Thermal scavenging is a unique behavior restricted to a few desert ant genera. Workers are among the most thermotolerant land animals known to this day, being able to survive body temperatures of sometimes more than 50°C for several minutes. Making use of their remarkable heat-hardiness, they search for food in plain day, a feat that other desert creatures cannot accomplish. They mostly feed on the corpses of heat-stricken, less tolerant arthropods that were unable to survive the blazing sun of the midday desert. Thermal scavenging has evolved independently at least three times in distantly related genera, geographical well segregated inside the different deserts of the world. First, the Cataglyphis genus ranges from the Sahara Desert and extends its distribution to reach minor Asia through the Mediterranean Basin. Second the Ocymyrmex genus can be found in the Namib and Karoo deserts of southern Africa, extending its range to eastern Africa savanna plains. Finally, the Melophorus genus can be found in Australia, with thermal scavenging species distributed in the central desert of the outback region.While this impressive behavior was already well-described by the start of this PhD project, little was known about the mechanisms supporting the remarkable heat-tolerance of workers. Using biophysical and physiological approaches in Cataglyphis and Ocymyrmex, we’ve been able to pinpoint key aspects underlying stress tolerance in those genera. First, from a biophysical standpoint, the Sahara silver ant Cataglyphis bombycina is covered with a unique and dense array of prismatic hairs reflecting visible wavelengths by total internal reflection. This allows reflection of up to 50% of the incident sunlight energy, thus shifting down the ant’s thermal equilibrium and sparing its body a few critical degrees. Second, in a comparative framework, we found numerous genes involved with critical cellular processes to be constitutively expressed or strongly up-regulated to heat in thermal scavenging ants, while their orthologs were not in mesophilic species. Those processes, such as molecular chaperoning, cell-cycle regulation, energy metabolism and muscular functions are keys that allow those ants to meet the higher requirement needed to scavenge for food at both stunning speed and under extreme heat-pressure. Overall, this work investigates the physiological and biophysical basis enabling thermal scavenging ants to survive extreme heat conditions. It provides a deeper understanding of cellular heat-tolerance pathways in non-model animals and contribute to our knowledge of life’s adaptation to extreme conditions. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Shock control bumps (SCBs) are considered promising flow control devices for transonic commercial aircraft. By generating a λ-shock structure, 2D SCBs offer large drag savings, but perform poorly when that structure breaks down off-design. Milder-performing 3D devices produce weak vortices, that may offer some boundary layer control, and SCBs also affect buffet via direct impact on shock motions and separation. To date however, design studies have largely ignored complications from the swept, spanwise-varying flows, so this thesis tackles the question of whether SCB arrays can offer useful benefits to the performance of transonic commercial aircraft. Using a numerical infinite-wing model, a simple rotation adaptation is shown to redress deficient on-design drag performance of 3D SCBs under swept flows. With the correct rotation (dependent on height, planform and spacing) bumps follow performance-design trends similar to those in unswept flow. With this knowledge, an array design method is developed to tailor 2D and 3D devices to local flow conditions on an aircraft model, aiming to maximise on-design drag performance. Careful infinite-wing setup means the influence of rotation and array height on performance is replicated on the aircraft. Predicted array designs achieve 74-87% of their estimated local drag savings. However, with wave drag being a smaller percentage of the total, the influence of arrays on lift is more significant and makes the optimal designs shorter than predicted. Strategies for improving off-design drag performance are then evaluated. Stagger, an alternating chordwise translation applied to 3D arrays, broadens operating range and lowers drag penalties by better accommodating off-design shock movements, but offers a less favourable trade-off against on-design drag than simply reducing the array height. However, a 2D array can always outperform a 3D on drag objectives. Lastly, buffet performance is inferred using steady indicators based on trailing edge pressure and shock location. These disagree regarding the impact on buffet onset, unresolvably due to a lack of validation data, but agree that arrays could alleviate flow development post-onset. Optimal array designs depend on prioritised objectives: considering buffet severity and on-design drag, tall 2D (or 3D) arrays; for buffet and minimum off-design drag penalties (similar to the motivation behind vortex generator application), 3D arrays of varying height and stagger. A simple flight fuel consumption model utilising the computed drag data shows that many arrays are neutral or offer small savings (up to 0.3%) across a range of mission profiles. While likely too small to merit application for solely drag purposes, this implies buffet benefits without cost to efficiency. Unsteady tests and proper assessment of buffet onset are needed to confirm this.

Sepsis has been defined as a systemic response to an infection. With an incidence of 3 per 1000 population per year or about 750 000 cases a year, this syndrome ranks as the 10th leading cause of death in the United States (1). Increasing severity of sepsis correlates with increasing mortality, which rises from 30-40% for severe sepsis up to 40-60% for septic shock. This thesis examines the effectiveness of adjunctive therapies, including activated protein C, hypercapnia and acidosis, and sodium selenite, in a clinically relevant ovine model of septic shock. The results from these studies can provide valuable information for future clinical trials on sepsis.<p>This thesis is divided into four sections: 1) sepsis overview; 2) an autologous fecal peritonitis model in sheep and its evaluation; 3) the series of studies on adjunctive therapeutics; and 4) ongoing studies and future perspective.<p>In the first section, a broad overview gives a rough introduction to delineate many aspects of sepsis syndrome such as terminology, etiology, epidemiology, pathophysiology and current guidelines for management. Hemodynamics in sepsis are especially elaborated since these are major observations throughout the studies presented later.<p>In the second section, the general characteristics of the sepsis models used in this thesis are elucidated. Data on hemodynamics, lung mechanics, gas exchange, etc. are presented to feature the ovine peritonitis model. The results of laboratory examinations for hematology, coagulation, bacteriology, biochemistry and hormonology are also presented. And then, I review currently used sepsis models with regards to their advantages and disadvantages.<p>The third section discusses three studies with their objectives, the methods used, the major findings, and the potential clinical implications.<p>9<p>1) Beneficial effects of recombinant human activated protein C in experimental septic shock. Activated protein C has a multitude of beneficial effects in severe sepsis and septic shock, including anti-inflammation, anti-coagulation, profibrinolysis, anti-apoptosis and endothelial protection. A clinical Phase III trial demonstrated that the administration of recombinant human activated protein C improved survival in patients with severe sepsis. However, doubts on the protective effects of activated protein C have persisted and been refueled by the recently published negative trials in less severely ill patients and in children. In the light of these ambiguities and uncertainties, we reinvestigated the effects of activated protein C in experimental septic shock.<p>2) Acute hypercapnia improves indices of tissue oxygenation more than dobutamine in septic shock. Hepercapnia has been found to possess beneficial effects in diverse acute inflammatory states independent of protective lung mechanics. To prove the hypothesis that acute hypercapnia has similar or superior hemodynamic effects to those of a dobutamine infusion, which may be particularly relevant in the presence of hemodynamic instability associated with respiratory failure, we investigated the effects of hypercapnia, which induced by inspiring extrinsic carbon dioxide in experimental septic shock.<p>3) High bolus dose of sodium selenite prolongs survival in an ovine model of septic shock. Selenite has both pro- and anti-oxidant effects. The administration of high dose sodium selenite may improve survival in septic shock patients. The benefit may be greater with the administration of a bolus (to achieve higher concentrations) rather than a continuous infusion. To test this hypothesis, we examined the effects of a high dose bolus administration of sodium selenite in experimental septic shock.<p>The fourth and final section talks about currently ongoing studies and offers some perspective on future direction. / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Stochastic differential equations are becoming a popular tool for modeling the transport and acceleration of cosmic rays in the heliosphere. In diffusive shock acceleration, cosmic rays diffuse across a region of discontinuity where the up- stream diffusion coefficient abruptly changes to the downstream value. Because the method of stochastic integration has not yet been developed to handle these types of discontinuities, I utilize methods and ideas from probability theory to develop a conceptual framework for the treatment of such discontinuities. Using this framework, I then produce some simple numerical algorithms that allow one to incorporate and simulate a variety of discontinuities (or boundary conditions) using stochastic integration. These algorithms were then modified to create a new algorithm which incorporates the discontinuous change in diffusion coefficient found in shock acceleration (known as Skew Brownian Motion). The originality of this algorithm lies in the fact that it is the first of its kind to be statistically exact, so that one obtains accuracy without the use of approximations (other than the machine precision error). I then apply this algorithm to model the problem of diffusive shock acceleration, modifying it to incorporate the additional effect of the discontinuous flow speed profile found at the shock. A steady-state solution is obtained that accurately simulates this phenomenon. This result represents a significant improvement over previous approximation algorithms, and will be useful for the simulation of discontinuous diffusion processes in other fields, such as biology and finance.

In order to survive, cells must be able to cope with a variety of environmental stressors. The heat shock response (HSR) is a pro-survival mechanism employed by cells in response to protein denaturing stress, such as heat. Since its discovery in 1960, the heat shock response has been found to be regulated by the transcription factor heat shock factor 1 (HSF1). During periods of increased stress, HSF1 undergoes a multi-step process of activation that involves homotrimerization, DNA-binding, and post-translational regulatory modifications, all of which ultimately function to control the transcription of chaperone genes. These chaperone genes encode molecular chaperone proteins which function to promote survival during stress by restoring protein homeostasis to the cell. Although HSF1 is classically studied for its role in regulating the HSR, HSF1 also has roles in regulating metabolism, development, and longevity. Studies in the nematode Caenorhabditis elegans demonstrate the HSF1 homolog, HSF-1, as a global regulator of gene expression that has both stress-dependent and -independent functions. Modulating HSF1 activity therefore has implications beyond stress-induced processes, and has been suggested as a promising therapeutic target for diseases of aging and protein dysfunction. We were interested in determining regulators of the HSR using C. elegans as a model to test for effects on proteostasis and longevity. In these studies, we observed the effects of compound treatment (Chapters 1 and 2), genetic manipulation (Chapters 3 and 4), and environmental stimuli (Chapters 5 and 6), on the HSR in C. elegans. In Chapters 1 and 2, we describe our findings that treatment with the DNA synthesis inhibitor Fluorodeoxyuridine, and treatment with coffee and caffeine, enhance the heat shock response and improve proteostasis in aging worms in an HSF-1-dependent manner. In Chapters 3 and 4, we uncovered that negative regulation of the HSR by the cell cycle and apoptosis regulator CCAR2 is conserved in C. elegans, and is mediated by the CCAR2 ortholog, LST-3. We also uncovered that negative regulation of the HSR by LST-3 requires the SIRT1 homolog Sir-2.1, and knockdown of LST-3 via lst-3 RNAi works through Sir-2.1 to enhance stress-resistance, fitness, proteostasis and longevity. In Chapters 5 and 6, we describe the global impact of HSF-1 in regulating transcriptional processes during a heat stress. The profiling of global HSF-1 mRNA and miRNA targets has allowed us to uncover a heat-dependent and -independent role for HSF-1 in regulating gene expression to impact stress-resistance, proteostasis, and longevity. Altogether, these studies demonstrate the impact of compound treatment, genetic manipulation, and environmental stimuli on the heat shock response, while also uncovering global stress-dependent and -independent roles for HSF-1. This work therefore provides insight into various methods of activating the HSR by modulating HSF-1 activity, and uncovering global HSF-1 target genes, which may be useful for designing therapeutic treatment strategies for diseases of protein dysfunction.

The current study addresses the stability of shock waves propagating through dissipative media, analogous to both granular media and molecular gases undergoing endothermic reactions. In order to investigate the stability, a simple molecular dynamics model was developed to observe shock waves and their structures with the inclusion of energy dissipation. For this, an Event Driven Molecular Dynamics model was implemented in a 2D environment, where a molecule is represented by a disk. The simulations addressed the formation of a shock wave in a gas by the sudden acceleration of a piston. Inelastic collisions were assumed to occur only if an impact velocity threshold is surpassed, representing the activation energy of the dissipative reactions. Parametric studies were conducted for this molecular model, by varying the strength of the shock wave, the activation threshold and the degree of inelasticity in the collisions. The resulting simulations showed that a shock structure does indeed become unstable with the presence of dissipative collisions. This instability manifests itself in the form of distinctive high density non-uniformities behind the shock wave, which take the form of convective rolls. The spacing and size of this ``finger-like" unstable pattern was shown to be dependent on the degree of inelasticity, the activation energy, and the strength of the driving piston. The mechanism responsible for the instability was addressed by studying the time evolution of the material undergoing the shock wave compression and further relaxation. It is found that the gas develops the instability on the same time scales as the clustering instability in homogeneous gases, first observed by Goldhirsch and Zanetti in granular gases. This confirmed that the clustering instability is the dominant mechanism.

The aim of this thesis is the innovation of the testing device which is located in Institute of Machine and Industrial Design laboratory. The innovation relates to the portal construction design, where will be placed the hydraulic pulsator from the company INOVA Praha Ltd. New portal construction will be designed with respect to specified parameters and requirements and also with regard to the performed tests (damper tests, vibroizolated properties magnetorheological valves tests etc.). The thesis contains detailed analysis of the current tester and detailed analysis of similar machines with focusing on the portal structure and ways of positioning the crossmember. Further parts of the thesis is a detailed description of the design solution, including the computational simulations, attached drawing documentation and experimentally verified functional sample (crossmember).

Shockvertising is a set of advertising tactics that sends its message through the breaking of norms, presentation of shocking images, exploiting the audience’s anxieties, and various other ways. It is a quick way to break through the clutter of similar advertisements in today’s oversaturated world of advertising. While shockvertising is a relatively common tactic in the non-profit sector, this thesis focuses on its use in the for-profit sector and the specific pitfalls and benefits it faces in this context. The focus here is on advertisers, as those who are sending the message, rather than on the receivers. This is done to build a sturdy theoretical base for anyone interested in using or studying shock in their advertising.    The core of the study shows factors influencing the conception and subsequent creation of a shocking ad while also connecting it to the effect it has on the audience. Through interviewing professionals in the field and connecting their experience to previous studies, the AMEE model is created to facilitate an easier and safer way of using shock in advertising. This model and its thorough explanation can also be found separately in the appendices.   Many important factors that influence the success and effectiveness of a shocking ad have been discovered, analysed, and presented in this study. The findings show that the most important factors are a relevant and purposeful Source of Shock, alignment with the Brand Image, the understanding of the Receiver, and the Context in which a shocking ad appears.

To break through the clutter of advertisements, some advertisers uses sexual appeal as a technique to increase visibility and sales. The purpose of this study is to examine, from a Swedish and South Korean perspective, how the attitude towards sexual appeal in advertising differ between generations. Culture and age has been proven to be factors affecting attitude towards advertisements, and previous research has found that the attitude towards sexual appeal in advertising between Swedish and South Korean university students only differed slightly. To examine the attitudes, data was collected through a questionnaire. The results suggest that the attitudes of each age group are generally rather similar, regardless of culture. Ages 18 to 30 showed most negativity towards sexual appeal in advertisements.

Introduction: Myocardial Infarction (MI) is the leading cause of premature death worldwide. During MI-induced ischemia, the release of heat shock proteins (HSPs), a classic damage-associated molecular pattern (DAMP), by severely injured cells leads to prolonged inflammation through their activation of innate pattern recognition receptors, fibrosis, and subsequent contractile dysfunction. The regulation of HSPs is orchestrated by its master transcription factor, Heat Shock Factor 1 (HSF1). However, it is unknown if HSF1 is a potential integrated functional target to improve MI outcomes. We addressed this question by asking if the coordinated modulation of HSPs via genetic deletion of Hsf1 can be beneficial in MI. Hypothesis: We hypothesized that genetic deletion of Hsf1 can lead to improved survival and left ventricle (LV) remodeling through reduction of pro-inflammatory pathway activation in a murine model of MI-induced coronary artery ligation. Methods and Results: Eleven to thirteen-week-old male Hsf1-/- mice and Hsf1+/+ littermate controls were subjected to MI by left anterior descending (LAD) coronary artery ligation or sham operation. Hsf1-/- mice subjected to induced-MI had a significant higher survival rate (74%) at 28 days than WT mice post-MI in the same time frame (34%, p<0.001). Echocardiography at 3, 7, and 28 days post-MI; however, did not identify any difference in LV function between Hsf1+/+ and Hsf1-/- mice. Masson Trichrome and Picro Sirius Red staining of heart tissue sections following 7 days of sham or MI-operation indicated that MI-operated Hsf1-/- hearts had a significant smaller infarct size than Hsf1+/+ hearts at 19% compared to 32% (p<0.05), respectively; and less collagen deposition when compared to WT littermates. Cardiac expression of heat shock proteins was significantly lowered in the Hsf1-/- hearts compared to Hsf1+/+ hearts following 3 and 7 days of MI. However, no significant difference was observed in number of immune cells, cardiac gene expression of pro-inflammatory cytokines and chemokines, cardiac protein expression of NF-κB and MAPK-ERK1/2 signaling proteins, and serum IL-6 concentration between Hsf1+/+ and Hsf1-/- mice 3 days post-MI. Following 7 days of MI, there is a significant increase in the gene expression of pro-inflammatory cytokines, such as Il1b, and chemokines, such as Ccl2, in Hsf1-/- hearts than Hsf1+/+ hearts. Conclusion & Future Directions: Overall, the loss of Hsf1 improved survival and reduced infarct size following MI. However, its deletion did not affect inflammatory processes until 7 days post-MI or improved cardiac function in our specific murine MI model.