A comparison of immunohistochemical assays and FISH in detecting the ALK translocation in diagnostic histological and cytological lung tumor material.

Introduction: Detection of the ALK rearrangement in a solid tumor gives these patients the option of crizotinib as an oral form of anticancer treatment. The current test of choice is fluorescence in situ hybridization (FISH), but various cheaper and more convenient immunohistochemical (IHC) assays have been proposed as alternatives. 
Methods: Fifteen FISH-positive cases from patients, seven with data on crizotinib therapy and clinical response, were evaluated for the presence of ALK protein using three different commercially available antibodies: D5F3, using the proprietary automated system (Ventana), ALK1 (Dako), and 5A4 (Abcam). A further 14 FISH-negative and three uncertain (<15% rearrangement detected) cases were also retrieved. Of the total 32 specimens, 17 were excisions and 15 were computed tomography-guided biopsies or cytological specimens. All three antibodies were applied to all cases. Antibodies were semiquantitatively scored on intensity, and the proportion of malignant cells stained was documented. Cutoffs were set by receiver operating curve analysis for positivity to optimize correct classification. 
Results: All three IHC assays were 100% specific but sensitivity did vary: D5F3 86%, ALK 79%, 5A4 71%. Intensity was the most discriminating measure overall, with a combination of proportion and intensity not improving the test. No FISH-negative IHC-positive cases were seen. Two FISH-positive cases were negative with all three IHC assays. One of these had been treated with crizotinib and had failed to show clinical response. The other harbored a second driving mutation in the EGFR gene.
Conclusions: IHC with all three antibodies is especially highly specific (100%) although variably sensitive (71%-86%), specifically in cases with scanty material. D5F3 assay was most sensitive in these latter cases. Occasional cases are IHC-positive but FISH-negative, suggesting either inaccuracy of one assay or occasional tumors with ALK rearrangement that do not express high levels of ALK protein.

Assessment of turbulence model predictions for a centrifugal compressor simulation

Steady-state computational fluid dynamics (CFD) simulations are an essential tool in the design process of centrifugal compressors. Whilst global parameters, such as pressure ratio and efficiency, can be predicted with reasonable accuracy, the accurate prediction of detailed compressor flow fields is a much more significant challenge. Much of the inaccuracy is associated with the incorrect selection of turbulence model. The need for a quick turnaround in simulations during the design optimisation process, also demands that the turbulence model selected be robust and numerically stable with short simulation times.
In order to assess the accuracy of a number of turbulence model predictions, the current study used an exemplar open CFD test case, the centrifugal compressor ‘Radiver’, to compare the results of three eddy viscosity models and two Reynolds stress type models. The turbulence models investigated in this study were (i) Spalart-Allmaras (SA) model, (ii) the Shear Stress Transport (SST) model, (iii) a modification to the SST model denoted the SST-curvature correction (SST-CC), (iv) Reynolds stress model of Speziale, Sarkar and Gatski (RSM-SSG), and (v) the turbulence frequency formulated Reynolds stress model (RSM-ω). Each was found to be in good agreement with the experiments (below 2% discrepancy), with respect to total-to-total parameters at three different operating conditions. However, for the off-design conditions, local flow field differences were observed between the models, with the SA model showing particularly poor prediction of local flow structures. The SST-CC showed better prediction of curved rotating flows in the impeller. The RSM-ω was better for the wake and separated flow in the diffuser. The SST model showed reasonably stable, robust and time efficient capability to predict global and local flow features.

Dimensionality hyper-reduction and machine learning for dynamical systems with varying parameters

Thesis (Ph.D.)--University of Washington, 2016-08

Um modelo de suporte à comunicação de agentes para tratamento de informação imprecisa baseada em sinônimos

Este trabalho propõe o desenvolvimento de um modelo de suporte á comunicação entre agentes e uma Ontologia com informações imprecisas. Os conceitos desta ontologia podem possuir sinônimos possibilitando a interpretação de termos linguísticos imprecisos. Tal problema é relacionado às questões de desenvolvimento da comunicação em Sistemas Multiagentes, possuindo como referência uma base de conhecimento da qual estes agentes possam requisitar informações. Neste estudo, a premissa do modelo é o de ser útil como componente na utilização por desenvolvedores que queiram utilizar de forma simplificada uma conexão com uma Ontologia para dar suporte na comunicação. Para o presente estudo são discutidos os conceitos sobre a comunicação no ambiente multiagentes. Também é realizada uma revisão sobre o desenvolvimento de Ontologias, de forma a criar uma ontologia para os agentes. A lógica nebulosa, baseado em variáveis linguísticas, servirá como modeladora da imprecisão da informação, dando suporte a essa questão com a Ontologia e a comunicação. De forma a validar o modelo proposto, é realizado um estudo de caso no sistema multiagentes das hortas urbanas do Parque San Jerónimo, de Sevilha, Espanha.

Portuguese children exposure to multiple mycotoxins through food consumption: toward a holistic approach for multiple mycotoxins risk assessment

Humans can be exposed to multiple chemicals at once from a variety of sources, and human risk assessment of multiple chemicals poses several challenges to scientists, risk assessors and risk managers. Ingestion of food is considered a major route of exposure to many contaminants, namely mycotoxins, especially for vulnerable population groups, as children. A lack of sufficient data regarding mycotoxins children risk assessment, could contribute to an inaccuracy of the estimated risk. Efforts must be undertaken to develop initiatives that promote a broad overview of multiple mycotoxins risk assessment. The present work, developed within the MYCOMIX project, aims to assess the risk associated to the exposure of Portuguese children (< 3 years old) to multiple mycotoxins through consumption of foods primarily marketed for this age group. A holistic approach was developed applying deterministic and probabilistic tools to the calculation of mycotoxin daily intake values, integrating children food consumption (3-days food diary), mycotoxins occurrence (HPLC-UV, HPLC-FD, LC-MS/MS and GC-MS), bioaccessibility (standardized in vitro digestion model) and toxicological data (in vitro evaluation of cytotoxicity, genotoxicity and intestinal impact). A case study concerning Portuguese children exposure to patulin (PAT) and ochratoxin A (OTA), two mycotoxins co-occurring in processed cereal-based foods (PCBF) marketed in Portugal, was developed. Main results showed that there is low concern from a public health point of view relatively to PAT and OTA Portuguese children exposure through consumption of PCBF, considering the estimated daily intakes of these two mycotoxins (worst case scenarios, 22.930 ng/kg bw/day and 0.402 ng/kg bw/day, for PAT and OTA, respectively), their bioaccessibility and toxicology results. However, the present case study only concerns the risk associated with the consumption of PCBF and child diet include several other foods. The present work underlines the need to adopt a holistic approach for multiple mycotoxins risk assessment integrating data from exposure, bioacessibility and toxicity domains in order to contribute to a more accurate risk assessment.

AIR SIDE HEAT TRANSFER ENHANCEMENT IN HEAT EXCHANGERS UTILIZING INNOVATIVE DESIGNS AND THE ADDITIVE MANUFACTURING TECHNIQUE

Over the last decade, rapid development of additive manufacturing techniques has allowed the fabrication of innovative and complex designs. One field that can benefit from such technology is heat exchanger fabrication, as heat exchanger design has become more and more complex due to the demand for higher performance particularly on the air side of the heat exchanger. By employing the additive manufacturing, a heat exchanger design was successfully realized, which otherwise would have been very difficult to fabricate using conventional fabrication technologies. In this dissertation, additive manufacturing technique was implemented to fabricate an advanced design which focused on a combination of heat transfer surface and fluid distribution system. Although the application selected in this dissertation is focused on power plant dry cooling applications, the results of this study can directly and indirectly benefit other sectors as well, as the air-side is often the limiting side for in liquid or single phase cooling applications. Two heat exchanger designs were studied. One was an advanced metallic heat exchanger based on manifold-microchannel technology and the other was a polymer heat exchanger based on utilization of prime surface technology. Polymer heat exchangers offer several advantages over metals such as antifouling, anticorrosion, lightweight and often less expensive than comparable metallic heat exchangers. A numerical modeling and optimization were performed to calculate a design that yield an optimum performance. The optimization results show that significant performance enhancement is noted compared to the conventional heat exchangers like wavy fins and plain plate fins. Thereafter, both heat exchangers were scaled down and fabricated using additive manufacturing and experimentally tested. The manifold-micro channel design demonstrated that despite some fabrication inaccuracies, compared to a conventional wavy-fin surface, 15% - 50% increase in heat transfer coefficient was possible for the same pressure drop value. In addition, if the fabrication inaccuracy can be eliminated, an even larger performance enhancement is predicted. Since metal based additive manufacturing is still in the developmental stage, it is anticipated that with further refinement of the manufacturing process in future designs, the fabrication accuracy can be improved. For the polymer heat exchanger, by fabricating a very thin wall heat exchanger (150μm), the wall thermal resistance, which usually becomes the limiting side for polymer heat exchanger, was calculated to account for only up to 3% of the total thermal resistance. A comparison of air-side heat transfer coefficient of the polymer heat exchanger with some of the commercially available plain plate fin surface heat exchangers show that polymer heat exchanger performance is equal or superior to plain plate fin surfaces. This shows the promising potential for polymer heat exchangers to compete with conventional metallic heat exchangers when an additive manufacturing-enabled fabrication is utilized. Major contributions of this study are as follows: (1) For the first time demonstrated the potential of additive manufacturing in metal printing of heat exchangers that benefit from a sophisticated design to yield a performance substantially above the respective conventional systems. Such heat exchangers cannot be fabricated with the conventional fabrication techniques. (2) For the first time demonstrated the potential of additive manufacturing to produce polymer heat exchangers that by design minimize the role of thermal conductivity and deliver a thermal performance equal or better that their respective metallic heat exchangers. In addition of other advantages of polymer over metal like antifouling, anticorrosion, and lightweight. Details of the work are documented in respective chapters of this thesis.

Solid-liquid interactions in microscale structures and devices

Liquid-solid interactions become important as dimensions approach mciro/nano-scale. This dissertation focuses on liquid-solid interactions in two distinct applications: capillary driven self-assembly of thin foils into 3D structures, and droplet wetting of hydrophobic micropatterned surfaces. The phenomenon of self-assembly of complex structures is common in biological systems. Examples include self-assembly of proteins into macromolecular structures and self-assembly of lipid bilayer membranes. The principles governing this phenomenon have been applied to induce self-assembly of millimeter scale Si thin films into spherical and other 3D structures, which are then integrated into light-trapping photovoltaic (PV) devices. Motivated by this application, we present a generalized analytical study of the self-folding of thin plates into deterministic 3D shapes, through fluid-solid interactions, to be used as PV devices. This study consists of developing a model using beam theory, which incorporates the two competing components — a capillary force that promotes folding and the bending rigidity of the foil that resists folding into a 3D structure. Through an equivalence argument of thin foils of different geometry, an effective folding parameter, which uniquely characterizes the driving force for folding, has been identified. A criterion for spontaneous folding of an arbitrarily shaped 2D foil, based on the effective folding parameter, is thus established. Measurements from experiments using different materials and predictions from the model match well, validating the assumptions used in the analysis. As an alternative to the mechanics model approach, the minimization of the total free energy is employed to investigate the interactions between a fluid droplet and a flexible thin film. A 2D energy functional is proposed, comprising the surface energy of the fluid, bending energy of the thin film and gravitational energy of the fluid. Through simulations with Surface Evolver, the shapes of the droplet and the thin film at equilibrium are obtained. A critical thin film length necessary for complete enclosure of the fluid droplet, and hence successful self-assembly into a PV device, is determined and compared with the experimental results and mechanics model predictions. The results from the modeling and energy approaches and the experiments are all consistent. Superhydrophobic surfaces, which have unique properties including self-cleaning and water repelling are desired in many applications. One excellent example in nature is the lotus leaf. To fabricate these surfaces, well designed micro/nano- surface structures are often employed. In this research, we fabricate superhydrophobic micropatterned Polydimethylsiloxane (PDMS) surfaces composed of micropillars of various sizes and arrangements by means of soft lithography. Both anisotropic surfaces, consisting of parallel grooves and cylindrical pillars in rectangular lattices, and isotropic surfaces, consisting of cylindrical pillars in square and hexagonal lattices, are considered. A novel technique is proposed to image the contact line (CL) of the droplet on the hydrophobic surface. This technique provides a new approach to distinguish between partial and complete wetting. The contact area between droplet and microtextured surface is then measured for a droplet in the Cassie state, which is a state of partial wetting. The results show that although the droplet is in the Cassie state, the contact area does not necessarily follow Cassie model predictions. Moreover, the CL is not circular, and is affected by the micropatterns, in both isotropic and anisotropic cases. Thus, it is suggested that along with the contact angle — the typical parameter reported in literature quantifying wetting, the size and shape of the contact area should also be presented. This technique is employed to investigate the evolution of the CL on a hydrophobic micropatterned surface in the cases of: a single droplet impacting the micropatterned surface, two droplets coalescing on micropillars, and a receding droplet resting on the micropatterned surface. Another parameter which quantifies hydrophobicity is the contact angle hysteresis (CAH), which indicates the resistance of the surface to the sliding of a droplet with a given volume. The conventional methods of using advancing and receding angles or tilting stage to measure the resistance of the micropatterned surface are indirect, without mentioning the inaccuracy due to the discrete and stepwise motion of the CL on micropillars. A micronewton force sensor is utilized to directly measure the resisting force by dragging a droplet on a microtextured surface. Together with the proposed imaging technique, the evolution of the CL during sliding is also explored. It is found that, at the onset of sliding, the CL behaves as a linear elastic solid with a constant stiffness. Afterwards, the force first increases and then decreases and reaches a steady state, accompanied with periodic oscillations due to regular pinning and depinning of the CL. Both the maximum and steady state forces are primarily dependent on area fractions of the micropatterned surfaces in our experiment. The resisting force is found to be proportional to the number of pillars which pin the CL at the trailing edge, validating the assumption that the resistance mainly arises from the CL pinning at the trailing edge. In each pinning-and-depinning cycle during the steady state, the CL also shows linear elastic behavior but with a lower stiffness. The force variation and energy dissipation involved can also be determined. This novel method of measuring the resistance of the micropatterned surface elucidates the dependence on CL pinning and provides more insight into the mechanisms of CAH.

Queering religious texts: An exploration of British non-heterosexual Christians’ and Muslims’ strategy of constructing sexuality-affirming hermeneutics.

Religious authority figures often use religious texts as the primary basis for censuring homosexuality. In recent years, however, non-heterosexual Christians and Muslims have begun to contest the discursively produced boundary of sexual morality.Drawing upon two research projects on non-heterosexual Christians and Muslims, this article explores the three approaches embedded in this strategy.While acknowledging that homosexuality is indeed portrayed negatively in some parts of religious texts, the participants critique traditional hermeneutics by highlighting its inaccuracy and socio-cultural specificity, and arguing for a contextualized and culturally relevant interpretation. They also critique the credibility of institutional interpretive authority by highlighting its inadequacy and ideology, and relocating authentic interpretive authority to personal experience. Finally, they recast religious texts to construct resources for their spiritual nourishment.This strategy generally reflects the contemporary western religious landscape that prioritizes the authority of the self over that of religious institution.

Myths and legends: the reality of rape offences reported to a UK police force

Rape myths affect many aspects of the investigative and criminal justice systems. One such myth, the 'real rape' myth, states that most rapes involve a stranger using a weapon attacking a woman violently at night in an isolated, outdoor area, and that women sustain serious injuries from these attacks. The present study examined how often actual offences reported to a central UK police force over a two year period matched the 'real rape' myth. Out of 400 cases of rape reported, not a single incident was found with all the characteristics of the 'real rape' myth. The few stranger rapes that occurred had a strong link to night-time economy activities, such as the victim and offender both having visited pubs, bars, and clubs. By contrast, the majority of reported rape offences (280 cases, 70.7%) were committed by people known to the victim (e.g., domestic and acquaintance rapes), occurred inside a residence, with most victims sustaining no physical injuries from the attack. The benefits of these naturalistic findings from the field for educating people about the inaccuracy of rape myths are discussed.

Explaining engagement in self-monitoring among participants of the DESMOND self-monitoring trial: a qualitative interview study

BACKGROUND: The Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) Self-monitoring Trial reported that people with newly diagnosed type 2 diabetes attending community-based structured education and randomized to self-monitoring of blood glucose (SMBG) or urine monitoring had comparable improvements in biomedical outcomes, but differences in satisfaction with, and continued use of monitoring method, well-being and perceived threat from diabetes. OBJECTIVES: To explore experiences of SMBG and urine monitoring following structured education. We specifically addressed the perceived usefulness of each monitoring method and the associated well-being. METHODS: Qualitative semi-structured interviews with 18 adults with newly diagnosed type 2 diabetes participating in the DESMOND Self-monitoring Trial (SMBG, N=10; urine monitoring, N=8)~12 months into the trial. Analysis was informed by the constant comparative approach. RESULTS: Interviewees reported SMBG as accurate, convenient and useful. Declining use was explained by having established a pattern of managing blood glucose with less frequent monitoring or lack of feedback or encouragement from health care professionals. Many initially positive views of urine monitoring progressively changed due to perceived inaccuracy, leading some to switch to SMBG. Perceiving diabetes as less serious was attributable to lack of symptoms, treatment with diet alone and-in the urine-monitoring group-consistently negative readings. Urine monitoring also provided less visible evidence of diabetes and of the effect of behaviour on glucose. CONCLUSIONS: The findings highlight the importance for professionals of considering patients' preferences when using self-monitoring technologies, including how these change over time, when supporting the self-care behaviours of people with type 2 diabetes.

Feasibility study of a gripper with thermally controlled stiffness of compliant jaws

This paper proposes a simple and compact compliant gripper, whose gripping stiffness can be thermally controlled to accommodate the actuation inaccuracy to avoid or reduce the risk of breaking objects. The principle of reducing jaw stiffness is that thermal change can cause an initial internal compressive force along each compliant beam. A prototype is fabricated with physical testing to verify the feasibility. It has been shown that when a voltage is applied, the gripping stiffness effectively reduces to accommodate more inaccuracy of actuation, which allows delicate or small-scale objects to be gripped.

A probabilistic approach to user mobility prediction for wireless services.

Mobile and wireless networks have long exploited mobility predictions, focused on predicting the future location of given users, to perform more efficient network resource management. In this paper, we present a new approach in which we provide predictions as a probability distribution of the likelihood of moving to a set of future locations. This approach provides wireless services a greater amount of knowledge and enables them to perform more effectively. We present a framework for the evaluation of this new type of predictor, and develop 2 new predictors, HEM and G-Stat. We evaluate our predictors accuracy in predicting future cells for mobile users, using two large geolocation data sets, from MDC [11], [12] and Crawdad [13]. We show that our predictors can successfully predict with as low as an average 2.2% inaccuracy in certain scenarios.

A data dependency based strategy for intermediate data storage in scientific cloud workflow systems

Many scientific workflows are data intensive where large volumes of intermediate data are generated during their execution. Some valuable intermediate data need to be stored for sharing or reuse. Traditionally, they are selectively stored according to the system storage capacity, determined manually. As doing science in the cloud has become popular nowadays, more intermediate data can be stored in scientific cloud workflows based on a pay-for-use model. In this paper, we build an intermediate data dependency graph (IDG) from the data provenance in scientific workflows. With the IDG, deleted intermediate data can be regenerated, and as such we develop a novel intermediate data storage strategy that can reduce the cost of scientific cloud workflow systems by automatically storing appropriate intermediate data sets with one cloud service provider. The strategy has significant research merits, i.e. it achieves a cost-effective trade-off of computation cost and storage cost and is not strongly impacted by the forecasting inaccuracy of data sets' usages. Meanwhile, the strategy also takes the users' tolerance of data accessing delay into consideration. We utilize Amazon's cost model and apply the strategy to general random as well as specific astrophysics pulsar searching scientific workflows for evaluation. The results show that our strategy can reduce the overall cost of scientific cloud workflow execution significantly.