Identifying Individual T Cell Receptors of Optimal Avidity for Tumor Antigens.

Cytotoxic T cells recognize, via their T cell receptors (TCRs), small antigenic peptides presented by the major histocompatibility complex (pMHC) on the surface of professional antigen-presenting cells and infected or malignant cells. The efficiency of T cell triggering critically depends on TCR binding to cognate pMHC, i.e., the TCR-pMHC structural avidity. The binding and kinetic attributes of this interaction are key parameters for protective T cell-mediated immunity, with stronger TCR-pMHC interactions conferring superior T cell activation and responsiveness than weaker ones. However, high-avidity TCRs are not always available, particularly among self/tumor antigen-specific T cells, most of which are eliminated by central and peripheral deletion mechanisms. Consequently, systematic assessment of T cell avidity can greatly help distinguishing protective from non-protective T cells. Here, we review novel strategies to assess TCR-pMHC interaction kinetics, enabling the identification of the functionally most-relevant T cells. We also discuss the significance of these technologies in determining which cells within a naturally occurring polyclonal tumor-specific T cell response would offer the best clinical benefit for use in adoptive therapies, with or without T cell engineering.

Graduating 4th year radiology residents' perception of optimal imaging modalities for neoplasm and trauma: a pilot study from four U.S. universities

OBJECTIVE: Our purpose was to assess 4th year radiology residents' perception of the optimal imaging modality to investigate neoplasm and trauma. MATERIALS AND METHODS: Twenty-seven 4th year radiology residents from four residency programs were surveyed. They were asked about the best imaging modality to evaluate the brain and spine, lungs, abdomen, and the musculoskeletal system. Imaging modalities available were MRI, CT, ultrasound, PET, and X-ray. All findings were compared to the ACR appropriateness criteria. RESULTS: MRI was chosen as the best imaging modality to evaluate brain, spine, abdominal, and musculoskeletal neoplasm in 96.3%, 100%, 70.4%, and 63% of residents, respectively. CT was chosen by 88.9% to evaluate neoplasm of the lung. Optimal imaging modality to evaluate trauma was CT for brain injuries (100%), spine (92.6%), lung (96.3%), abdomen (92.6%), and major musculoskeletal trauma (74.1%); MRI was chosen for sports injury (96.3%). There was agreement with ACR appropriateness criteria. CONCLUSION: Residents' perception of the best imaging modalities for neoplasm and trauma concurred with the appropriateness criteria by the ACR.

Life span and reproductive cost explain interspecific variation in the optimal onset of reproduction.

Fitness can be profoundly influenced by the age at first reproduction (AFR), but to date the AFR-fitness relationship only has been investigated intraspecifically. Here, we investigated the relationship between AFR and average lifetime reproductive success (LRS) across 34 bird species. We assessed differences in the deviation of the Optimal AFR (i.e., the species-specific AFR associated with the highest LRS) from the age at sexual maturity, considering potential effects of life history as well as social and ecological factors. Most individuals adopted the species-specific Optimal AFR and both the mean and Optimal AFR of species correlated positively with life span. Interspecific deviations of the Optimal AFR were associated with indices reflecting a change in LRS or survival as a function of AFR: a delayed AFR was beneficial in species where early AFR was associated with a decrease in subsequent survival or reproductive output. Overall, our results suggest that a delayed onset of reproduction beyond maturity is an optimal strategy explained by a long life span and costs of early reproduction. By providing the first empirical confirmations of key predictions of life-history theory across species, this study contributes to a better understanding of life-history evolution.

Optimal slopes and speeds in uphill ski mountaineering: a laboratory study.

The purpose of this study was to estimate the energy cost of linear (EC) and vertical displacement (ECvert), mechanical efficiency and main stride parameters during simulated ski mountaineering at different speeds and gradients, to identify an optimal speed and gradient that maximizes performance. 12 subjects roller skied on a treadmill at three different inclines (10, 17 and 24 %) at three different speeds (approximately 70, 80 and 85 % of estimated peak heart rate). Energy expenditure was calculated by indirect calorimetry, while biomechanical parameters were measured with an inertial sensor-based system. At 10 % there was no significant change with speed in EC, ECvert and mechanical efficiency. At 17 and 24 % the fastest speed was significantly more economical. There was a significant effect of gradient on EC, ECvert and mechanical efficiency. The most economical gradient was the steepest one. There was a significant increase of stride frequency with speed. At steep gradients only, relative thrust phase duration decreased significantly, while stride length increased significantly with speed. There was a significant effect of gradient on stride length (decrease with steepness) and relative thrust phase duration (increase with steepness). A combination of a decreased relative thrust phase duration with increased stride length and frequency decreases ECvert. To minimize the energy expenditure to reach the top of a mountain and to optimize performance, ski-mountaineers should choose a steep gradient (~24 %) and, provided they possess sufficient metabolic scope, combine it with a fast speed (~6 km h(-1)).

Analyse de réseau piéton et gestion scolaire: sinuosité, centricité et transport optimal régularisé

Que ce soit d'un point de vue, urbanistique, social, ou encore de la gouvernance, l'évolution des villes est un défi majeur de nos sociétés contemporaines. En offrant la possibilité d'analyser des configurations spatiales et sociales existantes ou en tentant de simuler celles à venir, les systèmes d'information géographique sont devenus incontournables dans la gestion et dans la planification urbaine. En cinq ans la population de la ville de Lausanne est passée de 134'700 à 140'570 habitants, alors que les effectifs de l'école publique ont crû de 12'200 à 13'500 élèves. Cet accroissement démographique associé à un vaste processus d'harmonisation de la scolarité obligatoire en Suisse ont amené le Service des écoles à mettre en place et à développer en collaboration avec l'université de Lausanne des solutions SIG à même de répondre à différentes problématiques spatiales. Établies en 1989, les limites des établissements scolaires (bassins de recrutement) ont dû être redéfinies afin de les réadapter aux réalités d'un paysage urbain et politique en pleine mutation. Dans un contexte de mobilité et de durabilité, un système d'attribution de subventions pour les transports publics basé sur la distance domicile-école et sur l'âge des écoliers, a été conçu. La réalisation de ces projets a nécessité la construction de bases de données géographiques ainsi que l'élaboration de nouvelles méthodes d'analyses exposées dans ce travail. Cette thèse s'est ainsi faite selon une dialectique permanente entre recherches théoriques et nécessités pratiques. La première partie de ce travail porte sur l'analyse du réseau piéton de la ville. La morphologie du réseau est investiguée au travers d'approches multi-échelles du concept de centralité. La première conception, nommée sinuo-centralité ("straightness centrality"), stipule qu'être central c'est être relié aux autres en ligne droite. La deuxième, sans doute plus intuitive, est intitulée centricité ("closeness centrality") et exprime le fait qu'être central c'est être proche des autres (fig. 1, II). Les méthodes développées ont pour but d'évaluer la connectivité et la marchabilité du réseau, tout en suggérant de possibles améliorations (création de raccourcis piétons). Le troisième et dernier volet théorique expose et développe un algorithme de transport optimal régularisé. En minimisant la distance domicile-école et en respectant la taille des écoles, l'algorithme permet de réaliser des scénarios d'enclassement. L'implémentation des multiplicateurs de Lagrange offre une visualisation du "coût spatial" des infrastructures scolaires et des lieux de résidence des écoliers. La deuxième partie de cette thèse retrace les aspects principaux de trois projets réalisés dans le cadre de la gestion scolaire. À savoir : la conception d'un système d'attribution de subventions pour les transports publics, la redéfinition de la carte scolaire, ou encore la simulation des flux d'élèves se rendant à l'école à pied. *** May it be from an urbanistic, a social or from a governance point of view, the evolution of cities is a major challenge in our contemporary societies. By giving the opportunity to analyse spatial and social configurations or attempting to simulate future ones, geographic information systems cannot be overlooked in urban planning and management. In five years, the population of the city of Lausanne has grown from 134'700 to 140'570 inhabitants while the numbers in public schools have increased from 12'200 to 13'500 students. Associated to a considerable harmonisation process of compulsory schooling in Switzerland, this demographic rise has driven schooling services, in collaboration with the University of Lausanne, to set up and develop GIS capable of tackling various spatial issues. Established in 1989, the school districts had to be altered so that they might fit the reality of a continuously changing urban and political landscape. In a context of mobility and durability, an attribution system for public transport subventions based on the distance between residence and school and on the age of the students was designed. The implementation of these projects required the built of geographical databases as well as the elaboration of new analysis methods exposed in this thesis. The first part of this work focuses on the analysis of the city's pedestrian network. Its morphology is investigated through multi-scale approaches of the concept of centrality. The first conception, named the straightness centrality, stipulates that being central is being connected to the others in a straight line. The second, undoubtedly more intuitive, is called closeness centrality and expresses the fact that being central is being close to the others. The goal of the methods developed is to evaluate the connectivity and walkability of the network along with suggesting possible improvements (creation of pedestrian shortcuts).The third and final theoretical section exposes and develops an algorithm of regularised optimal transport. By minimising home to school distances and by respecting school capacity, the algorithm enables the production of student allocation scheme. The implementation of the Lagrange multipliers offers a visualisation of the spatial cost associated to the schooling infrastructures and to the student home locations. The second part of this thesis recounts the principal aspects of three projects fulfilled in the context of school management. It focuses namely on the built of an attribution system for public transport subventions, a school redistricting process and on simulating student pedestrian flows.

Optimal Traffic Grooming in WDM using Lighttours

Recent developments in optical communications have allowed simpler optical devices to improve network resource utilization. As such, we propose adding a lambda-monitoring device to a wavelength-routing switch (WRS) allowing better performance when traffic is routed and groomed. This device may allow a WRS to aggregate traffic over optical routes without incurring in optical-electrical-optical conversion for the existing traffic. In other words, optical routes can be taken partially to route demands creating a sort of "lighttours". In this paper, we compare the number of OEO conversions needed to route a complete given traffic matrix using either lighttours or lightpaths

Improving the efficiency of PV low-power processing circuits by selecting an optimal inductor current of the DC/DC converter

In the context of autonomous sensors powered by small-size photovoltaic (PV) panels, this work analyses how the efficiency of DC/DC-converter-based power processing circuits can be improved by an appropriate selection of the inductor current that transfers the energy from the PV panel to a storage unit. Each component of power losses (fixed, conduction and switching losses) involved in the DC/DC converter specifically depends on the average inductor current so that there is an optimal value of this current that causes minimal losses and, hence, maximum efficiency. Such an idea has been tested experimentally using two commercial DC/DC converters whose average inductor current is adjustable. Experimental results show that the efficiency can be improved up to 12% by selecting an optimal value of that current, which is around 300-350 mA for such DC/DC converters.

Assessing functional relations in single-case designs: Quantitative proposals in the context of the evidence-based movement

In the context of the evidence-based practices movement, the emphasis on computing effect sizes and combining them via meta-analysis does not preclude the demonstration of functional relations. For the latter aim, we propose to augment the visual analysis to add consistency to the decisions made on the existence of a functional relation without losing sight of the need for a methodological evaluation of what stimuli and reinforcement or punishment are used to control the behavior. Four options for quantification are reviewed, illustrated, and tested with simulated data. These quantifications include comparing the projected baseline with the actual treatment measurements, on the basis of either parametric or nonparametric statistics. The simulated data used to test the quantifications include nine data patterns in terms of the presence and type of effect and comprising ABAB and multiple baseline designs. Although none of the techniques is completely flawless in terms of detecting a functional relation only when it is present but not when it is absent, an option based on projecting split-middle trend and considering data variability as in exploratory data analysis proves to be the best performer for most data patterns. We suggest that the information on whether a functional relation has been demonstrated should be included in meta-analyses. It is also possible to use as a weight the inverse of the data variability measure used in the quantification for assessing the functional relation. We offer an easy to use code for open-source software for implementing some of the quantifications.

Assigning and combining probabilities in single-case designs: A second study

The present study builds on a previous proposal for assigning probabilities to the outcomes computed using different primary indicators in single-case studies. These probabilities are obtained comparing the outcome to previously tabulated reference values and reflect the likelihood of the results in case there was no intervention effect. The current study explores how well different metrics are translated into p values in the context of simulation data. Furthermore, two published multiple baseline data sets are used to illustrate how well the probabilities could reflect the intervention effectiveness as assessed by the original authors. Finally, the importance of which primary indicator is used in each data set to be integrated is explored; two ways of combining probabilities are used: a weighted average and a binomial test. The results indicate that the translation into p values works well for the two nonoverlap procedures, with the results for the regression-based procedure diverging due to some undesirable features of its performance. These p values, both when taken individually and when combined, were well-aligned with the effectiveness for the real-life data. The results suggest that assigning probabilities can be useful for translating the primary measure into the same metric, using these probabilities as additional evidence on the importance of behavioral change, complementing visual analysis and professional's judgments.

Optimal latent period in a bacteriophage population model structured by infection-age

We study the lysis timing of a bacteriophage population by means of a continuously infection-age-structured population dynamics model. The features of the model are the infection process of bacteria, the death process, and the lysis process which means the replication of bacteriophage viruses inside bacteria and the destruction of them. The time till lysis (or latent period) is assumed to have an arbitrary distribution. We have carried out an optimization procedure, and we have found that the latent period corresponding to maximal fitness (i.e. maximal growth rate of the bacteriophage population) is of fixed length. We also study the dependence of the optimal latent period on the amount of susceptible bacteria and the number of virions released by a single infection. Finally, the evolutionarily stable strategy of the latent period is also determined as a fixed period taking into account that super-infections are not considered

Use of multivariate experimental designs for optimizing the reductive degradation of an azo dye in the presence of redox mediators

The optimization of the anaerobic degradation of the azo dye Remazol golden yellow RNL was performed according to multivariate experimental designs: a 2² full-factorial design and a central composite design (CCD). The CCD revealed that the best incubation conditions (90% color removal) for the degradation of the azo dye (50 mg L- 1) were achieved with 350 mg L- 1 of yeast extract and 45 mL of anaerobic supernatant (free cell extract) produced from the incubation of 650 mg L- 1 of anaerobic microorganisms and 250 mg L- 1 of glucose. A first-order kinetics model best fit the experimental data (k = 0.0837 h- 1, R² = 0.9263).

Estimation of existing cable systems in generator-busbar unit and choice the optimal solution for its modernization

The aim of this master’s thesis is to develop an algorithm to calculate the cable network for heat and power station CHGRES. This algorithm includes important aspect which has an influence on the cable network reliability. Moreover, according to developed algorithm, the optimal solution for modernization cable system from economical and technical point of view was obtained. The conditions of existing cable lines show that replacement is necessary. Otherwise, the fault situation would happen. In this case company would loss not only money but also its prestige. As a solution, XLPE single core cables are more profitable than other types of cable considered in this work. Moreover, it is presented the dependence of value of short circuit current on number of 10/110 kV transformers connected in parallel between main grid and considered 10 kV busbar and how it affects on final decision. Furthermore, the losses of company in power (capacity) market due to fault situation are presented. These losses are commensurable with investment to replace existing cable system.