Steer calves n = 345 (year 1 n = 183; 253 ± 35 kg, year 2 n = 162; 241 ± 36 kg initial BW) were used to evaluate 56-d preconditioning systems in each of two years. Angus- and Charolais-sired calves out of crossbred dams were assigned to systems within breed and BW strata. The systems consisted of ad libitum access to a self-fed milo-based diet in drylot (DL); ad libitum access to the same self-fed diet while grazing dormant warm season pasture (SF); and hand-fed 20 precent CP pellets (2.1 kg 3 times/wk; equivalent to 0.89 kg/steer per d) while grazing dormant warm season pasture (HF). Steers were weighed after overnight shrink on d 0, 28, and 56. The economic analysis was based on current local prices for cattle and inputs. Morbidity and mortality rates were similar among treatments. In year 1, one steer was removed from SF (mechanical) and one from DL (chronic bloat). In year 2, two steers were treated for respiratory disease (DL and HF) and mortalities occurred in DL (1 steer, digestive), HF (1 steer, unknown) and SF (1 steer, mechanical). Shrink from weaning to d 0 averaged 4.45 percent across years and was similar (P = 0.70) among treatments. Across years, ADG was lower in HF vs. SF or DL-fed steers (P < 0.01), which had similar rates of gain (P = 0.29; 0.13, 0.98, and 0.96 ± 0.03 kg/d yr 1; P = 0.13; 0.14, 0.73, 0.79 ± 0.06 kg/d for HF, SF, and DL, respectively). In year 1, daily feed intake was similar (9.03 vs. 10.0 ± 0.96 kg/steer; P = 0.17) among SF and, DL systems. In year 2, intake was greater for DL than SF (10.1 vs. 8.3 ± 0.25; P < 0.01). Feed efficiency (G:F) was greater for HF steers vs. SF or DL steers in year 1 (P < 0.01). (P=0.91; 0.04, 0.11, 0.09, ± 0.04 for year 1 HF, SF, and DL respectively). In year 2, G:F did not differ among treatments (P= 0.50; 0.16, 0.09, 0.08 HF, SF, DL respectively). Forage utilization was not quantified; these values represent gain per unit of purchased feed delivered, a metric favoring groups fed at lower rates. Preconditioning costs were 73.50, 175.12 and 167.20 $/steer (year 1) and 53.58, 152.72, and 141.68 $/steer (year 2; HF, SF, and DL respectively). These systems resulted in losses of -57.89, -67.59, and -58.80 $/steer (SE = 4.99; P= 0.38) in year 1, and -28.35,-80.00, and -64.55 $/steer (SE = 17.39; P = 0.18) in year 2 for HF, SF, and DL. Price premiums of 10.61, 10.51, and 9.18 $/45.4 kg (SE = 0.85; P=0.46) in year 1 and 5.79, 14.01, and 11.31 $/45.4 kg (SE = 3.25; P=0.27) in year 2 would be required for HF, SF, and DL to be par with sale at weaning. Overall preconditioning was unprofitable for both years and would require substantial price premiums. Although a lower intensity pasture system reduced overall input cost, it did not result in profitability. Providing ad libitum access to a diet while on pasture did not result in any advantages over drylot based systems.

Purpose: Ischemic preconditioning (IPC) has been used to protect myocardial cells against ischemia-reperfusion injury and is recently used for improving exercise performance. It is unknown whether a remote bout of IPC (RIPC) to tissue not involved in exercise can induce similar exercise improvements and what “dose” of IPC is necessary to induce exercise performance benefits. This study determined if unilateral and bilateral upper limb RIPC improves lower body anaerobic power output. Methods: Using two randomized, single blind, crossover study designs, we studied 43 young recreationally active adults. For study 1, unilateral RIPC was used and a sham control condition involved the inflation of blood pressure cuffs to 10 mm Hg. For study 2, the ischemic stimuli were increased to bilateral occlusion while the sham control condition used was 0 mm Hg of occlusion pressure. After the RIPC treatment, subjects completed four 30 s Wingate anaerobic tests on a Monark cycle ergometer with 2 min passive rest between trials. Results: In the unilateral occlusion trial, peak power, mean power, and fatigue index were not different between the two conditions at every Wingate test. In the bilateral occlusion trial, peak power was elevated in the RIPC condition than in the sham control for the fourth Wingate test (p<0.05). Additionally, compared with the sham control, mean power was greater in the RIPC condition during the first and fourth Wingate tests (both p<0.05). Conclusion: Remote ischemic preconditioning applied bilaterally increased lower body power output over a series of Wingate anaerobic tests. Unilateral RIPC, however, had no effect on any of the performance variables, suggesting that there is a threshold for the amount of target tissue needed to elicit anaerobic performance benefits. / text

A steady-state, single phase subchannel solver was created for the purpose of integration into a multi-physics nuclear fuel performance code. Since applications of such a code include full nuclear reactor core flow simulation, a thorough investigation of efficient solution techniques is a requirement. Execution time profiling found that formation of the Jacobian matrix required by the nonlinear Newton solve was found to be the most time-consuming step in solution of the subchannel equations, so several techniques were tested to minimize the time spent on this task, such as finite difference and the formation of an approximate Jacobian. Simple Jacobian lagging was shown to be very effective at reducing the total time computing the Jacobian throughout the Newton iteration process. Various linear solution techniques were investigated with the subchannel equations, such as the generalized minimal residual method (GMRES) and the aggregation- based algebraic multigrid method (AGMG). A number of physics-based preconditioners were created, based on a simplified formulation with no crossflow between subchannels, and it was found that of the preconditioners developed for this research, the most promising was a preconditioner that fully decoupled the subchannels by ignoring crossflow, conduction, and turbulent momentum exchange between subchannels. This independence between subchannels makes the task of parallelization in the preconditioner to be very feasible. However, AGMG clearly proved to be the most efficient linear solution technique for the subchannel equations, solving the linear systems in less than 5 percent of the time required for preconditioned GMRES.

Les cellules souches multipotentes dérivées du stroma de la moelle osseuse (MSCs) sont des candidates idéales pour des applications en ingénierie tissulaire. Actuellement un grand nombre d’essais cliniques utilisent ces MSCs dans le but de développer des thérapies innovantes. Dans les travaux de cette thèse, nous avons développé deux stratégies de préconditionnement cellulaire dans le but d’optimiser la fonctionnalité des MSCs pour des applications d’ingénierie tissulaire osseuse. La mort massive des MSCs en post-implantation réduit considérablement les bénéfices potentiels de ce type de thérapie. Bien que cette mort massive soit multifactorielle, l’environnement ischémique hostile auquel les cellules doivent faire face une fois implantées semble en être la cause principale. La première stratégie visait à augmenter la survie des hMSCs en conditions ischémiques. Nous avons pu montrer qu’un préconditionnement par quiescence induit une modification du profil métabolique des hMSCs améliorant ainsi leur survie jusqu’à 14 jours dans un modèle d’ischémie in vitro et 7 jours in vivo. Cette modification est caractérisée par (i) une orientation du métabolisme OXPHOS vers un métabolisme glycolytique, et (ii) une activation des voies pro-survie via l’inhibition de mTORC1 et l’activation de l’autophagie. La seconde stratégie visait à induire aux hMSCs un phénotype pro-ostéogène susceptible de favoriser la formation osseuse. Pour cela, les hMSCs ont été prédifférenciées vers la voie adipogénique (AD) ; une voie de différenciation des hMSCs connue pour sa proximité avec la voie ostéogénique. Il s’avère que les hMSCs prédifférenciées (AD+) sont engagées non seulement dans la voie de l’adipogénèse mais aussi dans celle de l’ostéogénèse. Ces hMSCs-AD+ démontrent des potentiels ostéogènes direct et paracrin améliorés, et elles sont capables de former 5-fois plus de tissu osseux in vivo. / Bone marrow stromal derived multipotent stem cells (MSCs) are most suited cells for tissue engineering applications. Nowadays, numerous clinical trials use these MSCs in order to develop new innovative therapies. In the present work, we developed two preconditioning strategies with the aim of improving MSCs functionality for bone tissue engineering. Massive cell death upon implantation drastically reduces the potentials benefits of such MSCs- based therapies. The ischemic hostile environment that cells faces upon implantation is, not the sole, but surely the prime factor responsible for this cell-death. The first strategy aimed at improving hMSCs survival in ischemic conditions. We were able to demonstrate that a quiescence preconditioning induces a modification in the hMSCs metabolic profile thus improving their survival for as long as 14 days in an in vitro ischemic model and 7 days in vivo. This modification is characterized by (i) a shift from an OXPHOS- dependent metabolism towards a glycolytic metabolism, and (ii) activation of pro-survival pathways via mTORC1 inhibition and autophagy activation. The second strategy was to induce a pro-osteogenic phenotype likely favorable for bone formation. To this aim, hMSCs were predifferentiated toward the adipogenic lineage (AD); an hMSCs lineage known to be closely related to the osteogenic one. It appears that predifferentiated hMSCs (AD+) are not only committed towards the adipogenic lineage but also towards the osteogenic one. These hMSCs-AD+ exhibit enhanced direct and paracrine pro-osteogenic potentials, as a result, they are capable of inducing bone tissue formation 5-times more in vivo. These two strategies might enhance the therapeutic outcomes of MSCs-based products for bone tissue engineering applications.

The MSU TURBO code, distributed to U.S. engine companies by NASA Glenn, is a heavily used parallel compressible Reynolds-averaged Navier-Stokes flow solver for multistage turbomachinery flows, primarily for compressible flows at subsonic and transonic speeds. Many low speed turbomachinery flows in aerial vehicles or marine propulsion systems can not be effectively addressed by compressible flow solvers. It is well known that compressible flow equations face difficulties at low Mach number due to the large disparity of the acoustic and convective wave speeds. The current study is to develop and implement the computational capability for flow simulations at low Mach number, or incompressible Mach regime, under the framework of the MSU TURBO code. This is accomplished by applying a global preconditioning scheme to the unsteady term of the compressible governing equations and solving the conservative Riemann flux based on primitive variables. The preconditioning scheme is a single parameter diagonal matrix depending on a reference Mach number which represents the global flow properties in the flow simulation. For flows in rotating machines where speed varies along the radial direction from the axis of the rotation, it is found that a modified preconditioning parameter is necessary to assure numerical stability in simulating low Mach number rotating flows. The effectiveness of the modified preconditioning scheme has been analyzed, under various flow conditions, through Fourier footprints and validated by numerical investigations. The development of a preconditioned structured turbomachinery flow solver was accomplished in this dissertation. The conservative form of the governing equations were cast in the non-inertial relative rotating frame in terms of primitive variables and absolute velocity vectors. Characteristic-based boundary conditions, with implicit treatment of the source term resulting from the rotating relative frame, are derived for internal and external flows. The implicit finite volume scheme is developed for the preconditioned scheme with the flux Jacobians evaluated by either a flux approximate method or flux-vector-splitting. The viscous flux is also treated implicitly, and an analytic form of viscous flux Jacobians was developed in the preconditioned flow solver to reduce numerical uncertainties, and computing time. A series of flow simulations have been carried out by this preconditioned unsteady turbomachinery flow solver. The simulations of viscous boundary layer development over flat plates at very low Mach numbers demonstrate the effectiveness of the preconditioning algorithm. Computations of compressor rotor, and rotor/stator at subsonic, and transonic flow regions with acceptable results indicate that the preconditioned TURBO solver is compatible with the compressible version of the TURBO solver for subsonic and transonic flows. Moderate improvement in numerical convergence for flows in a rotating frame with mixed flow speeds is observed in the case of a tiltrotor blade at hover. The marine propeller simulation demonstrates the accomplishment of the preconditioned TURBO solver for an incompressible flow simulation. In the simulation of a low speed centrifugal compressor, the preconditioned TURBO is able to predicate the wake locations accurately.

Ischemic injury is a common and debilitating outcome of natural illness and as a complication of commonly performed medical procedures. Whereas naturally occurring ischemic insults are often the result of unpredictable events, such as in the case of stroke or heart attack, the risk of operative and perioperative ischemia is somewhat better characterized in the clinical setting. Given the prevalence and severity of outcomes in ischemic injury, there is significant interest in developing better pharmacological and procedural approaches to improve patient outcomes. One approach that has shown significant promise in the laboratory setting, particularly in the context of planned medical procedures, is the use of delayed anesthetic preconditioning. Delayed anesthetic preconditioning is a phenomenon whereby a prior exposure to clinical concentrations of commonly used inhaled anesthetics, including isoflurane, induces the production of endogenous protective proteins that are able to provide robust protection against subsequent, potentially toxic, ischemic insults. Although many aspects of delayed anesthetic preconditioning have been previously described, a complete understanding of preconditioning mechanism has yet to emerge. The studies described in this dissertation aim to further our understanding of molecular mechanisms involved in delayed anesthetic preconditioning. In the first project, I used DNA microarray to identify genes that were differentially expressed in adult rat liver, kidney and heart following a clinically relevant exposure to the inhaled anesthetic isoflurane. By selecting those genes that were differentially expressed in multiple tissues, I was able to identify a small group of interesting genes for further study. In my second study, I chose from our list two related genes, metallothioneins I + II, to analyze for a role in anesthetic-mediated protection. Using a combination of approaches, I was able to establish that metallotioneins I + II play an essential role in delayed anesthetic preconditioning. In the final study of this dissertation I explore a possible role for metallothioneins I + II as sensor molecules, involved in detecting cellular oxidative stress. Taken together, these three studies represent an important contribution to our understanding of the mechanisms of delayed anesthetic preconditioning and how they might contribute to protecting against ischemic stroke.

Thesis (MSc)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: Please see fulltext for abstract. / AFRIKAANSE OPSOMMING: Sien asb volteks vir opsomming.

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