Search for the Xb and other hidden-beauty states in the π+π-ϒ{hooked}(1S) channel at ATLAS

This Letter presents a search for a hidden-beauty counterpart of the X(3872) in the mass ranges 10.05--10.31 GeV and 10.40--11.00 GeV, in the channel Xb→π+π−Υ(1S)(→μ+μ−), using 16.2 fb−1 of s√=8 TeV pp collision data collected by the ATLAS detector at the LHC. No evidence for new narrow states is found, and upper limits are set on the product of the Xb cross section and branching fraction, relative to those of the Υ(2S), at the 95% confidence level using the CLS approach. These limits range from 0.8% to 4.0%, depending on mass. For masses above 10.1 GeV, the expected upper limits from this analysis are the most restrictive to date. Searches for production of the Υ(13DJ), Υ(10860), and Υ(11020) states also reveal no significant signals.

Search for long-lived, weakly interacting particles that decay to displaced hadronic jets in proton--proton collisions at s√=8 TeV with the ATLAS detector

A search for the decay of neutral, weakly interacting, long-lived particles using data collected by the ATLAS detector at the LHC is presented. This analysis uses the full dataset recorded in 2012: 20.3 fb−1 of proton--proton collision data at s√=8 TeV. The search employs techniques for reconstructing decay vertices of long-lived particles decaying to jets in the inner tracking detector and muon spectrometer. Signal events require at least two reconstructed vertices. No significant excess of events over the expected background is found, and limits as a function of proper lifetime are reported for the decay of the Higgs boson and other scalar bosons to long-lived particles and for Hidden Valley Z′ and Stealth SUSY benchmark models. The first search results for displaced decays in Z′ and Stealth SUSY models are presented. The upper bounds of the excluded proper lifetimes are the most stringent to date.

Extreme value Birnbaum-Saunders regression models applied to environmental data

Extreme value models are widely used in different areas. The Birnbaum–Saunders distribution is receiving considerable attention due to its physical arguments and its good properties. We propose a methodology based on extreme value Birnbaum–Saunders regression models, which includes model formulation, estimation, inference and checking. We further conduct a simulation study for evaluating its performance. A statistical analysis with real-world extreme value environmental data using the methodology is provided as illustration.

Nonlinear optimization for human-like synchronous movements of a dual arm-hand robotic system

In previous work we have presented a model capable of generating human-like movements for a dual arm-hand robot involved in human-robot cooperative tasks. However, the focus was on the generation of reach-to-grasp and reach-to-regrasp bimanual movements and no synchrony in timing was taken into account. In this paper we extend the previous model in order to accomplish bimanual manipulation tasks by synchronously moving both arms and hands of an anthropomorphic robotic system. Specifically, the new extended model has been designed for two different tasks with different degrees of difficulty. Numerical results were obtained by the implementation of the IPOPT solver embedded in our MATLAB simulator.

Exploring female mice interstrain differences relevant for models of depression

Depression is an extremely heterogeneous disorder. Diverse molecular mechanisms have been suggested to underlie its etiology. To understand the molecular mechanisms responsible for this complex disorder, researchers have been using animal models extensively, namely mice from various genetic backgrounds and harboring distinct genetic modifications. The use of numerous mouse models has contributed to enrich our knowledge on depression. However, accumulating data also revealed that the intrinsic characteristics of each mouse strain might influence the experimental outcomes, which may justify some conflicting evidence reported in the literature. To further understand the impact of the genetic background, we performed a multimodal comparative study encompassing the most relevant parameters commonly addressed in depression, in three of the most widely used mouse strains: Balb/c, C57BL/6, and CD-1. Moreover, female mice were selected for this study taken into account the higher prevalence of depression in women and the fewer animal studies using this gender. Our results show that Balb/c mice have a more pronounced anxious-like behavior than CD-1 and C57BL/6 mice, whereas C57BL/6 animals present the strongest depressive-like trait. Furthermore, C57BL/6 mice display the highest rate of proliferating cells and brain-derived neurotrophic factor (Bdnf) expression levels in the hippocampus, while hippocampal dentate granular neurons of Balb/c mice show smaller dendritic lengths and fewer ramifications. Of notice, the expression levels of inducible nitric oxide synthase (iNos) predict 39.5% of the depressive-like behavior index, which suggests a key role of hippocampal iNOS in depression. Overall, this study reveals important interstrain differences in several behavioral dimensions and molecular and cellular parameters that should be considered when preparing and analyzing experiments addressing depression using mouse models. It further contributes to the literature by revealing the predictive value of hippocampal iNos expression levels in depressive-like behavior, irrespectively of the mouse strain.

Cylindrically symmetric models of gravitational collapse to black holes: a short review

We survey results about exact cylindrically symmetric models of gravitational collapse in General Relativity. We focus on models which result from the matching of two spacetimes having collapsing interiors which develop trapped surfaces and vacuum exteriors containing gravitational waves. We collect some theorems from the literature which help to decide a priori about eventual spacetime matchings. We revise, in more detail, some toy models which include some of the main mathematical and physical issues that arise in this context, and compute the gravitational energy flux through the matching boundary of a particular collapsing region. Along the way, we point out several interesting open problems.

Specification and testing of multiplicative time-varying GARCH models with applications

In this article, we develop a specification technique for building multiplicative time-varying GARCH models of Amado and Teräsvirta (2008, 2013). The variance is decomposed into an unconditional and a conditional component such that the unconditional variance component is allowed to evolve smoothly over time. This nonstationary component is defined as a linear combination of logistic transition functions with time as the transition variable. The appropriate number of transition functions is determined by a sequence of specification tests. For that purpose, a coherent modelling strategy based on statistical inference is presented. It is heavily dependent on Lagrange multiplier type misspecification tests. The tests are easily implemented as they are entirely based on auxiliary regressions. Finite-sample properties of the strategy and tests are examined by simulation. The modelling strategy is illustrated in practice with two real examples: an empirical application to daily exchange rate returns and another one to daily coffee futures returns.

Exploring the role of O-Mannosylation in the modulation of E-Cadherin function in Gastric Cancer cell line models

Dissertação de mestrado em Bioquímica Aplicada – Biomedicina

Evaluating biomaterial-and microfluidic-based 3D tumor models

Cancer is a major cause of morbidity and mortality worldwide, with a disease burden estimated to increase in the coming decades. Disease heterogeneity and limited information on cancer biology and disease mechanisms are aspects that 2D cell cultures fail to address. We review the current "state-of-the-art" in 3D Tissue Engineering (TE) models developed for and used in cancer research. Scaffold-based TE models and microfluidics, are assessed for their potential to fill the gap between 2D models and clinical application. Recent advances in combining the principles of 3D TE models and microfluidics are discussed, with a special focus on biomaterials and the most promising chip-based 3D models.

Associations, causation and model in psychiatry

This paper discusses models, associations and causation in psychiatry. The different types of association (linear, positive, negative, exponential, partial, U shaped relationship, hidden and spurious) between variables involved in mental disorders are presented as well as the use of multiple regression analysis to disentangle interrelatedness amongst multiple variables. A useful model should have internal consistency, external validity and predictive power; be dynamic in order to accommodate new sound knowledge; and should fit facts rather than they other way around. It is argued that whilst models are theoretical constructs they also convey a style of reasoning and can change clinical practice. Cause and effect are complex phenomena in that the same cause can yield different effects. Conversely, the same effect can have a different range of causes. In mental disorders and human behaviour there is always a chain of events initiated by the indirect and remote cause; followed by intermediate causes; and finally the direct and more immediate cause. Causes of mental disorders are grouped as those: (i) which are necessary and sufficient; (ii) which are necessary but not sufficient; and (iii) which are neither necessary nor sufficient, but when present increase the risk for mental disorders.

Single line for assembly just-in-sequence multiple models

Programa Doutoral em Líderes para as Indústrias Tecnológicas

Metabolic engineering with multi-objective optimization of kinetic models

Kinetic models have a great potential for metabolic engineering applications. They can be used for testing which genetic and regulatory modifications can increase the production of metabolites of interest, while simultaneously monitoring other key functions of the host organism. This work presents a methodology for increasing productivity in biotechnological processes exploiting dynamic models. It uses multi-objective dynamic optimization to identify the combination of targets (enzymatic modifications) and the degree of up- or down-regulation that must be performed in order to optimize a set of pre-defined performance metrics subject to process constraints. The capabilities of the approach are demonstrated on a realistic and computationally challenging application: a large-scale metabolic model of Chinese Hamster Ovary cells (CHO), which are used for antibody production in a fed-batch process. The proposed methodology manages to provide a sustained and robust growth in CHO cells, increasing productivity while simultaneously increasing biomass production, product titer, and keeping the concentrations of lactate and ammonia at low values. The approach presented here can be used for optimizing metabolic models by finding the best combination of targets and their optimal level of up/down-regulation. Furthermore, it can accommodate additional trade-offs and constraints with great flexibility.

Development of computational and experimental methods for biomass composition and evaluation of its impact in genome-scale models prediction

The use of genome-scale metabolic models has been rapidly increasing in fields such as metabolic engineering. An important part of a metabolic model is the biomass equation since this reaction will ultimately determine the predictive capacity of the model in terms of essentiality and flux distributions. Thus, in order to obtain a reliable metabolic model the biomass precursors and their coefficients must be as precise as possible. Ideally, determination of the biomass composition would be performed experimentally, but when no experimental data are available this is established by approximation to closely related organisms. Computational methods however, can extract some information from the genome such as amino acid and nucleotide compositions. The main objectives of this study were to compare the biomass composition of several organisms and to evaluate how biomass precursor coefficients affected the predictability of several genome-scale metabolic models by comparing predictions with experimental data in literature. For that, the biomass macromolecular composition was experimentally determined and the amino acid composition was both experimentally and computationally estimated for several organisms. Sensitivity analysis studies were also performed with the Escherichia coli iAF1260 metabolic model concerning specific growth rates and flux distributions. The results obtained suggest that the macromolecular composition is conserved among related organisms. Contrasting, experimental data for amino acid composition seem to have no similarities for related organisms. It was also observed that the impact of macromolecular composition on specific growth rates and flux distributions is larger than the impact of amino acid composition, even when data from closely related organisms are used.

Predicting SO2 pollution incidents by means of additive models with optimum variable selection

The aim of this paper is to predict time series of SO2 concentrations emitted by coal-fired power stations in order to estimate in advance emission episodes and analyze the influence of some meteorological variables in the prediction. An emission episode is said to occur when the series of bi-hourly means of SO2 is greater than a specific level. For coal-fired power stations it is essential to predict emission epi- sodes sufficiently in advance so appropriate preventive measures can be taken. We proposed a meth- odology to predict SO2 emission episodes based on using an additive model and an algorithm for variable selection. The methodology was applied to the estimation of SO2 emissions registered in sampling lo- cations near a coal-fired power station located in Northern Spain. The results obtained indicate a good performance of the model considering only two terms of the time series and that the inclusion of the meteorological variables in the model is not significant.

A critical evaluation of methods for the reconstruction of tissue-specific models

Under the framework of constraint based modeling, genome-scale metabolic models (GSMMs) have been used for several tasks, such as metabolic engineering and phenotype prediction. More recently, their application in health related research has spanned drug discovery, biomarker identification and host-pathogen interactions, targeting diseases such as cancer, Alzheimer, obesity or diabetes. In the last years, the development of novel techniques for genome sequencing and other high-throughput methods, together with advances in Bioinformatics, allowed the reconstruction of GSMMs for human cells. Considering the diversity of cell types and tissues present in the human body, it is imperative to develop tissue-specific metabolic models. Methods to automatically generate these models, based on generic human metabolic models and a plethora of omics data, have been proposed. However, their results have not yet been adequately and critically evaluated and compared. This work presents a survey of the most important tissue or cell type specific metabolic model reconstruction methods, which use literature, transcriptomics, proteomics and metabolomics data, together with a global template model. As a case study, we analyzed the consistency between several omics data sources and reconstructed distinct metabolic models of hepatocytes using different methods and data sources as inputs. The results show that omics data sources have a poor overlapping and, in some cases, are even contradictory. Additionally, the hepatocyte metabolic models generated are in many cases not able to perform metabolic functions known to be present in the liver tissue. We conclude that reliable methods for a priori omics data integration are required to support the reconstruction of complex models of human cells.