of the heterogeneous architectural components of the system, driven by estimates of the application latency and hardware reliability obtained respectively through timing analysis and modeling thermal properties and mean-time-to-failure of subsystems. We show the impact of prediction accuracy on the overheads imposed by the checkpointing policy, as well as a possible application to a weather forecasting use case.The activities described in this article received funding from the European Union's Horizon 2020 research and innovation programme under the FETHPC grant agreement no. 801137 RECIPE: REliable power and time-ConstraInts-aware Predictive management of heterogeneous Exascale systems.Agosta, G.; Fornaciari, W.; Atienza, D.; Canal, R.; Cilardo, A.; Flich Cardo, J.; Hernández Luz, C.... (2020). The RECIPE approach to challenges in deeply heterogeneous high performance systems. Microprocessors and Microsystems. 77:1-13. https://doi.org/10.1016/j.micpro.2020.103185S11377Flich, J., Agosta, G., Ampletzer, P., Alonso, D. A., Brandolese, C., Cappe, E., … Zoni, D. (2018). Exploring manycore architectures for next-generation HPC systems through the MANGO approach. Microprocessors and Microsystems, 61, 154-170. doi:10.1016/j.micpro.2018.05.011https://euroexa.eu.https://www.altera.com/products/sip/memory/stratix-10-mx/overview.html.http://www.mango-project.eu.https://www.infinibandta.org/infiniband-roadmap/.Reghenzani, F., Massari, G., & Fornaciari, W. (2018). chronovise: Measurement-Based Probabilistic Timing Analysis framework. Journal of Open Source Software, 3(28), 711. doi:10.21105/joss.00711Abella, J., Padilla, M., Castillo, J. D., & Cazorla, F. J. (2017). Measurement-Based Worst-Case Execution Time Estimation Using the Coefficient of Variation. ACM Transactions on Design Automation of Electronic Systems, 22(4), 1-29. doi:10.1145/3065924https://lanl.gov/projects/trinity/specifications.php.https://www.bsc.es/marenostrum/marenostrum/technical-information.https://www.olcf.ornl.gov/olcf-resources/compute-systems/titan/.Bellasi, P., Massari, G., & Fornaciari, W. (2015). Effective Runtime Resource Management Using Linux Control Groups with the BarbequeRTRM Framework. ACM Transactions on Embedded Computing Systems, 14(2), 1-17. doi:10.1145/2658990Egwutuoha, I. P., Levy, D., Selic, B., & Chen, S. (2013). A survey of fault tolerance mechanisms and checkpoint/restart implementations for high performance computing systems. The Journal of Supercomputing, 65(3), 1302-1326. doi:10.1007/s11227-013-0884-0Lee, K., & Wong, S. S. (2017). Fault-Tolerant FPGA with Column-Based Redundancy and Power Gating Using RRAM. IEEE Transactions on Computers, 66(6), 946-956. doi:10.1109/tc.2016.2634533Cheatham, J. A., Emmert, J. M., & Baumgart, S. (2006). A survey of fault tolerant methodologies for FPGAs. ACM Transactions on Design Automation of Electronic Systems, 11(2), 501-533. doi:10.1145/1142155.1142167Parris, M. G., Sharma, C. A., & Demara, R. F. (2011). Progress in autonomous fault recovery of field programmable gate arrays. ACM Computing Surveys, 43(4), 1-30. doi:10.1145/1978802.1978810A. Iranfar, F. Terraneo, W.A. Simon, L. Dragic, I. Pilji, M. Zapater Sancho, W. Fornaciari, M. Kovac, D. Atienza Alonso, Thermal characterization of next-generation workloads on heterogeneous MPSoCs (2017).Zoni, D., & Fornaciari, W. (2015). Modeling DVFS and Power-Gating Actuators for Cycle-Accurate NoC-Based Simulators. ACM Journal on Emerging Technologies in Computing Systems, 12(3), 1-24. doi:10.1145/2751561Curtsinger, C., & Berger, E. D. (2013). STABILIZER. ACM SIGARCH Computer Architecture News, 41(1), 219-228. doi:10.1145/2490301.2451141Kormann, J., Rodríguez, J. E., Gutierrez, N., Ferrer, M., Rojas, O., de la Puente, J., … Cela, J. M. (2016). Toward an automatic full-wave inversion: Synthetic study cases. The Leading Edge, 35(12), 1047-1052. doi:10.1190/tle35121047.1Fusi, M., Mazzocchetti, F., Farres, A., Kosmidis, L., Canal, R., Cazorla, F. J., & Abella, J. (2020). On the Use of Probabilistic Worst-Case Execution Time Estimation for Parallel Applications in High Performance Systems. Mathematics, 8(3), 314. doi:10.3390/math8030314D.W. Wright, R.A. Richardson, W. Edeling, J. Lakhlili, R.C. Sinclair, V. Jacauskas, D. Suleimenova, B. Bosak, M. Kulczewski, T. Piontek, P. Kopta, I. Chirca, H. Arabnejad, O.O. Luk, O. Hoenen, J. Weglarz, D. Crommelin, D. Groen, Building confidence in simulation: Application of easyvvuq, Submitted to Journal of Advanced Theory and Simulations on 12/12/2019

Challenges in Deeply Heterogeneous High Performance Systems

RECIPE (REliable power and time-ConstraIntsaware Predictive management of heterogeneous Exascale systems) is a recently started project funded within the H2020 FETHPC programme, which is expressly targeted at exploring new High-Performance Computing (HPC) technologies. RECIPE aims at introducing a hierarchical runtime resource management infrastructure to optimize energy efficiency and minimize the occurrence of thermal hotspots, while enforcing the time constraints imposed by the applications and ensuring reliability for both time-critical and throughput-oriented computation that run on deeply heterogeneous acceleratorbased systems. This paper presents a detailed overview of RECIPE, identifying the fundamental challenges as well as the key innovations addressed by the project, which span run-time management, heterogeneous computing architectures, HPC memory/interconnection infrastructures, thermal modelling, reliability, programming models, and timing analysis. For each of these areas, the paper describes the relevant state of the art as well as the specific actions that the project will take to effectively address the identified technological challenge

Challenges in deeply heterogeneous high performance systems

© 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes,creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.RECIPE (REliable power and time-ConstraInts-aware Predictive management of heterogeneous Exascale systems) is a recently started project funded within the H2020 FETHPC programme, which is expressly targeted at exploring new High-Performance Computing (HPC) technologies. RECIPE aims at introducing a hierarchical runtime resource management infrastructure to optimize energy efficiency and minimize the occurrence of thermal hotspots, while enforcing the time constraints imposed by the applications and ensuring reliability for both time-critical and throughput-oriented computation that run on deeply heterogeneous accelerator-based systems. This paper presents a detailed overview of RECIPE, identifying the fundamental challenges as well as the key innovations addressed by the project, which span run-time management, heterogeneous computing architectures, HPC memory/interconnection infrastructures, thermal modelling, reliability, programming models, and timing analysis. For each of these areas, the paper describes the relevant state of the art as well as the specific actions that the project will take to effectively address the identified technological challenges.Peer Reviewe

Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia

Gamma-secretase inhibitors (GSIs) block the activation of the oncogenic protein Notch homolog-1 (NOTCH1) in T cell acute lymphoblastic leukemia (T-ALL). However, limited antileukemic cytotoxicity and severe gastrointestinal toxicity have restricted the clinical application of these targeted drugs. Here we show that combination therapy with GSIs plus glucocorticoids can improve the antileukemic effects of GSIs and reduce their gut toxicity in vivo. Inhibition of NOTCH1 signaling in glucocorticoid-resistant T-ALL restored glucocorticoid receptor autoupregulation and induced apoptotic cell death through induction of the gene encoding BCL-2-like apoptosis initiator-11 (BCL2L11). GSI treatment resulted in cell cycle arrest and accumulation of goblet cells in the gut mediated by upregulation of the gene encoding the transcription factor Kruppel-like factor-4 (Klf4), a negative regulator of the cell cycle required for goblet cell differentiation. In contrast, glucocorticoid treatment induced transcriptional upregulation of cyclin D2 (Ccnd2) and protected mice from developing the intestinal goblet cell metaplasia typically induced by inhibition of NOTCH signaling with GSIs. These results support a role for glucocorticoids plus GSIs in the treatment of glucocorticoid-resistant T-ALL