Cardiopulmonary bypass down-regulates NOD signaling and inflammatory response in children with congenital heart disease

In the present study, we aimed to examine the impact of cardiopulmonary bypass (CPB) on expression and function of NOD1 and NOD2 in children with congenital heart disease (CHD), in an attempt to clarify whether NOD1 and NOD2 signaling is involved in the modulation of host innate immunity against postoperative infection in pediatric CHD patients. Peripheral blood samples were collected from pediatric CHD patients at five different time points: before CPB, immediately after CPB, and 1, 3, and 7 days after CPB. Real-time PCR, Western blot, and ELISA were performed to measure the expression of NOD1 and NOD2, their downstream signaling pathways, and inflammatory cytokines at various time points. Proinflammatorycytokine IL-6 and TNF-α levels in response to stimulation with either the NOD1 agonist Tri-DAP or the NOD2 agonist MDP were significantly reduced after CPB compared with those before CPB, which is consistent with a suppressed inflammatory response postoperatively. The expression of phosphorylated RIP2 and activation of the downstream signaling pathways NF-κB p65 and MAPK p38 upon Tri-DAP or MDP stimulation in PBMCs were substantially inhibited after CPB. The mRNA level of NOD1 and protein levels of NOD1 and NOD2 were also markedly decreased after CPB. Our results demonstrated that NOD-mediated signaling pathways were substantially inhibited after CPB, which correlates with the suppressed inflammatory response and may account, at least in part, for the increased risk of postoperative infection in pediatric CHD patients.

Linearity analysis and comparison study on the epoc® point-of-care blood analysis system in cardiopulmonary bypass patients

The epoc® blood analysis system (Epocal Inc., Ottawa, Ontario, Canada) is a newly developed in vitro diagnostic hand-held analyzer for testing whole blood samples at point-of-care, which provides blood gas, electrolytes, ionized calcium, glucose, lactate, and hematocrit/calculated hemoglobin rapidly. The analytical performance of the epoc® system was evaluated in a tertiary hospital, see related research article “Analytical evaluation of the epoc® point-of-care blood analysis system in cardiopulmonary bypass patients” [1]. Data presented are the linearity analysis for 9 parameters and the comparison study in 40 cardiopulmonary bypass patients on 3 epoc® meters, Instrumentation Laboratory GEM4000, Abbott iSTAT, Nova CCX, and Roche Accu-Chek Inform II and Performa glucose meters.

Isolation, characterization, and functional assessment of novel smooth muscle like stem progenitors

Vascular smooth muscle cells (VSMC) are one of the key players in the pathogenesis of cardiovascular diseases. The origin of neointimal VSMC has thus become a prime focus of research. VSMC originate from multiple progenitors cell types. In embryo the well-defined sources of VSMC include; neural crest cells, proepicardial cells and EPC. In adults, though progenitor cells from bone marrow (BM), circulation and tissues giving rise to SMC have been identified, no progress has been made in terms of isolating highly proliferative clonal population of adult stem cells with potential to differentiate into SMC. Smooth muscle like stem progenitor cells (SMSPC) were isolated from cardiopulmonary bypass filters of adult patients undergoing CABG. Rat SMSPC have previously been isolated by our group from the bone marrow of Fischer rats and also from the peripheral blood of monocrotaline induced pulmonary hypertension (MCT-PHTN) animal model. Characterization of novel SMSPC exhibited stem cell characteristics and machinery for differentiation into SMC. The expression of Isl-1 on SMSPC provided unique molecular identity to these circulating stem progenitor cells. The functional potential of SMSPC was determined by monitoring adoptive transfer of GFP+ SMSPC in rodent models of vascular injury; carotid injury and MCT-PHTN. The participation of SMSPC in vascular pathology was confirmed by quantifying the peripheral blood, and engrafted levels of SMSPC using RT-PCR. In terms of translating into clinical practice, SMSPC could be a good tool for detecting the atherosclerotic plaque burden. The current study demonstrates the existence of novel adult stem progenitor cells in circulation, with the potential role in vascular pathology.

Profiling side-channel attacks on cryptographic algorithms

Traditionally, attacks on cryptographic algorithms looked for mathematical weaknesses in the underlying structure of a cipher. Side-channel attacks, however, look to extract secret key information based on the leakage from the device on which the cipher is implemented, be it smart-card, microprocessor, dedicated hardware or personal computer. Attacks based on the power consumption, electromagnetic emanations and execution time have all been practically demonstrated on a range of devices to reveal partial secret-key information from which the full key can be reconstructed. The focus of this thesis is power analysis, more specifically a class of attacks known as profiling attacks. These attacks assume a potential attacker has access to, or can control, an identical device to that which is under attack, which allows him to profile the power consumption of operations or data flow during encryption. This assumes a stronger adversary than traditional non-profiling attacks such as differential or correlation power analysis, however the ability to model a device allows templates to be used post-profiling to extract key information from many different target devices using the power consumption of very few encryptions. This allows an adversary to overcome protocols intended to prevent secret key recovery by restricting the number of available traces. In this thesis a detailed investigation of template attacks is conducted, along with how the selection of various attack parameters practically affect the efficiency of the secret key recovery, as well as examining the underlying assumption of profiling attacks in that the power consumption of one device can be used to extract secret keys from another. Trace only attacks, where the corresponding plaintext or ciphertext data is unavailable, are then investigated against both symmetric and asymmetric algorithms with the goal of key recovery from a single trace. This allows an adversary to bypass many of the currently proposed countermeasures, particularly in the asymmetric domain. An investigation into machine-learning methods for side-channel analysis as an alternative to template or stochastic methods is also conducted, with support vector machines, logistic regression and neural networks investigated from a side-channel viewpoint. Both binary and multi-class classification attack scenarios are examined in order to explore the relative strengths of each algorithm. Finally these machine-learning based alternatives are empirically compared with template attacks, with their respective merits examined with regards to attack efficiency.