Innate and Adaptive Immunity in Orolabial Herpes Simplex

Oral mucosa is a frequent site of primary herpes simplex virus type 1 (HSV-1) infection, whereas intraoral recurrent disease is very rare. Instead, reactivation from latency predominantly results in asymptomatic HSV shedding to saliva or recurrent labial herpes (RLH) with highly individual frequency. The current study aimed to elucidate the role of human oral innate and acquired immune mechanisms in modulation of HSV infection in orolabial region. Saliva was found to neutralize HSV-1, and to protect cells from infection independently of salivary antibodies. Neutralization capacity was higher in saliva from asymptomatic HSV-seropositive individuals compared to subjects with history of RLH or seronegative controls. Neutralization was at least partially associated with salivary lactoferrin content. Further, lactoferrin and peroxidase-generated hypothiocyanite were found to either neutralize HSV-1 or interfere with HSV-1 replication, whereas lysozyme displayed no anti-HSV-1 activity. Lactoferrin was also shown to modulate HSV-1 infection by inhibiting keratinocyte proliferation. RLH susceptibility was further found to be associated with Th2 biased cytokine responses against HSV, and a higher level of anti- HSV-IgG with Th2 polarization, indicating lack of efficiency of humoral response in the control of HSV disease. In a three-dimensional cell culture, keratinocytes were found to support both lytic and nonproductive infection, suggesting HSV persistence in epithelial cells, and further emphasizing the importance of peripheral immune control of HSV. These results suggest that certain innate salivary antimicrobial compounds and Th1 type cellular responses are critically important in protecting the host against HSV disease, implying possible applications in drug, vaccine and gene therapy design.

An efficient total variation algorithm for super-resolution in fetal brain MRI with adaptive regularization.

Although fetal anatomy can be adequately viewed in new multi-slice MR images, many critical limitations remain for quantitative data analysis. To this end, several research groups have recently developed advanced image processing methods, often denoted by super-resolution (SR) techniques, to reconstruct from a set of clinical low-resolution (LR) images, a high-resolution (HR) motion-free volume. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has been quite attracted by Total Variation energies because of their ability in edge preserving but only standard explicit steepest gradient techniques have been applied for optimization. In a preliminary work, it has been shown that novel fast convex optimization techniques could be successfully applied to design an efficient Total Variation optimization algorithm for the super-resolution problem. In this work, two major contributions are presented. Firstly, we will briefly review the Bayesian and Variational dual formulations of current state-of-the-art methods dedicated to fetal MRI reconstruction. Secondly, we present an extensive quantitative evaluation of our SR algorithm previously introduced on both simulated fetal and real clinical data (with both normal and pathological subjects). Specifically, we study the robustness of regularization terms in front of residual registration errors and we also present a novel strategy for automatically select the weight of the regularization as regards the data fidelity term. Our results show that our TV implementation is highly robust in front of motion artifacts and that it offers the best trade-off between speed and accuracy for fetal MRI recovery as in comparison with state-of-the art methods.

Adaptive MCMC methods with applications in environmental and geophysical models

This work presents new, efficient Markov chain Monte Carlo (MCMC) simulation methods for statistical analysis in various modelling applications. When using MCMC methods, the model is simulated repeatedly to explore the probability distribution describing the uncertainties in model parameters and predictions. In adaptive MCMC methods based on the Metropolis-Hastings algorithm, the proposal distribution needed by the algorithm learns from the target distribution as the simulation proceeds. Adaptive MCMC methods have been subject of intensive research lately, as they open a way for essentially easier use of the methodology. The lack of user-friendly computer programs has been a main obstacle for wider acceptance of the methods. This work provides two new adaptive MCMC methods: DRAM and AARJ. The DRAM method has been built especially to work in high dimensional and non-linear problems. The AARJ method is an extension to DRAM for model selection problems, where the mathematical formulation of the model is uncertain and we want simultaneously to fit several different models to the same observations. The methods were developed while keeping in mind the needs of modelling applications typical in environmental sciences. The development work has been pursued while working with several application projects. The applications presented in this work are: a winter time oxygen concentration model for Lake Tuusulanjärvi and adaptive control of the aerator; a nutrition model for Lake Pyhäjärvi and lake management planning; validation of the algorithms of the GOMOS ozone remote sensing instrument on board the Envisat satellite of European Space Agency and the study of the effects of aerosol model selection on the GOMOS algorithm.

A Feedfordward Adaptive Controller to Reduce the Imaging Time of Large-Sized Biological Samples with a SPM-Based Multiprobe Station

The time required to image large samples is an important limiting factor in SPM-based systems. In multiprobe setups, especially when working with biological samples, this drawback can make impossible to conduct certain experiments. In this work, we present a feedfordward controller based on bang-bang and adaptive controls. The controls are based in the difference between the maximum speeds that can be used for imaging depending on the flatness of the sample zone. Topographic images of Escherichia coli bacteria samples were acquired using the implemented controllers. Results show that to go faster in the flat zones, rather than using a constant scanning speed for the whole image, speeds up the imaging process of large samples by up to a 4x factor.

Signs of a vector's adaptive choice: on the evasion of infectious hosts and parasite-induced mortality

Laboratory and field experiments have demonstrated in many cases that malaria vectors do not feed randomly, but show important preferences either for infected or non-infected hosts. These preferences are likely in part shaped by the costs imposed by the parasites on both their vertebrate and dipteran hosts. However, the effect of changes in vector behaviour on actual parasite transmission remains a debated issue. We used the natural associations between a malaria-like parasite Polychromophilus murinus, the bat fly Nycteribia kolenatii and a vertebrate host the Daubenton's bat Myotis daubentonii to test the vector's feeding preference based on the host's infection status using two different approaches: 1) controlled behavioural assays in the laboratory where bat flies could choose between a pair of hosts; 2) natural bat fly abundance data from wild-caught bats, serving as an approximation of realised feeding preference of the bat flies. Hosts with the fewest infectious stages of the parasite were most attractive to the bat flies that did switch in the behavioural assay. In line with the hypothesis of costs imposed by parasites on their vectors, bat flies carrying parasites had higher mortality. However, in wild populations, bat flies were found feeding more based on the bat's body condition, rather than its infection level. Though the absolute frequency of host switches performed by the bat flies during the assays was low, in the context of potential parasite transmission they were extremely high. The decreased survival of infected bat flies suggests that the preference for less infected hosts is an adaptive trait. Nonetheless, other ecological processes ultimately determine the vector's biting rate and thus transmission. Inherent vector preferences therefore play only a marginal role in parasite transmission in the field. The ecological processes rather than preferences per se need to be identified for successful epidemiological predictions.

Testi volgari della seconda metà del sec. XIV attorno ai Visconti

Oggetto della tesi è la poesia volgare prodotta nell'orbita della corte viscontea nel corso del Trecento e del primo Quattrocento. La presente ricerca si propone di illustrare il contesto culturale lombardo e correggere alcuni giudizi di colore avanzati dagli studi positivistici di fine Ottocento e inizio Novecento, attraverso un'indagine rigorosa sui testi scritti attorno ai Visconti, dei quali si propone un'edizione filologicamente sorvegliata, accompagnata da uno studio sulla tradizione manoscritta, da cappelli introduttivi, apparati critici e note di commento. Una prima sezione ospita il corpus di rime dell'aretino Braccio Bracci: tre canzoni {Silenzio posto aveva al dire in rima-, O aspettato dalla giusta verga e lo scambio epistolare fittizio Soldan di Bambilonia et ceterà-Illustri e serenissimo, alto e vero) e quindici sonetti (O tesorier, che 7 bel tesor d'Omero-, Antonio mio, tua fama era inmortale; Deh, non guastare il popol cristiano; O santo Pietro, per Dio, non restare; El tempio tuo, che tu edificasti-, Veggio l'antica, dritta e ferma Scala-, Messer Luigi, vostra nobil fama-, Volse Traian, quando la vedovella-, Firenze, or ti rallegra, or ti conforta-, O infamato da ' lucenti raggi-, Sette sorelle sono a mme venute-, Sempre son stato con gran signoria; Se Ile cose terrene al possesore; Sia con voi pace, signor' fiorentini). La seconda sezione accoglie dodici sonetti attribuiti al fiorentino Marchionne di Matteo Arrighi {Deh, quant 'egli è in villa un bello stare; Omé, e ' mi par che Ila mia rota torca; Acciò che veggi chiaro il mio sonetto; Tu non potrai più bere alle stagioni; O Iscatizza di vii condizione; Se mille volte il dì tu m'uccidessi; Io n'ò 'n dispetto il Sole e Ila Luna; Tanto mi piace l'angelico sono; Lasso, tapino a mme, quando riguardo; Era venuta nella mente mia; Io ti ricordo, caro amico fino; Solo soletto ma non di pensieri). Nella terza sezione si propongono due canzoni viscontee del magister Giovanni da Modena, La mia gravosa e disformata vita e Ne l'ora che la caligin nocturna . La quarta e ultima sezione è dedicata ad alcune poesie anonime viscontee: sei sonetti (Egli è gran tempo, dolce Signor mio; Quela dolce saeta che nel core; Stan le cita lombarde co le chiave; Cesere in arme fu feroce e franco; l'pensava stancar la destra mano; Poniam silenzio a tutti i gran Signori), due ballate (Chi troppo al fuoco si lassa apressare e Io udii già cantare), due Lamenti di Bernabò Visconti in ottava rima (Novo lamento con doglioxo pianto e l'prego Idio eh 'è Signore e Padre, quest'ultimo pronunciato da un tal Matteo da Milano) e una canzone in morte del duca Gian Galeazzo {Fortuna c 'ogni ben mundan remuti).

Investigation and data adaptive analysis of CARS spectra

In this diploma work advantages of coherent anti-Stokes Raman scattering spectrometry (CARS) and various methods of the quantitative analysis of substance structure with its help are considered. The basic methods and concepts of the adaptive analysis are adduced. On the basis of these methods the algorithm of automatic measurement of a scattering strip size of a target component in CARS spectrum is developed. The algorithm uses known full spectrum of target substance and compares it with a CARS spectrum. The form of a differential spectrum is used as a feedback to control the accuracy of matching. To exclude the influence of a background in CARS spectra the differential spectrum is analysed by means of its second derivative. The algorithm is checked up on the simulated simple spectra and on the spectra of organic compounds received experimentally.

Pathological video game use among young Swiss men: the use of monothetic and polythetic formats to distinguish between pathological, excessive and normal gaming

There is no agreement about the distinction between pathological, excessive and normal gaming. The present study compared two classifications for defining pathological gaming: the polythetic format (gamers who met at least half of the criteria) and monothetic format (gamers who met all criteria). Associations with mental, health and social issues were examined to assess differences between subgroups of gamers. A representative sample of 5,663 young Swiss men filled in a questionnaire as part of the ongoing Cohort Study on Substance Use Risk Factors (C-SURF). Game use was assessed with the Game Addiction Scale. Mental, social and physical factors (depression, anxiety, aggressiveness, physical and mental health, social and health consequences), gambling and substance use (illicit drug use, alcohol dependence and problematic cannabis use) were also assessed. The results indicated that monothetic gamers shared problems with polythetic gamers, but were even more inclined to mental health issues (depression, anxiety, and aggressiveness) and were more vulnerable to other dependencies like substance use, alcohol dependence or gambling. A second analysis using Latent Class Analysis confirmed the distinction between monothetic and polythetic gamers. These findings support the use of a monothetic format to diagnose pathological gaming and to differentiate it from excessive gaming.

Simple Heuristics in a Social Game

Simple Heuristics in a Social World invites readers to discover the simple heuristics that people use to navigate the complexities and surprises of environments populated with others. The social world is a terrain where humans and other animals compete with conspecifics for myriad resources, including food, mates, and status, and where rivals grant the decision maker little time for deep thought, protracted information search, or complex calculations. Yet, the social world also encompasses domains where social animals such as humans can learn from one another and can forge alliances with one another to boost their chances of success. According to the book's thesis, the undeniable complexity of the social world does not dictate cognitive complexity as many scholars of rationality argue. Rather, it entails circumstances that render optimization impossible or computationally arduous: intractability, the existence of incommensurable considerations, and competing goals. With optimization beyond reach, less can be more. That is, heuristics--simple strategies for making decisions when time is pressing and careful deliberation an unaffordable luxury--become indispensible mental tools. As accurate as or even more accurate than complex methods when used in the appropriate social environments, these heuristics are good descriptive models of how people make many decisions and inferences, but their impressive performance also poses a normative challenge for optimization models. In short, the Homo socialis may prove to be a Homo heuristicus whose intelligence reflects ecological rather than logical rationality.

A cognitive hierarchy model of behavior in the action commitment game

We apply the cognitive hierarchy model of Camerer et al. (Q J Econ 119(3):861-898, 2004)-where players have different levels of reasoning-to Huck et al. (Games Econ Behav 38:240-264, 2002) discrete version of Hamilton and Slutsky (Games Econ Behav 2:29-46, 1990) action commitment game-a duopoly with endogenous timing of entry. We show that, for an empirically reasonable average number of thinking steps, the model rules out Stackelberg equilibria, generates Cournot outcomes including delay, and outcomes where the first mover commits to a quantity higher than Cournot but lower than Stackelberg leader. We show that a cognitive hierarchy model with quantal responses can explain the most important features of the experimental data on the action commitment game in (2002). In order to gauge the success of the model in fitting the data, we compare it to a noisy Nash model. We find that the cognitive hierarchy model with quantal responses fits the data better than the noisy Nash model.

OERopoly : A Game to Generate Collective Intelligence around OER

Collective Intelligence (CI ) is a phenomenon that emerges at the crossroads of three worlds: Open Educational Resources (OER), Web 2.0 technologies and Online Learning Communities. Building CI for the OER movement means capturing the richness of information, experiences, knowledge and resources, that the movement is constantly generating, in a way that they can be shared and reused for the benefit of the movement itself. The organisation of CI starts from collecting the knowledge and experiences of OER's practitioners and scholars in new creative forms, and then situating this knowledge in a collective 'pot' from where it can be leveraged with new 'intelligent' meanings and toward new 'intelligent' goals. This workshop is an attempt to do so by engaging participants in a CI experience, in which they will contribute to, and at the same time take something from, the existing CI around OER, Web 2.0 technologies and Online Learning Communities.

Genomic evidence for adaptive inversion clines in Drosophila melanogaster.

Clines in chromosomal inversion polymorphisms-presumably driven by climatic gradients-are common but there is surprisingly little evidence for selection acting on them. Here we address this long-standing issue in Drosophila melanogaster by using diagnostic single nucleotide polymorphism (SNP) markers to estimate inversion frequencies from 28 whole-genome Pool-seq samples collected from 10 populations along the North American east coast. Inversions In(3L)P, In(3R)Mo, and In(3R)Payne showed clear latitudinal clines, and for In(2L)t, In(2R)NS, and In(3R)Payne the steepness of the clinal slopes changed between summer and fall. Consistent with an effect of seasonality on inversion frequencies, we detected small but stable seasonal fluctuations of In(2R)NS and In(3R)Payne in a temperate Pennsylvanian population over 4 years. In support of spatially varying selection, we observed that the cline in In(3R)Payne has remained stable for >40 years and that the frequencies of In(2L)t and In(3R)Payne are strongly correlated with climatic factors that vary latitudinally, independent of population structure. To test whether these patterns are adaptive, we compared the amount of genetic differentiation of inversions versus neutral SNPs and found that the clines in In(2L)t and In(3R)Payne are maintained nonneutrally and independent of admixture. We also identified numerous clinal inversion-associated SNPs, many of which exhibit parallel differentiation along the Australian cline and reside in genes known to affect fitness-related traits. Together, our results provide strong evidence that inversion clines are maintained by spatially-and perhaps also temporally-varying selection. We interpret our data in light of current hypotheses about how inversions are established and maintained.