Robust scenario formulations for strategic supply chain optimization under uncertainty

Strategic supply chain optimization (SCO) problems are often modelled as a two-stage optimization problem, in which the first-stage variables represent decisions on the development of the supply chain and the second-stage variables represent decisions on the operations of the supply chain. When uncertainty is explicitly considered, the problem becomes an intractable infinite-dimensional optimization problem, which is usually solved approximately via a scenario or a robust approach. This paper proposes a novel synergy of the scenario and robust approaches for strategic SCO under uncertainty. Two formulations are developed, namely, naïve robust scenario formulation and affinely adjustable robust scenario formulation. It is shown that both formulations can be reformulated into tractable deterministic optimization problems if the uncertainty is bounded with the infinity-norm, and the uncertain equality constraints can be reformulated into deterministic constraints without assumption of the uncertainty region. Case studies of a classical farm planning problem and an energy and bioproduct SCO problem demonstrate the advantages of the proposed formulations over the classical scenario formulation. The proposed formulations not only can generate solutions with guaranteed feasibility or indicate infeasibility of a problem, but also can achieve optimal expected economic performance with smaller numbers of scenarios.

The Capital Sculpture of Wells Cathedral, c. 1184-1210

The understudied capital sculpture of Wells Cathedral in Somerset, England (c. 1184-1210) provides ample opportunity of expanding the current scholarship and understanding of interior ecclesiastical sculpture in a West Country cathedral. While the Gothic style of architecture is typically understood as, according to Paul Binski (2014), rational in execution and reception, the capital sculpture at Wells Cathedral has been considered illogical in terms of both its iconography and location within the nave, transepts, and north porch. Utilizing Michael Camille’s post/anti-iconographical approach, this project examines the Wells figural capitals in five case studies: labour, Old and New Testament Scenes, animals and beast fables, busts, and monsters and hybrids. Each group of capitals will be approached with an understanding that this type of art was viewed by people of different classes and professions, with each viewer bringing their own personal experiences and abilities into how they could have read and understood these types of images. Therefore, the capitals at Wells must be read through layers of meaning and interpretation while also considering their locations within the cathedral and how they react and respond to surrounding figural capitals.

The Location of Cultural Authenticity: Identifying the Real and the Fake in Urban Guizhou

This article examines notions of cultural identity and authenticity and how these notions are articulated in the small city of Kaili in Guizhou Province, an ethnically diverse region. Despite its urban status, Kaili has been branded by the local government as a yuanshengtai tourist destination. This Chinese term literally translates as “original ecology” but is used in ordinary conversation to denote a cultural authenticity in which people exist in quiet harmony with nature. Promotional literature uses the term to tout the ethnic cultural practices that mainly occur in the villages of Kaili’s municipal periphery. In contrast, many local urban inhabitants—although amenable to the promotion of Kaili as a tourist destination—have rejected the notion that the city itself could be considered culturally authentic, and proudly declare themselves “fake” ethnic minorities, as against the “genuine” ethnic people of surrounding villages. These small-city inhabitants have also defined themselves against big-city visitors by attributing to the visitors a naïve fascination with cultural authenticity, while themselves remaining aloof from such practices. The cultural authenticity discourse in Kaili has thus facilitated a reordering of social and spatial hierarchies, as blasé small-city residents define themselves against both culturally authentic rural people and authenticity-seeking big-city tourists. In analyzing this, the article draws out the broader implications regarding PRC notions of ethnicity, cultural practices, heritage, and identity.

Las estatuas-menhir noroccidentales en contexto: conectividad y conexiones materiales durante el Bronce Tardío/Final

Este artículo analiza las estatuas-menhir noroccidentales que se distribuyen en el área comprendida entre los valles del río Duero y el río Miño, pero que descubrimientos recientes han extendido a regiones fuera de este área nuclear. Partiendo de tres aspectos claves para su interpretación (la cronología, su relación con el paisaje y su sentido iconográfico), se examinan las relaciones entre estas formas materiales y un paisaje socio-material de acción específico (las formas socio-materiales de interacción propias del Bronce final atlántico). Para ello, se tiene en cuenta diferentes conexiones materiales (presencia, encuentro, coexistencia, hibridación, etc.) que permiten contextualizar las estatuasmenhir dentro de un proceso histórico particular: la integración del noroeste de la península Ibérica en un contexto de relaciones mediterráneo-atlánticas, en la segunda mitad del II milenio a.C.

James Sacré, a writing of life gesture

In French contemporary poetry, some poets have wished to return to —and so to increase the value of— the enunciation of the poetic subject. In such poetic scenario, the poet James Sacré exemplifies a new approach that tries to re-establish contact with the expression of the poetic subject, albeit always avoiding the pitfalls of excessive ornamentation and poetic effusiveness. Based on the use of simple language, this approach attaches value to legibility and does not hesitate to tap into the most banal or dullest aspects of reality. This article studies one of the procedures used by the poet to reestablish the expression of the poetic subject. This procedure seeks to rewrite life gestures—a technique that evinces an unavoidable relationship between life and poetic words in the work of James Sacré.

Data Mining for Network Intrusion Detection : A comparison of data mining algorithms and an analysis of relevant features for detecting cyber-attacks

Data mining can be defined as the extraction of implicit, previously un-known, and potentially useful information from data. Numerous re-searchers have been developing security technology and exploring new methods to detect cyber-attacks with the DARPA 1998 dataset for Intrusion Detection and the modified versions of this dataset KDDCup99 and NSL-KDD, but until now no one have examined the performance of the Top 10 data mining algorithms selected by experts in data mining. The compared classification learning algorithms in this thesis are: C4.5, CART, k-NN and Naïve Bayes. The performance of these algorithms are compared with accuracy, error rate and average cost on modified versions of NSL-KDD train and test dataset where the instances are classified into normal and four cyber-attack categories: DoS, Probing, R2L and U2R. Additionally the most important features to detect cyber-attacks in all categories and in each category are evaluated with Weka’s Attribute Evaluator and ranked according to Information Gain. The results show that the classification algorithm with best performance on the dataset is the k-NN algorithm. The most important features to detect cyber-attacks are basic features such as the number of seconds of a network connection, the protocol used for the connection, the network service used, normal or error status of the connection and the number of data bytes sent. The most important features to detect DoS, Probing and R2L attacks are basic features and the least important features are content features. Unlike U2R attacks, where the content features are the most important features to detect attacks.

STARTVerso1: A Randomized Trial of Faldaprevir Plus Pegylated Interferon/Ribavirin for Chronic HCV Genotype-1 Infection

BACKGROUND & AIMS: The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection. METHODS: Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24. Other patients received PegIFN/RBV until week 48 unless they met futility criteria. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 was achieved by 52%, 79%, and 80% of patients in arms 1, 2, and 3, respectively (estimated difference for arms 2 and 3 vs. arm 1: 27%, 95% confidence interval 17%-36%; and 29%, 95% confidence interval, 19%-38%, respectively; p < 0.0001 for both). Early treatment success was achieved by 87% (arm 2) and 89% (arm 3) of patients, of whom 86% and 89% achieved SVR12. Adverse event rates were similar among groups; few adverse events led to discontinuation of all regimen components. CONCLUSIONS: Faldaprevir plus PegIFN/RBV significantly increased SVR12, compared with PegIFN/RBV, in treatment-naïve patients with HCV genotype-1 infection. No differences were seen in responses of patients given faldaprevir once daily at 120 or 240 mg.

Rôles de deux corécepteurs impliqués dans le maintien des cellules T mémoires CD8+ et la maturation des cellules dendritiques

La reconnaissance d’un antigène présenté par les cellules présentatrices d’antigène induit la prolifération et la différenciation des lymphocytes T naïfs en lymphocytes T effecteurs et mémoires. Cette reconnaissance se fait par l’interaction du récepteur des cellules T (TCR) des lymphocytes T et le complexe CMH-peptide présent à la surface des DC. Cependant, des signaux additionnels sont requis, une meilleure activation des lymphocytes T implique des corécepteurs présents à la surface de ces deux types cellulaires. Après l’élimination de l’antigène, la plupart des lymphocytes T effecteurs vont mourir. Une petite population de lymphocytes T va persister pour se différencier en lymphocytes T mémoires capables de protéger l’organisme contre une réinfection. Les signaux qui contrôlent le maintien des lymphocytes T mémoires sont encore mal compris. Pour comprendre le rôle de la molécule de costimulation 4-1BB dans le maintien des lymphocytes T CD8 mémoires, nous avons émis l’hypothèse que l’état de phosphorylation de la protéine adaptatrice TRAF1, qui se lie à 4-1BB, module le maintien des lymphocytes T CD8 mémoires. Ainsi, nous avons montré par des expériences de spectrométrie de masse que TRAF1 s’associe préférentiellement à TBK1 lorsqu’elle n’est pas phosphorylée. Nous avons aussi montré que la présence de TRAF1 est requise pour stabiliser TBK1 au récepteur 4-1BB après stimulation des lymphocytes T. Par ailleurs, les lymphocytes T CD8 OT-I TRAF1-/- reconstituées avec un mutant phospho-déficient de TRAF1 (S139A) et ensuite différenciées en lymphocytes T mémoires in vitro induisent une activation de la voie de signalisation NF-ĸB contrairement à ceux exprimant la forme phospho-mimétique de TRAF1 (S139D). Ces premières études démontrent l’importance de l’état de phosphorylation de TRAF1 en aval de 4-1BB dans les cellules T. Dans la seconde partie, nous avons évalué le rôle d’un autre corécepteur; la neuropiline 1, dans la maturation des DC. A cet effet, nous avons émis l’hypothèse que l’interaction de la neuropiline 1 et ses ligands contribuerait à la fonction des DC. Nous avons démontré que l’absence de la neuropiline 1 n’a pas d’effet sur la maturation au LPS des DC. Cependant, la présence du VEGF (un ligand de Nrp-1) inhibe la maturation des DC dérivées de la moelle osseuse. Notre étude a démontré que VEGF inhibe l’expression des molécules de costimulation, la sécrétion des cytokines pro inflammatoires et la signalisation TLR4 principalement les voies MAP Kinase et NF-ĸB. Contrairement aux résultats avec les cellules WT, VEGF n’est pas capable d’affecter la maturation, la sécrétion des cytokines et la signalisation TLR4 des DC Nrp1-Lyz où la neuropiline 1 est délétée. Ainsi, nos résultats ont démontré que VEGF inhibe la maturation des DC de façon Nrp1-dépendante. Enfin, l’analyse des molécules partenaires de la neuropiline 1 montre que Nrp1, VEGF et TLR4 se retrouvent dans le même complexe. Nos résultats démontrent que VEGF, en présence de la neuropiline 1 est capable d’interagir avec TLR4 pour inhiber la maturation des DC. Toutefois, en absence de la neuropiline1, VEGF n’est pas capable de recruter TLR4 pour réduire l’expression des molécules de costimulation. Ces études sur les corécepteurs pourraient être importantes dans l’élaboration de nouvelles approches vaccinales.

An investigation of Hebbian phase sequences as assembly graphs

Hebb proposed that synapses between neurons that fire synchronously are strengthened, forming cell assemblies and phase sequences. The former, on a shorter scale, are ensembles of synchronized cells that function transiently as a closed processing system; the latter, on a larger scale, correspond to the sequential activation of cell assemblies able to represent percepts and behaviors. Nowadays, the recording of large neuronal populations allows for the detection of multiple cell assemblies. Within Hebb's theory, the next logical step is the analysis of phase sequences. Here we detected phase sequences as consecutive assembly activation patterns, and then analyzed their graph attributes in relation to behavior. We investigated action potentials recorded from the adult rat hippocampus and neocortex before, during and after novel object exploration (experimental periods). Within assembly graphs, each assembly corresponded to a node, and each edge corresponded to the temporal sequence of consecutive node activations. The sum of all assembly activations was proportional to firing rates, but the activity of individual assemblies was not. Assembly repertoire was stable across experimental periods, suggesting that novel experience does not create new assemblies in the adult rat. Assembly graph attributes, on the other hand, varied significantly across behavioral states and experimental periods, and were separable enough to correctly classify experimental periods (Naïve Bayes classifier; maximum AUROCs ranging from 0.55 to 0.99) and behavioral states (waking, slow wave sleep, and rapid eye movement sleep; maximum AUROCs ranging from 0.64 to 0.98). Our findings agree with Hebb's view that assemblies correspond to primitive building blocks of representation, nearly unchanged in the adult, while phase sequences are labile across behavioral states and change after novel experience. The results are compatible with a role for phase sequences in behavior and cognition.

Analisi del ruolo del porto di Ravenna nell’import/export di prodotti ortofrutticoli

L'elaborato tratta il ruolo del porto di Ravenna nell'import/export di prodotti ortofrutticoli. Dopo una accurata analisi dei dati, lo studio delle rotte marittime e l'uso di Dbms per gestire un database complesso, si propone un modello di programmazione lineare intera su un problema di ship routing, ship scheduling e full ship-load balancing. L'obiettivo è di massimizzare il profitto derivante da un prezzo di vendita e soggetto ai vari costi della logistica. Il modello sceglie la rotta ottimale da effettuare, in termini di ordine di visita dei vari porti che hanno un import e un export dei prodotti studiati. Inoltre, è in grado di gestire lo scorrere del tempo, fornendo come soluzione il giorno ottimale di visita dei vari porti considerati. Infine, trova la ripartizione ottima del numero di container a bordo della nave per ogni tipologia di prodotto.

Schedulazione delle rotte marittime nel settore ortofrutticolo. Modelli e Metodi

Il trasporto marittimo è una delle modalità più utilizzate soprattutto per la movimentazione di grandi volumi di prodotti tra i continenti in quanto è a basso costo, sicuro e meno inquinante rispetto ad altri mezzi di movimentazione. Ai giorni nostri è responsabile di circa l’80% del commercio globale (in volume di carichi trasportati). Il settore del trasporto marittimo ha avuto una lunga tradizione di pianificazione manuale effettuata da progettisti esperti.
 L’obiettivo principale di questa trattazione è stato quello di implementare un modello matematico lineare (MILP, Mixed-Integer Linear Programming Model) per l’ottimizzazione delle rotte marittime nell’ambito del mercato orto-frutticolo che si sviluppa nel bacino del Mediterraneo (problema di Ship-Scheduling). Il modello fornito in questa trattazione è un valido strumento di supporto alle decisioni che può utilizzare uno spedizioniere nell’ambito della pianificazione delle rotte marittime della flotta di navi in suo possesso. Consente di determinare l’insieme delle rotte ottimali che devono essere svolte da un insieme di vettori al fine di massimizzare il profitto complessivo dello spedizioniere, generato nell’arco di tempo considerato. Inoltre, permette di ottenere, per ogni nave considerata, la ripartizione ottimale della merce (carico ottimale).

The Role of G Protein In Alcohol Related Behaviours Using Drosophila melanogaster As A Model

Ethanol, classified as a drug, affects the central nervous system, and its consumption has been linked to the development of several behaviours including tolerance and dependence. Alcohol tolerance is defined as the need for higher doses of alcohol to induce the same changes observed in the initial exposure or where repetitive exposures of the same alcohol dose induce a lower response. Ethanol has been shown to interact with numerous targets and ultimately influence both short and long term adaptation at the cellular and molecular level in brain [1]. These adaptation processes are likely to involve signalling molecules: our work has focussed on G proteins gene expression. Using both wild type and several mutant fruit fly (Drosophila melanogaster) as a model for behaviour and molecular studies, we observed significant increases in sedation time (ST50) in response to alcohol (P<0.001) Fig.A. We also observed a consistent and significant decrease of Gq protein mRNA expression in Drosophila dUNC and DopR2 mutants chronically exposed to alcohol (*P<0.05). Fig B. Method: Six male flies were observed in drosophila polystyrene 25 x 95mm transparent vial in between cotton plugs. To the top plug, 500uL of 100% ethanol was added. Time till 50% of the flies were sedated was recorded on each day following the schedule. Fig. C (n=4-6). Using RT-PCR, we also quantified G protein mRNA expression levels one hour post initial 30 minutes of ethanol expression on day 1 and day 3 relative to expression in naïve flies.(n=2) [A] Increase in sedation time indicative of tolerance in different mutant lines and wild type flies. Six male flies were used in each experiment and (n= 4-6. ***P<0.001 unpaired t tests). [B] RT-PCR results showing significant reduction in Gq mRNA in flies chronically exposed to alcohol. (n=2. *P<0.05) [C] Alcohol exposure schedule. (1) Kaun K.R., R. Azanchi, Z. Maung, J. Hirsh, U. Heberlein. (2011). A Drosophila model for alcohol reward. Nature Neuroscience. 14 (5), 612–619.

The Role of HBD-2 and HBD-3 in Human T Cell Development

Human β-defensins (hBDs) are a family of cationic peptides able to directly kill a wide range of microorganisms including bacteria, fungi and viruses. In addition to their antimicrobial activities, defensins also contribute to the modulation of both the host innate and adaptive immunity. In this project, we demonstrate that the αCD3/28 co-stimulation of human CD4+ T cells in the presence of 10μg/ml hBD-2 or hBD-3 together causes an up-regulation in numbers of CD4+CD69+CD25+ and CD4+CD69-CD25+ T cell subsets, indicating that the treatment of hBD-2 and 3 enhances CD4+ T cell activation. Consistent with this finding, proliferation assay using CFSE suggests that hBD-2 and hBD-3 treatment in vitro induces the proliferation of CD4+ T cells following by 96hrs culture. Analysis of expression of the regulatory T cells (Tregs) specific marker, FoxP3, reveals a shift in the CD4+CD127-CD25+ Treg subset at 18hrs. However, at the later time point, we found that the percentage of FoxP3+cells decreased in the CD4+CD127-CD25+ Treg population, whereas the presence of the FoxP3+CTLA-4+ Treg subset increased. These data indicate that Treg suppressive function may be potentially defective following the co-incubation of purified T cells with either hBD-2 or hBD-3 for 42hrs in vitro due to the apparent loss of FoxP3 expression. We further characterise the role of hBD-2 and hBD-3 in driving human CD4+ T cells polarisation. Our in vitro data suggests that treatment with hBD-2 and hBD-3 can not only induces effector T cell (Teff) differentiation into RORγt+T-bet+ (Th17/Th1) cells, but can also trigger the differentiation of Treg expressing RORγt and T-bet rather than the master controller of Treg function, FoxP3. This apparent plasticity of T cell phenotype allows them to convert from Treg to Th1/17-like effector T cell phenotype following 18hrs in culture. By 42hrs in culture, treatment with hBD-2 and hBD-3 induced both Teff cell and Treg cell differentiation towards the Th17-like phenotype. Compared with the treatment with hBD-2, treatment with hBD-3 induced a more pronounced effect to increase levels of RORγt in CD4+ T cells. This elevated expression may, in turn, be responsible for the induction of higher IL-17A secretion. Consistent with this idea, it was found that treatment with hBD-3 but not hBD-2 was capable of inducing the higher level of secretion of IL-17A. Additionally, treatment with hBD-3 induced an increased expression of IL-6, which is capable of driving the differentiation of naïve T cells towards IL-17-producing Th17 cells. Functionally, using the Treg suppression assay, the data suggested that hBD-2 may dampen down Treg cell ability to induce suppression of Teff cell activity. Interestingly, co-culture with hBD-2 would also appear to increase Teff cell resistance to Treg immunoregulation in vitro. Further investigation using microarray gene analysis revealed chemokine C-C motif ligand 1 (CCL1) as potential genes responding to hBD-2 treatment. The blockade of CCL1 has been reported to inhibit Treg suppressive function. Thus, this study explored the function of these antimicrobial candidates in regulating CD4+ T cell plasticity which could result in hBD-2 and hBD-3 being able to regulate its own production, but also may regulate Treg and Teff cell development and function, thus strengthening the link between innate and adaptive immunity

Previsão do índice bovespa por meio de redes neurais artificiais: uma análise comparada aos métodos tradicionais de séries de tempo

Forecast is the basis for making strategic, tactical and operational business decisions. In financial economics, several techniques have been used to predict the behavior of assets over the past decades.Thus, there are several methods to assist in the task of time series forecasting, however, conventional modeling techniques such as statistical models and those based on theoretical mathematical models have produced unsatisfactory predictions, increasing the number of studies in more advanced methods of prediction. Among these, the Artificial Neural Networks (ANN) are a relatively new and promising method for predicting business that shows a technique that has caused much interest in the financial environment and has been used successfully in a wide variety of financial modeling systems applications, in many cases proving its superiority over the statistical models ARIMA-GARCH. In this context, this study aimed to examine whether the ANNs are a more appropriate method for predicting the behavior of Indices in Capital Markets than the traditional methods of time series analysis. For this purpose we developed an quantitative study, from financial economic indices, and developed two models of RNA-type feedfoward supervised learning, whose structures consisted of 20 data in the input layer, 90 neurons in one hidden layer and one given as the output layer (Ibovespa). These models used backpropagation, an input activation function based on the tangent sigmoid and a linear output function. Since the aim of analyzing the adherence of the Method of Artificial Neural Networks to carry out predictions of the Ibovespa, we chose to perform this analysis by comparing results between this and Time Series Predictive Model GARCH, developing a GARCH model (1.1).Once applied both methods (ANN and GARCH) we conducted the results' analysis by comparing the results of the forecast with the historical data and by studying the forecast errors by the MSE, RMSE, MAE, Standard Deviation, the Theil's U and forecasting encompassing tests. It was found that the models developed by means of ANNs had lower MSE, RMSE and MAE than the GARCH (1,1) model and Theil U test indicated that the three models have smaller errors than those of a naïve forecast. Although the ANN based on returns have lower precision indicator values than those of ANN based on prices, the forecast encompassing test rejected the hypothesis that this model is better than that, indicating that the ANN models have a similar level of accuracy . It was concluded that for the data series studied the ANN models show a more appropriate Ibovespa forecasting than the traditional models of time series, represented by the GARCH model

Évaluation du ratio de couverture optimal pour un portefeuille d'obligations dans le contexte du marché financier canadien

Il existe une multitude de façons de protéger un portefeuille formé d'obligations contre une variation des taux d'intérêt qui pourrait affecter défavorablement la valeur marchande du portefeuille. L'une d'elles consiste à vendre des contrats à terme sur obligations afin que les variations de la valeur marchande du portefeuille soient compensées par les gains (ou les pertes) sur le marché à terme. Le succès d'une telle opération dépend de l'évaluation du ratio de couverture puisque c'est lui qui déterminera quelle quantité de contrats à terme il faudra vendre pour protéger le portefeuille. L'objectif de cette étude consiste à déterminer, parmi cinq méthodes d'estimation du ratio de couverture (une naïve et quatre théoriques), celle qui permet de minimiser la variance du rendement du portefeuille à couvrir tout en sacrifiant le moins possible en terme de rendement. Pour ce faire, nous avons utilisé neuf portefeuilles formés d'obligations du gouvernement du Canada ayant des caractéristiques (coupon, échéance) très différentes que nous avons couverts en utilisant le contrat à terme sur obligations du gouvernement du Canada qui se transige à la Bourse de Montréal. L'analyse des résultats nous a amené à conclure que la méthode naïve génère de meilleurs résultats que les méthodes théoriques lorsque le portefeuille à couvrir possède des caractéristiques semblables au titre qui sert de couverture. Dans tous les autres cas (où le portefeuille à couvrir a des caractéristiques très différentes du contrat à terme qui sert de couverture), la performance de la méthode naïve est plutôt médiocre, mais aucune autre méthode n'est supérieure aux autres sur une base régulière.