On the anharmonic, multi-phonon, Debye-Waller contributions to the phonon-limited resistivity of metals : applications to Na and K

The anharmonic, multi-phonon (MP), and Oebye-Waller factor (OW) contributions to the phonon limited resistivity (;0) of metals derived by Shukla and Muller (1979) by the doubletime temperature dependent Green function method have been numerically evaluated for Na and K in the high temperature limit. The anharmonic contributions arise from the cubic and quartic shift of phonons (CS, QS), and phonon width (W) and the interference term (1). The QS, MP and OW contributions to I' are also derived by the matrix element method and the results are in agreement with those of Shukla and Muller (1979). In the high temperature limit, the contributions to;O from each of the above mentioned terms are of the type BT2 For numerical calculations suitable expressions are derived for the anharmonic contributions to ~ in terms of the third and fourth rank tensors obtained by the Ewald procedure. The numerical calculation of the contributions to;O from the OW, MP term and the QS have been done exactly and from the CS, Wand I terms only approximately in the partial and total Einstein approximations (PEA, TEA), using a first principle approach (Shukla and Taylor (1976)). The results obtained indicate that there is a strong pairwise cancellation between the: OW and MP terms, the QS and CS and the Wand I terms. The sum total of these contributions to;O for Na and K amounts to 4 to 11% and 2 to 7%, respectively, in the PEA while in the TEA they amount to 3 to 7% and 1 to 4%, respectively, in the temperature range.

Ventilation-perfusion ratio in perflubron during partial liquid ventilation

BACKGROUND: Functional magnetic resonance imaging (fMRI) of fluorine-19 allows for the mapping of oxygen partial pressure within perfluorocarbons in the alveolar space (Pao(2)). Theoretically, fMRI-detected Pao(2) can be combined with the Fick principle approach, i.e., a mass balance of oxygen uptake by ventilation and delivery by perfusion, to quantify the ventilation-perfusion ratio (Va/Q) of a lung region: The mixed venous blood and the inspiratory oxygen fraction, which are equal for all lung regions, are measured. In addition, the local expiratory oxygen fraction and the end capillary oxygen content, both of which may differ between the lung regions, are calculated using the fMRI-detected Pao(2). We investigated this approach by numerical simulations and applied it to quantify local Va/Q in the perfluorocarbons during partial liquid ventilation. METHODS: Numerical simulations were performed to analyze the sensitivity of the Va/Q calculation and to compare this approach with another one proposed by Rizi et al. in 2004 (Magn Reson Med 2004;52:65-72). Experimentally, the method was used during partial liquid ventilation in 7 anesthetized pigs. The Pao(2) distribution in intraalveolar perflubron was measured by fluorine-19 MRI. Respiratory gas fractions together with arterial and mixed venous blood samples were taken to quantify oxygen partial pressure and content. Using the Fick principle, the local Va/Q was estimated. The impact of gravity (nondependent versus dependent) of perflubron dose (10 vs 20 mL/kg body weight) and of inspired oxygen fraction (Fio(2)) (0.4-1.0) on Va/Q was examined. RESULTS: In numerical simulations, the Fick principle proved to be appropriate over the Va/Q range from 0.02 to 2.5. Va/Q values were in acceptable agreement with the method published by Rizi et al. In the experimental setting, low mean Va/Q values were found in perflubron (confidence interval [CI] 0.08-0.29 with 20 mL/kg perflubron). At this dose, Va/Q in the nondependent lung was higher (CI 0.18-0.39) than in the dependent lung regions (CI 0.06-0.16; P = 0.006; Student t test). Differences depending on Fio(2) or perflubron dose were, however, small. CONCLUSION: The results show that derivation of Va/Q from local Po(2) measurements using fMRI in perflubron is feasible. The low detected Va/Q suggests that oxygen transport into the perflubron-filled alveolar space is significantly restrained.

Predictive oncology: a review of multidisciplinary, multiscale in silico modeling linking phenotype, morphology and growth.

Empirical evidence and theoretical studies suggest that the phenotype, i.e., cellular- and molecular-scale dynamics, including proliferation rate and adhesiveness due to microenvironmental factors and gene expression that govern tumor growth and invasiveness, also determine gross tumor-scale morphology. It has been difficult to quantify the relative effect of these links on disease progression and prognosis using conventional clinical and experimental methods and observables. As a result, successful individualized treatment of highly malignant and invasive cancers, such as glioblastoma, via surgical resection and chemotherapy cannot be offered and outcomes are generally poor. What is needed is a deterministic, quantifiable method to enable understanding of the connections between phenotype and tumor morphology. Here, we critically assess advantages and disadvantages of recent computational modeling efforts (e.g., continuum, discrete, and cellular automata models) that have pursued this understanding. Based on this assessment, we review a multiscale, i.e., from the molecular to the gross tumor scale, mathematical and computational "first-principle" approach based on mass conservation and other physical laws, such as employed in reaction-diffusion systems. Model variables describe known characteristics of tumor behavior, and parameters and functional relationships across scales are informed from in vitro, in vivo and ex vivo biology. We review the feasibility of this methodology that, once coupled to tumor imaging and tumor biopsy or cell culture data, should enable prediction of tumor growth and therapy outcome through quantification of the relation between the underlying dynamics and morphological characteristics. In particular, morphologic stability analysis of this mathematical model reveals that tumor cell patterning at the tumor-host interface is regulated by cell proliferation, adhesion and other phenotypic characteristics: histopathology information of tumor boundary can be inputted to the mathematical model and used as a phenotype-diagnostic tool to predict collective and individual tumor cell invasion of surrounding tissue. This approach further provides a means to deterministically test effects of novel and hypothetical therapy strategies on tumor behavior.

Toward Never-Ending Object Learning for Robots

Thesis (Ph.D.)--University of Washington, 2016-06

A novel in vitro metabolomics approach for neurotoxicity testing, proof of principle for methyl mercury chloride and caffeine

There is a need for more efficient methods giving insight into the complex mechanisms of neurotoxicity. Testing strategies including in vitro methods have been proposed to comply with this requirement. With the present study we aimed to develop a novel in vitro approach which mimics in vivo complexity, detects neurotoxicity comprehensively, and provides mechanistic insight. For this purpose we combined rat primary re-aggregating brain cell cultures with a mass spectrometry (MS)-based metabolomics approach. For the proof of principle we treated developing re-aggregating brain cell cultures for 48h with the neurotoxicant methyl mercury chloride (0.1-100muM) and the brain stimulant caffeine (1-100muM) and acquired cellular metabolic profiles. To detect toxicant-induced metabolic alterations the profiles were analysed using commercial software which revealed patterns in the multi-parametric dataset by principal component analyses (PCA), and recognised the most significantly altered metabolites. PCA revealed concentration-dependent cluster formations for methyl mercury chloride (0.1-1muM), and treatment-dependent cluster formations for caffeine (1-100muM) at sub-cytotoxic concentrations. Four relevant metabolites responsible for the concentration-dependent alterations following methyl mercury chloride treatment could be identified using MS-MS fragmentation analysis. These were gamma-aminobutyric acid, choline, glutamine, creatine and spermine. Their respective mass ion intensities demonstrated metabolic alterations in line with the literature and suggest that the metabolites could be biomarkers for mechanisms of neurotoxicity or neuroprotection. In addition, we evaluated whether the approach could identify neurotoxic potential by testing eight compounds which have target organ toxicity in the liver, kidney or brain at sub-cytotoxic concentrations. PCA revealed cluster formations largely dependent on target organ toxicity indicating possible potential for the development of a neurotoxicity prediction model. With such results it could be useful to perform a validation study to determine the reliability, relevance and applicability of this approach to neurotoxicity screening. Thus, for the first time we show the benefits and utility of in vitro metabolomics to comprehensively detect neurotoxicity and to discover new biomarkers.

UNITRAN: A Principle-Based Approach to Machine Translation

Machine translation has been a particularly difficult problem in the area of Natural Language Processing for over two decades. Early approaches to translation failed since interaction effects of complex phenomena in part made translation appear to be unmanageable. Later approaches to the problem have succeeded (although only bilingually), but are based on many language-specific rules of a context-free nature. This report presents an alternative approach to natural language translation that relies on principle-based descriptions of grammar rather than rule-oriented descriptions. The model that has been constructed is based on abstract principles as developed by Chomsky (1981) and several other researchers working within the "Government and Binding" (GB) framework. Thus, the grammar is viewed as a modular system of principles rather than a large set of ad hoc language-specific rules.

Transcranial magnetic stimulation in mild to severe hemiparesis early after stroke: a proof of principle and novel approach to improve motor function

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can enhance function of the paretic hand in patients with mild motor impairment. Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown. In this pilot, randomized, double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpatient customary rehabilitation, in 30 patients within 5-45 days after ischemic stroke, and mild to severe hand paresis. The primary feasibility outcome was compliance with the interventions. The primary safety outcome was the proportion of intervention-related adverse events. Performance of the paretic hand in the Jebsen-Taylor test and pinch strength were secondary outcomes. Outcomes were assessed at baseline, after ten sessions of treatment administered over 2 weeks and at 1 month after end of treatment. Baseline clinical features were comparable across groups. For the primary feasibility outcome, compliance with treatment was 100% in the active group and 94% in the sham group. There were no serious intervention-related adverse events. There were significant improvements in performance in the Jebsen-Taylor test (mean, 12.3% 1 month after treatment) and pinch force (mean, 0.5 Newtons) in the active group, but not in the sham group. Low-frequency rTMS to the contralesional motor cortex early after stroke is feasible, safe and potentially effective to improve function of the paretic hand, in patients with mild to severe hemiparesis. These promising results will be valuable to design larger randomized clinical trials.

Constraint-force-based approach of modelling compliant mechanisms: principle and application

Numerous works have been conducted on modelling basic compliant elements such as wire beams, and closed-form analytical models of most basic compliant elements have been well developed. However, the modelling of complex compliant mechanisms is still a challenging work. This paper proposes a constraint-force-based (CFB) modelling approach to model compliant mechanisms with a particular emphasis on modelling complex compliant mechanisms. The proposed CFB modelling approach can be regarded as an improved free-body- diagram (FBD) based modelling approach, and can be extended to a development of the screw-theory-based design approach. A compliant mechanism can be decomposed into rigid stages and compliant modules. A compliant module can offer elastic forces due to its deformation. Such elastic forces are regarded as variable constraint forces in the CFB modelling approach. Additionally, the CFB modelling approach defines external forces applied on a compliant mechanism as constant constraint forces. If a compliant mechanism is at static equilibrium, all the rigid stages are also at static equilibrium under the influence of the variable and constant constraint forces. Therefore, the constraint force equilibrium equations for all the rigid stages can be obtained, and the analytical model of the compliant mechanism can be derived based on the constraint force equilibrium equations. The CFB modelling approach can model a compliant mechanism linearly and nonlinearly, can obtain displacements of any points of the rigid stages, and allows external forces to be exerted on any positions of the rigid stages. Compared with the FBD based modelling approach, the CFB modelling approach does not need to identify the possible deformed configuration of a complex compliant mechanism to obtain the geometric compatibility conditions and the force equilibrium equations. Additionally, the mathematical expressions in the CFB approach have an easily understood physical meaning. Using the CFB modelling approach, the variable constraint forces of three compliant modules, a wire beam, a four-beam compliant module and an eight-beam compliant module, have been derived in this paper. Based on these variable constraint forces, the linear and non-linear models of a decoupled XYZ compliant parallel mechanism are derived, and verified by FEA simulations and experimental tests.

Multiobjective Particle Swarm Approach for the Design of a Brushless DC Wheel Motor

The roots of swarm intelligence are deeply embedded in the biological study of self-organized behaviors in social insects. Particle swarm optimization (PSO) is one of the modern metaheuristics of swarm intelligence, which can be effectively used to solve nonlinear and non-continuous optimization problems. The basic principle of PSO algorithm is formed on the assumption that potential solutions (particles) will be flown through hyperspace with acceleration towards more optimum solutions. Each particle adjusts its flying according to the flying experiences of both itself and its companions using equations of position and velocity. During the process, the coordinates in hyperspace associated with its previous best fitness solution and the overall best value attained so far by other particles within the group are kept track and recorded in the memory. In recent years, PSO approaches have been successfully implemented to different problem domains with multiple objectives. In this paper, a multiobjective PSO approach, based on concepts of Pareto optimality, dominance, archiving external with elite particles and truncated Cauchy distribution, is proposed and applied in the design with the constraints presence of a brushless DC (Direct Current) wheel motor. Promising results in terms of convergence and spacing performance metrics indicate that the proposed multiobjective PSO scheme is capable of producing good solutions.

A geometrical approach of 3-D FEA for educational purposes applied to electrostatic fields

A geometrical approach of the finite-element analysis applied to electrostatic fields is presented. This approach is particularly well adapted to teaching Finite Elements in Electrical Engineering courses at undergraduate level. The procedure leads to the same system of algebraic equations as that derived by classical approaches, such as variational principle or weighted residuals for nodal elements with plane symmetry. It is shown that the extension of the original procedure to three dimensions is straightforward, provided the domain be meshed in first-order tetrahedral elements. The element matrices are derived by applying Maxwell`s equations in integral form to suitably chosen surfaces in the finite-element mesh.

Time course proteomic profiling of human myocardial infarction plasma samples: An approach to new biomarker discovery

Background: The aim of this study was to identify novel candidate biomarker proteins differentially expressed in the plasma of patients with early stage acute myocardial infarction (AMI) using SELDI-TOF-MS as a high throughput screening technology. Methods: Ten individuals with recent acute ischemic-type chest pain (< 12 h duration) and ST-segment elevation AMI (1STEMI) and after a second AMI (2STEMI) were selected. Blood samples were drawn at six times after STEMI diagnosis. The first stage (T(0)) was in Emergency Unit before receiving any medication, the second was just after primary angioplasty (T(2)), and the next four stages occurred at 12 h intervals after T(0). Individuals (n = 7) with similar risk factors for cardiovascular disease and normal ergometric test were selected as a control group (CG). Plasma proteomic profiling analysis was performed using the top-down (i.e. intact proteins) SELDI-TOF-MS, after processing in a Multiple Affinity Removal Spin Cartridge System (Agilent). Results: Compared with the CG, the 1STEMI group exhibited 510 differentially expressed protein peaks in the first 48 h after the AMI (p < 0.05). The 2STEMI group, had similar to 85% fewer differently expressed protein peaks than those without previous history of AMI (76, p < 0.05). Among the 16 differentially-regulated protein peaks common to both STEMI cohorts (compared with the CG at T(0)), 6 peaks were persistently down-regulated at more than one time-stage, and also were inversed correlated with serum protein markers (cTnI, CK and CKMB) during 48 h-period after IAM. Conclusions: Proteomic analysis by SELDI-TOF-MS technology combined with bioinformatics tools demonstrated differential expression during a 48 h time course suggests a potential role of some of these proteins as biomarkers for the very early stages of AMI, as well as for monitoring early cardiac ischemic recovery. (C) 2011 Elsevier B.V. All rights reserved.

Population health diagnosis with an ecohealth approach

OBJECTIVE To analyze the characteristics of health diagnosis according to the ecohealth approach in rural and urban communities in Mexico.METHODS Health diagnosis were conducted in La Nopalera, from December 2007 to October 2008, and in Atlihuayan, from December 2010 to October 2011. The research was based on three principles of the ecohealth approach: transdisciplinarity, community participation, gender and equity. To collect information, a joint methodology and several techniques were used to stimulate the participation of inhabitants. The diagnostic exercise was carried out in five phases that went from collecting information to prioritization of problems.RESULTS The constitution of the transdisciplinary team, as well as the participation of the population and the principle of gender/equity were differentials between the communities. In the rural community, the active participation of inhabitants and authorities was achieved and the principles of transdisciplinarity and gender/equity were incorporated.CONCLUSIONS With all the difficulties that entails the boost in participation, the incorporation of gender/equity and transdisciplinarity in health diagnosis allowed a holistic public health approach closer to the needs of the population.

Development of principle culture medium formulations for Saccharomyces cerevisiae

Saccharomyces cerevisiae as well as other microorganisms are frequently used in industry with the purpose of obtain different kind of products that can be applied in several areas (research investigation, pharmaceutical compounds, etc.). In order to obtain high yields for the desired product, it is necessary to make an adequate medium supplementation during the growth of the microorganisms. The higher yields are typically reached by using complex media, however the exact formulation of these media is not known. Moreover, it is difficult to control the exact composition of complex media, leading to batch-to-batch variations. So, to overcome this problem, some industries choose to use defined media, with a defined and known chemical composition. However these kind of media, many times, do not reach the same high yields that are obtained by using complex media. In order to obtain similar yield with defined media the addition of many different compounds has to be tested experimentally. Therefore, the industries use a set of empirical methods with which it is tried to formulate defined media that can reach the same high yields as complex media. In this thesis, a defined medium for Saccharomyces cerevisiae was developed using a rational design approach. In this approach a given metabolic network of Saccharomyces cerevisiae is divided into a several unique and not further decomposable sub networks of metabolic reactions that work coherently in steady state, so called elementary flux modes. The EFMtool algorithm was used in order to calculate the EFM’s for two Saccharomyces cerevisiae metabolic networks (amino acids supplemented metabolic network; amino acids non-supplemented metabolic network). For the supplemented metabolic network 1352172 EFM’s were calculated and then divided into: 1306854 EFM’s producing biomass, and 18582 EFM’s exclusively producing CO2 (cellular respiration). For the non-supplemented network 635 EFM’s were calculated and then divided into: 215 EFM’s producing biomass; 420 EFM’s producing exclusively CO2. The EFM’s of each group were normalized by the respective glucose consumption value. After that, the EFMs’ of the supplemented network were grouped again into: 30 clusters for the 1306854 EFMs producing biomass and, 20 clusters for the 18582 EFM’s producing CO2. For the non-supplemented metabolic network the respective EFM’s of each metabolic function were grouped into 10 clusters. After the clustering step, the concentrations of the other medium compounds were calculated by considering a reasonable glucose amount and by accounting for the proportionality between the compounds concentrations and the glucose ratios. The approach adopted/developed in this thesis may allow a faster and more economical way for media development.

The system-wide impacts of the external benefits to higher education on the Scottish economy: An exploratory “micro-to-macro” approach

The private market benefits of education, i.e. the wage premia of graduates, are widely studied at the micro level, although the magnitude of their macroeconomic impact is disputed. However, there are additional benefits of education, which are less well understood but could potentially drive significant macroeconomic impacts. Following the taxonomy of McMahon (2009) we identify four different types of benefits of education. These are: private market benefits (wage premia); private non market benefits (own health, happiness, etc.); external market benefits (productivity spillovers; and external non-market benefits (crime rates, civic society, democratisation, etc.). Drawing on available microeconometric evidence we use a micro-to-macro simulation approach (Hermannsson et al, 2010) to estimate the macroeconomic impacts of external benefits of higher education. We explore four cases: technology spillovers from HEIs; productivity spillovers from more skilled workers in the labour market; reduction in property crime; and the potential overall impact of external and private non-market benefits. Our results suggest that the external economic benefits of higher education could potentially be very large. However, given the dearth of microeconomic evidence this result should be seen as tentative. Our aim is to illustrate the links from education to the wider economy in principle and encourage further research in the field.

Identifying genetic signatures of selection in a non-model species, alpine gentian (Gentiana nivalis L.), using a landscape genetic approach

It is generally accepted that most plant populations are locally adapted. Yet, understanding how environmental forces give rise to adaptive genetic variation is a challenge in conservation genetics and crucial to the preservation of species under rapidly changing climatic conditions. Environmental variation, phylogeographic history, and population demographic processes all contribute to spatially structured genetic variation, however few current models attempt to separate these confounding effects. To illustrate the benefits of using a spatially-explicit model for identifying potentially adaptive loci, we compared outlier locus detection methods with a recently-developed landscape genetic approach. We analyzed 157 loci from samples of the alpine herb Gentiana nivalis collected across the European Alps. Principle coordinates of neighbor matrices (PCNM), eigenvectors that quantify multi-scale spatial variation present in a data set, were incorporated into a landscape genetic approach relating AFLP frequencies with 23 environmental variables. Four major findings emerged. 1) Fifteen loci were significantly correlated with at least one predictor variable (R (adj) (2) > 0.5). 2) Models including PCNM variables identified eight more potentially adaptive loci than models run without spatial variables. 3) When compared to outlier detection methods, the landscape genetic approach detected four of the same loci plus 11 additional loci. 4) Temperature, precipitation, and solar radiation were the three major environmental factors driving potentially adaptive genetic variation in G. nivalis. Techniques presented in this paper offer an efficient method for identifying potentially adaptive genetic variation and associated environmental forces of selection, providing an important step forward for the conservation of non-model species under global change.