A Black (and Rising?) Tide: Controlling Maritime Oil Pollution in Canada

A series of dramatic oil spills in recent years has once again drawn critical attention to the nature and adequacy of existing domestic and international legislation regarding ship source oil pollution. Predictably, legislators and policy makers have responded with a plethora of studies, reviews, and consultations. However, past improvements to the domestic and international regimes have traditionally been slow and incremental, at best. In Canada, approximately three years have passed since the Nestucca spill took place off the B.C. coast. Yet, while there has been much discussion, domestic legislation remains virtually unaltered at the present time. The authors find that the status quo must be changed substantially, in order for real and significant improvement in marine environmental protection to be achieved. Mere tinkering with the existing regime has proved to be largely ineffective

Sex, selfish genes, and the shared genome

Sexual conflict can occur whenever the evolutionary interests of males and females differ, and when sexually antagonistic selection acts upon traits shared between the sexes, one or both sexes can be constrained from reaching their phenotypic optima. This intralocus sexual conflict can be characterised by a tug-of-war of allelic replacement until it is resolved, but examples of well-characterised sexually antagonistic loci are rare. This thesis investigates the basis and dynamics of intralocus sexual conflict over insecticide resistance at the Cyp6g1 locus in Drosophila melanogaster, and wing colouration in Drosophila simulans. In D. melanogaster, the Cyp6g1 locus is the site of a series of insecticide resistance alleles, one of which is sexually antagonistic when back-crossed to the old isogenic lab strain Canton-S. I investigated the presence of sexual conflict over this same allele in a recently collected and genetically heterogeneous population. I found evidence of balancing selection on resistance (Ch. 2) that could not be explained by overdominance or sex-specific dominance (Ch. 3). However, balancing selection could be explained by resistance conferring increased fecundity to females (Ch. 2-4), and decreased reproductive success to males (Ch. 4). This male cost can in turn be explained by a negative genetic correlation between reproductive success and Cyp6g1 expression (Ch. 4), possibly influencing levels of reproductive investment (Ch. 2). Additionally, I explored the dynamics of the sex-specific fitness effects of resistance across three Cyp6g1 alleles back-crossed to a single genetic background. I found no evidence of sexual antagonism, but revealed that the cost of resistance increased with more derived alleles, and that all alleles were more costly to females (Ch. 5). After decades of strong selection imposed by insecticide use an unresolved sexual conflict persists at the Cyp6g1 locus despite sexual dimorphism in resistance, and it does not appear that more derived Cyp6g1 alleles are necessarily involved in mediating this conflict. Wing interference patterns (WIPs) are a newly discovered trait subject to female mate choice in Drosophila. I explored the potential for intralocus sexual conflict over WIPs by measuring WIP traits from males and females from populations of D. simulans evolved under relaxed or elevated sexual selection. In response to sexual selection male WIPs evolved to be brighter, higher contrast, and shifted to longer wavelengths of light, but there was no associated response to selection in females (Ch. 6). While WIPs did not appear to be constrained from detectably responding to selection by acute intralocus sexual conflict, male WIPs from the relaxed selection regime were similar to female WIPs, suggesting a cost to sexually selected WIPs that may be indicative of sexually antagonistic selection. IASC is pervasive and can influence a wide range of fundamental evolutionary processes including sexual selection, speciation, and extinction. The research presented in this thesis adds to a body of evidence that sexual dimorphism does not necessarily resolve IASC, and documents the first evidence that WIPs do not appear to be subject to acute IASC and can evolve in response to sexual selection.BBSR

Pediatric Malaria with Respiratory Distress: Prognostic Significance of Point-of-Care Lactate

Respiratory distress (RD) in pediatric malaria portends a grave prognosis. Lactic acidosis is a biomarker of severe disease. We investigated whether lactate, measured at admission using a handheld device among children hospitalized with malaria and RD, was predictive of subsequent mortality. We performed a pooled analysis of Ugandan children under five years of age hospitalized with malaria and RD from three past studies. In total, 1324 children with malaria and RD (median age 1.4 years, 46% female) from 21 health facilities were included. Median lactate level at admission was 4.6 mmol/L (IQR 2.6–8.5) and 586 patients (44%) had hyperlactatemia (lactate \u3e 5 mmol/L). The mortality was 84/1324 (6.3%). In a mixed-effects Cox proportional hazard model adjusting for age, sex, clinical severity score (fixed effects), study, and site (random effects), hyperlactatemia was associated with a 3-fold increased hazard of death (aHR 3.0, 95%CI 1.8–5.3, p \u3c 0.0001). Delayed capillary refill time (τ = 0.14, p \u3c 0.0001), hypotension (τ = −0.10, p = 0.00049), anemia (τ = −0.25, p \u3c 0.0001), low tissue oxygen delivery (τ = −0.19, p \u3c 0.0001), high parasite density (τ = 0.10, p \u3c 0.0001), and acute kidney injury (p = 0.00047) were associated with higher lactate levels. In children with malaria and RD, bedside lactate may be a useful triage tool, predictive of mortality

Validation of two multiplex platforms to quantify circulating markers of inflammation and endothelial injury in severe infection

Biomarkers can prognosticate outcome and enable risk-stratification. In severe infection, focusing on multiple markers reflecting pathophysiological mechanisms of organ injury could enhance management and pathway-directed therapeutics. Limited data exist on the performance of multiplex biomarker platforms. Our goal was to compare endothelial and immune activation biomarkers in severe pediatric infections using two multiplex platforms. Frozen plasma from 410 children presenting to the Jinja Regional Hospital in Uganda with suspected infection was used to measure biomarkers of endothelial (Angiopoietin-2, sFlt-1, sVCAM-1, sICAM-1) and immune (IL-6, IP-10, sTNFR-1, CHI3L1) activation. Two multiplex platforms (Luminex®, EllaTM) based on monoclonal antibody sandwich immunoassays using biotin-streptavidin conjugate chemistry were selected with reagents from R&D Systems. The two platforms differed in ease and time of completion, number of samples per assay, and dynamic concentration range. Intra-assay variability assessed using a coefficient of variation (CV%) was 2.2-3.4 for Luminex® and 1.2-2.9 for EllaTM. Correlations for biomarker concentrations within dynamic range of both platforms were best for IL-6 (ρ = 0.96, p<0.0001), IP-10 (ρ = 0.94, p<0.0001) and sFlt-1 (ρ = 0.94, p<0.0001). Agreement between concentrations obtained by both methods assessed by the Bland-Altman test varied, with best agreement for CHI3L1. Our data suggest that biomarkers of endothelial and immune activation can be readily measured with multiplex platforms. Luminex® and EllaTM produced reliable results with excellent CV% values. The EllaTM platform was more automated and completed in 75 minutes, potentially compatible with near-patient use. Trends in concentrations obtained by these methods were highly correlated, although absolute values varied, suggesting caution is required when comparing data from different multiplex platforms

Fas (CD95) induces rapid, TLR4/IRAK4-dependent release of pro-inflammatory HMGB1 from macrophages

Although Fas (CD95) is recognized as a death receptor that induces apoptosis, recent studies indicate that the Fas/FasL system can induce pro-inflammatory cytokine production by macrophages independent of conventional caspase-mediated apoptotic signaling. The precise mechanism(s) by which Fas activates macrophage inflammation is unknown. We hypothesized that Fas stimulates rapid release of high mobility group box 1 (HMGB1) that acts in an autocrine and/or paracrine manner to stimulate pro-inflammatory cytokine production via a Toll-like receptor-4 (TLR4)/Interleukin-1 receptor associated kinase-4 (IRAK4)-dependent mechanism. Following Fas activation, HMGB1 was released within 1 hr from viable RAW267.4 cells and primary murine peritoneal macrophages. HMGB1 release was more rapid following Fas activation compared to LPS stimulation. Neutralization of HMGB1 with an inhibitory anti-HMGB1 monoclonal antibody strongly inhibited Fas-induced production of tumor necrosis factor (TNF) and macrophage inflammatory protein-2 (MIP-2). Both Fas-induced HMGB1 release and associated pro-inflammatory cytokine production were significantly decreased from Tlr4-/- and Irak4-/- macrophages, but not Tlr2-/- macrophages. These findings reveal a novel mechanism underlying Fas-mediated pro-inflammatory physiological responses in macrophages. We conclude that Fas activation induces rapid, TLR4/IRAK4-dependent release of HMGB1 that contributes to Fas-mediated pro-inflammatory cytokine production by viable macrophages

Modeling, Reduction, and Control of a Helically Actuated Inertial Soft Robotic Arm via the Koopman Operator

Soft robots promise improved safety and capability over rigid robots when deployed in complex, delicate, and dynamic environments. However, the infinite degrees of freedom and highly nonlinear dynamics of these systems severely complicate their modeling and control. As a step toward addressing this open challenge, we apply the data-driven, Hankel Dynamic Mode Decomposition (HDMD) with time delay observables to the model identification of a highly inertial, helical soft robotic arm with a high number of underactuated degrees of freedom. The resulting model is linear and hence amenable to control via a Linear Quadratic Regulator (LQR). Using our test bed device, a dynamic, lightweight pneumatic fabric arm with an inertial mass at the tip, we show that the combination of HDMD and LQR allows us to command our robot to achieve arbitrary poses using only open loop control. We further show that Koopman spectral analysis gives us a dimensionally reduced basis of modes which decreases computational complexity without sacrificing predictive power.Comment: Submitted to IEEE International Conference on Robotics and Automation, 202

Accidental Drop of a Carbon Steel/Lead Shipping Cask (HFEF 14) at Low Temperatures

A shielded cask is used to transport radioactive materials between facilities at the Idaho National Laboratory. The cask was fabricated with an outer and inner shell of A36 carbon steel with lead poured in the annular space between the shells to provide radiation shielding. Carbon steel is known to be susceptible to low-temperature brittle fracture under impact loading. This paper will present the analysis results representing postulated transportation accidents during on-site transfers of the cask at subzero temperatures. The accident scenarios were based on a series of cask drops onto a rigid surface from a height of 1.83m (6 ft.) Finite element models of the cask and its contents were solved and post processed using the ABAQUS software. Each model was examined for failure to contain radioactive materials and/or significant loss of radiation shielding. Results of these analyses show that the body of the cask exhibits considerable ruggedness and will remain largely intact after the impact. There will be deformation of the main cask body with localized brittle failure of the cask outer shell and door structure. The cask payload outer waste can remains in the cask but will experience some permanent plastic deformation in each drop. It will not be deformed to the point where it will rupture, thus maintaining confinement of the can contents

On Corrective Patterns for the SHA-2 Family

The Secure Hash Standard (SHS) [3] includes hashing algorithms denoted SHA-n, (n in {224, 256, 384, 512}) for producing message digests of length n. These algorithms are based on a common design, sometimes known as SHA-2, that consists of a message schedule and a register. The most successful attacks on the SHA algorithms are Chabaud-Joux differential collisions [1, 2, 4, 5, 7], which are based on finding a corrective pattern for the register. Previous analysis of the SHA-2 algoritms [4] indicated that, for all SHA-2 algorithms, the best corrective pattern has probability 2^-66. We find that the complexity of obtaining a collision is 2^39 when the register state is unknown. Of this complexity, a factor of 2^9 corresponds to conditions on the internal state that must be satisfied, and a factor of 2^30 corresponds to 30 bits of internal state that must be guessed correctly in order to generate a collision. When the register state is known (as is the case when generating a hash) then the guessed bits are known and the complexity is reduced to 2^9. The simple analysis of the message schedule in [4] determines limits on the probability of collision for SHA-2, and was sufficient at that time to conclude that the algorithms resist the attacks. In [4] the claimed complexity is compared against the birthday attack bound of 2^n/2. However, the corrective pattern can be converted into a second pre-image attack for which the complexity should be greater than 2^n. When accounting for the complexity of 2^9 per corrective pattern, the previous analysis of the message schedule yields lower bounds on the complexities 2^27 for SHA-224/256 and 2^45 for SHA-224/256. These complexities are significantly less than the 2^n bound. It is no longer certain that SHA-2 resists this attack. More detailed analysis of the message schedule is required

The Mundja Streaming MAC

Mundja is a MAC generation algorithm that has been designed for use together with a stream cipher. Mundja accumulates the message onto two independent registers: the first is a Cyclic Redundancy Checksum (CRC) that uses linear feedback; the second is a strengthened version of the SHA-256 register that uses nonlinear feedback. Mundja is fast (asymptotically about 4 times the speed of HMAC-SHA-256), and can generate MACs of any desired length. Mundja is designed to be secure at the equivalent level of 128-bit keys. When used in cooperation with a correspondingly secure stream cipher, it is hoped to remain secure even at the equivalent level of 256-bit keys. Appendices give details of the use of Mundja with the SOBER-128, Turing and RC4 stream ciphers