The stimulation of creative writing on a third grade level

Thesis (Ed.M.)--Boston Universit

ScannerS: Constraining the phase diagram of a complex scalar singlet at the LHC

We present the first version of a new tool to scan the parameter space of generic scalar potentials, ScannerS. The main goal of ScannerS is to help distinguish between different patterns of symmetry breaking for each scalar potential. In this work we use it to investigate the possibility of excluding regions of the phase diagram of several versions of a complex singlet extension of the Standard Model, with future LHC results. We find that if another scalar is found, one can exclude a phase with a dark matter candidate in definite regions of the parameter space, while predicting whether a third scalar to be found must be lighter or heavier. The first version of the code is publicly available and contains various generic core routines for tree level vacuum stability analysis, as well as implementations of collider bounds, dark matter constraints, electroweak precision constraints and tree level unitarity.Comment: 24 pages, 4 figures, 3 tables. Project development webpage - http://gravitation.web.ua.pt/Scanner

Rare autosomal dominant hereditary hemochromatosis associated with SLC40A1 gene: ferroportin disease or type 4 hereditary hemochromatosis?

Ferroportin (FPN1), encoded by the SLC40A1 gene, is the unique cellular iron exporter identified in mammals. FPN1 transfers iron from the intestine and macrophages into the bloodstream. This function is negatively regulated by hepcidin. Mutations in SLC40A1 may affect FPN1 function, originating distinct autosomal dominant diseases: (i) the Ferroportin Disease (FD), due to loss-of-function mutations, is characterized by decreased iron export from enterocytes and severely affected iron transfer in macrophages, giving rise to a marked iron accumulation in spleen and liver; and (ii) the Type 4 Hereditary Hemochromatosis (HH), resulting from gain-of-function mutations conferring resistance to hepcidin-mediated FPN1 degradation and consequently high cellular iron export. In this study, 335 individuals suspected of having non-classic HH were enrolled. Six genes related with iron metabolism were analysed by SSCP, dHPLC or NGS. The latter used TruSeq or Nextera XT libraries and a MiSeq platform (Illumina). Genetic variants found were validated by Sanger sequencing. Predictive consequences at protein level were evaluated using Polyphen-2 and SIFT softwares. From all patients analysed, three SLC40A1 pathogenic variants were detected in heterozygosity in three women: two missense, c.238G>A, p.Gly80Ser and c.610G>A, p.Gly204Ser; and one deletion, c.485_487delTTG; p.Val162del. These variants had been reported in public databases, but they were not known to be present in the Portuguese population. The p.Gly80Ser and the p.Val162del are FPN1 loss-of-function mutations and were found associated with hyperferritinemia and low transferrin saturation (FD). In contrast, the p.Gly204Ser induced a gain of FPN1 function with a full iron export capacity giving the patient a type 4-HH phenotype, which includes iron overload, hyperferritinemia and high transferrin saturation. Detailed clinical evaluation of the suspected patients are useful to unravel the effect of different mutations in FPN1 function, expression and regulation.This work was partially supported by INSA_2013DGH910 and GenomePT (POCI-01-0145-FEDER-022184).info:eu-repo/semantics/publishedVersio

Driver scheduling problem modelling

The Drivers Scheduling Problem (DSP) consists of selecting a set of duties for vehicle drivers, for example buses, trains, plane or boat drivers or pilots, for the transportation of passengers or goods. This is a complex problem because it involves several constraints related to labour and company rules and can also present different evaluation criteria and objectives. Being able to develop an adequate model for this problem that can represent the real problem as close as possible is an important research area.The main objective of this research work is to present new mathematical models to the DSP problem that represent all the complexity of the drivers scheduling problem, and also demonstrate that the solutions of these models can be easily implemented in real situations. This issue has been recognized by several authors and as important problem in Public Transportation. The most well-known and general formulation for the DSP is a Set Partition/Set Covering Model (SPP/SCP). However, to a large extend these models simplify some of the specific business aspects and issues of real problems. This makes it difficult to use these models as automatic planning systems because the schedules obtained must be modified manually to be implemented in real situations. Based on extensive passenger transportation experience in bus companies in Portugal, we propose new alternative models to formulate the DSP problem. These models are also based on Set Partitioning/Covering Models; however, they take into account the bus operator issues and the perspective opinions and environment of the user.We follow the steps of the Operations Research Methodology which consist of: Identify the Problem; Understand the System; Formulate a Mathematical Model; Verify the Model; Select the Best Alternative; Present the Results of the Analysis and Implement and Evaluate. All the processes are done with close participation and involvement of the final users from different transportation companies. The planner‘s opinion and main criticisms are used to improve the proposed model in a continuous enrichment process. The final objective is to have a model that can be incorporated into an information system to be used as an automatic tool to produce driver schedules. Therefore, the criteria for evaluating the models is the capacity to generate real and useful schedules that can be implemented without many manual adjustments or modifications. We have considered the following as measures of the quality of the model: simplicity, solution quality and applicability. We tested the alternative models with a set of real data obtained from several different transportation companies and analyzed the optimal schedules obtained with respect to the applicability of the solution to the real situation. To do this, the schedules were analyzed by the planners to determine their quality and applicability. The main result of this work is the proposition of new mathematical models for the DSP that better represent the realities of the passenger transportation operators and lead to better schedules that can be implemented directly in real situations.Drivers Scheduling Problem, Duties, Modelling

Design and Simulation of THz Quantum Cascade Lasers

Strategies and concepts for the design of THz emitters based on the quantum cascade scheme are analyzed and modeled in terms of a fully three-dimensional Monte Carlo approach; this allows for a proper inclusion of both carrier-carrier and carrier-phonon scattering mechanisms. Starting from the simulation of previously published far-infrared emitters, where no population inversion is achieved, two innovative designs are proposed. The first one follows the well-established chirped-superlattice scheme whereas the second one employs a double-quantum well superlattice to allow energy relaxation through optical phonon emission. For both cases a significant population inversion is predicted at temperatures up to 80 K.Comment: 4 pages, 2 figures, 2 table

Prostaglandin E2 promotes features of replicative senescence in chronically activated human CD8+ T cells.

Prostaglandin E2 (PGE2), a pleiotropic immunomodulatory molecule, and its free radical catalyzed isoform, iso-PGE2, are frequently elevated in the context of cancer and chronic infection. Previous studies have documented the effects of PGE2 on the various CD4+ T cell functions, but little is known about its impact on cytotoxic CD8+ T lymphocytes, the immune cells responsible for eliminating virally infected and tumor cells. Here we provide the first demonstration of the dramatic effects of PGE2 on the progression of human CD8+ T cells toward replicative senescence, a terminal dysfunctional state associated multiple pathologies during aging and chronic HIV-1 infection. Our data show that exposure of chronically activated CD8+ T cells to physiological levels of PGE2 and iso-PGE2 promotes accelerated acquisition of markers of senescence, including loss of CD28 expression, increased expression of p16 cell cycle inhibitor, reduced telomerase activity, telomere shortening and diminished production of key cytotoxic and survival cytokines. Moreover, the CD8+ T cells also produced higher levels of reactive oxygen species, suggesting that the resultant oxidative stress may have further enhanced telomere loss. Interestingly, we observed that even chronic activation per se resulted in increased CD8+ T cell production of PGE2, mediated by higher COX-2 activity, thus inducing a negative feedback loop that further inhibits effector function. Collectively, our data suggest that the elevated levels of PGE2 and iso-PGE2, seen in various cancers and HIV-1 infection, may accelerate progression of CD8+ T cells towards replicative senescence in vivo. Inhibition of COX-2 activity may, therefore, provide a strategy to counteract this effect