Statistical analysis of network traffic for anomaly detection and quality of service provisioning

Network-wide traffic analysis and monitoring in large-scale networks is a challenging and expensive task. In this thesis work we have proposed to analyze the traffic of a large-scale IP network from aggregated traffic measurements, reducing measurement overheads and simplifying implementation issues. We have provided contributions in three different networking fields related to network-wide traffic analysis and monitoring in large-scale IP networks. The first contribution regards Traffic Matrix (TM) modeling and estimation, where we have proposed new statistical models and new estimation methods to analyze the Origin-Destination (OD) flows of a large-scale TM from easily available link traffic measurements. The second contribution regards the detection and localization of volume anomalies in the TM, where we have introduced novel methods with solid optimality properties that outperform current well-known techniques for network-wide anomaly detection proposed so far in the literature. The last contribution regards the optimization of the routing configuration in large-scale IP networks, particularly when the traffic is highly variable and difficult to predict. Using the notions of Robust Routing Optimization we have proposed new approaches for Quality of Service provisioning under highly variable and uncertain traffic scenarios. In order to provide strong evidence on the relevance of our contributions, all the methods proposed in this thesis work were validated using real traffic data from different operational networks. Additionally, their performance was compared against well-known works in each field, showing outperforming results in most cases. Taking together the ensemble of developed TM models, the optimal network-wide anomaly detection and localization methods, and the routing optimization algorithms, this thesis work offers a complete solution for network operators to efficiently monitor large-scale IP networks from aggregated traffic measurements and to provide accurate QoS-based performance, even in the event of volume traffic anomalie

From floodplain to aquatic sediments: Radiogeochronological fingerprints in a sediment core from the mining impacted Sancho Reservoir (SW Spain)

The Sancho Reservoir (SW Spain) was built in 1962, about the time of maximum 137Cs fallout, and it has been affected by acid mine drainage (AMD) particularly since the mining cease in 2001. This is a unique scenario for studying the radiogeochronological fingerprints in AMD-affected sediments deposited over the former flood plain. A sediment core sampled in 2011 was analysed for bulk density, 137Cs, 239Pu, 240Pu, 210Pb, 226Ra, 228Ra, 234Th (238U) and 40K, and studied with various radiometric dating models. Bulk density revealed unsteady compaction and likely depositional events. The activity concentrations of 226Ra, 228Ra, 234Th (238U) and 40K were uniform down-core, but declining overall in the upper 0–25 cm, revealing changes in provenance except for 238U, which increased in the top 10 cm likely due to its supply by AMD. The AMD fingerprint was also found in the 239+240Pu/137Cs activity ratio, which increased in the top sediment layers. The 137Cs and 239+240Pu profiles show well defined peaks at the same depth, with inventories being about four times higher than the expected integrated atmospheric deposition in the area. The unsupported 210Pb (210Pbexc) showed a complex non-monotonic profile interrupted at several sections, particularly around the 137Cs peak. The whole dataset cannot be interpreted in terms of continuous sedimentation processes. Based upon correlated features in the bulk density and 210Pbexc profiles, a series of depositional events (likely linked to peaks in the rainfall records) have been identified in the core. These events date back to the period comprised since the construction of the dam until its increase in height in 1972, which likely displaced upstream the main depositional area of riverine loads, as inferred from sediment trap data. The CRS (with a reference date) and (a piecewise) CIC models have been used for complementing and discussing the chronology.Ministerio de Economia y Competitividad CTM2015-68628-

Connexin 43 plays an important role in the molecular mechanisms implicated in ischemic preconditioning

Comunicaciones a congreso

Assessment oxidative stress biomarkers –neuroprostanes and dihomo-isoprostanes- in elite triathletes urine after two weeks of moderate altitude training

This randomized and controlled trial investigated whether the increase in elite training at different altitudes altered the oxidative stress biomarkers of the nervous system. This is the first study to investigate four F4-neuroprostanes and four F2-dihomo-isoprostanes quantified in 24-hour urine. The quantification was carried out by Ultra High Pressure Liquid Chromatography-triple Quadrupole-Tandem Mass Spectrometry (UHPLC-QqQ-MS/MS). Sixteen elite triathletes agreed to participate in the project. They were randomized in two groups, a group submitted to Altitude Training (n=8) and a group submitted to Sea Level Training (n=8), with a Control group of non-athletes (n=8). After experimental period, the Altitude Training group triathletes gave significant data: 17-epi-17-F2t-dihomo-IsoP (from 5.2 ± 1.4 µg/mL 24 h-1 to 6.6 ± 0.6 µg/mL 24 h-1), ent-7(RS)-7-F2t-dihomo-IsoP (from 6.6 ± 1.7 µg/mL 24 h-1 to 8.6 ± 0.9 µg /mL 24 h-1), and ent-7-epi-7-F2t-dihomo-IsoP (from 8.4 ± 2.2 µg/mL 24 h-1 to 11.3 ± 1.8 µg/mL 24 h-1) increased, while, of the neuronal degeneration-related compounds, only 10-epi-10-F4t-NeuroP (8.4 ± 1.7 µg/mL 24 h-1) and 10-F4t-NeuroP (5.2 ± 2.9 µg/mL 24 h-1) were detected in this group. For the control group and sea level training groups, no significant changes had occurred at the end of the 2-weeks experimental period. Therefore, and as the main conclusion, the training at moderate altitude increased the F4-NeuroPs- and F2-dihomo-isoPs-related oxidative damage of the central nervous system (CNS) compared to similar training at sea level.This study was supported by the project AGL2011-23690 (CICYT) (Spanish Ministry of Economy and Competitiveness). LAGF was granted with a pre-doctoral FPI fellowship BES2012-060185 by the Spanish government. The authors are also grateful to the University of Alicante for its collaboration. Sonia Medina was appointed under a research contract from the project AGL2011-23690 (CICYT)

Monitoring vascular normalization induced by antiangiogenic treatment with (18)F-fluoromisonidazole-PET

This work was supported by the following sources: Fondo de Investigacion Sanitaria (Ministry of Health, Spain; numbers FIS PI10/0288, FIS PI13/00430, FIS PI 11/00616, CPII14/00005 and FIS PI14/00860; the first two awarded to MQF and the last three to MD), and "Fondo Europeo de Desarrollo Regional (FEDER) - Una manera de hacer Europa". MQF is a recipient of a 2010 Beca-Retorno from the AECC Scientific Foundation. Rosae Foundation and AVON Espana S.A.U. contributed to this work with unrestricted donations. Dovitinib was kindly provided by Novartis.BACKGROUND: Rationalization of antiangiogenics requires biomarkers. Vascular re-normalization is one widely accepted mechanism of action for this drug class. The interstitium of tumors with abnormal vasculature is hypoxic. We sought to track vascular normalization with (18)F-misonidazole ([18F]-FMISO, a probe that detects hypoxia) PET, in response to window-of-opportunity (WoO) treatment with the antiangiogenic dovitinib. METHODS: Two patient-derived pancreas xenografts (PDXs; Panc215 and Panc286) and the spontaneous breast cancer model MMTV-PyMT were used. Animals were treated during 1 week of WoO treatment with vehicle or dovitinib, preceded and followed by [18F]-FMISO-PET, [18F]-FDG-PET, and histologic assessment (dextran extravasation, hypoxia and microvessel staining, and necrosis, cleaved caspase-3 and Ki67 measurements). After WoO treatment, gemcitabine (pancreas)/adriamycin (breast) or vehicle was added and animals were treated until the humane endpoint. Tumor growth inhibition (TGI) and survival were the parameters studied. RESULTS: [18F]-FMISO SUV did not change after dovitinib-WoO treatment compared to vehicle-WoO (0.54 vs. 0.6) treatment in Panc215, but it decreased significantly in Panc286 (0.58 vs. 1.18; P < 0.05). In parallel, 10-KDa perivascular dextran extravasation was not reduced with dovitinib or vehicle-WoO treatment in Panc215, but it was reduced in Panc286. Whereas the addition of dovitinib to gemcitabine was indifferent in Panc215, it increased TGI in Panc286 (TGI switched from -59% to +49%). [18F]-FMISO SUV changes were accompanied by an almost 100% increase in interstitial gemcitabine delivery (665-1260 ng/mL). The results were validated in the PyMT model. CONCLUSIONS: [18F]-FMISO accurately monitored vascular re-normalization and improved interstitial chemotherapy delivery.This work was supported by the following sources: Fondo de Investigacion Sanitaria (Ministry of Health, Spain; numbers FIS PI10/0288, FIS PI13/00430, FIS PI 11/00616, CPII14/00005 and FIS PI14/00860; the first two awarded to MQF and the last three to MD), and "Fondo Europeo de Desarrollo Regional (FEDER) - Una manera de hacer Europa". MQF is a recipient of a 2010 Beca-Retorno from the AECC Scientific Foundation. Rosae Foundation and AVON Espana S.A.U. contributed to this work with unrestricted donations. Dovitinib was kindly provided by Novartis.S

Radiation tests on commercial instrumentation amplifiers, analog switches &amp; DAC's

A study of several commercial instrumentation amplifiers (INA110, INA111, INA114, INA116, INA118 & INA121) under neutron and vestigial gamma radiation was done. Some parameters (Gain, input offset voltage, input bias currents) were measured on-line and bandwidth, and slew rate were determined before and after radiation. The results of the testing of some voltage references REF102 and ADR290GR and the DG412 analog switch are shown. Finally, different digital-to-analog converters were tested under radiation

Impact of HLA Mismatching on Early Subclinical Inflammation in Low-Immunological-Risk Kidney Transplant Recipients

The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06-1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04-2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions

Clinical Relevance of Corticosteroid Withdrawal on Graft Histological Lesions in Low-Immunological-Risk Kidney Transplant Patients

The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 +/- 1.2 vs. 5.7 +/- 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 +/- 14.9 vs. 125.7 +/- 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients