High-Content Analysis of Breast Cancer Using Single-Cell Deep Transfer Learning

High-content analysis has revolutionized cancer drug discovery by identifying substances that alter the phenotype of a cell, which prevents tumor growth and metastasis. The high-resolution biofluorescence images from assays allow precise quantitative measures enabling the distinction of small molecules of a host cell from a tumor. In this work, we are particularly interested in the application of deep neural networks (DNNs), a cutting-edge machine learning method, to the classification of compounds in chemical mechanisms of action (MOAs). Compound classification has been performed using image-based profiling methods sometimes combined with feature reduction methods such as principal component analysis or factor analysis. In this article, we map the input features of each cell to a particular MOA class without using any treatment-level profiles or feature reduction methods. To the best of our knowledge, this is the first application of DNN in this domain, leveraging single-cell information. Furthermore, we use deep transfer learning (DTL) to alleviate the intensive and computational demanding effort of searching the huge parameter's space of a DNN. Results show that using this approach, we obtain a 30% speedup and a 2% accuracy improvement.

Single-function approach to calibrating whatman n.º 42 filter paper based on suction versus water content relationships

Several suction–water-content (s-w) calibrations for the filter paper method (FPM) used for soil-suction measurement have been published. Most of the calibrations involve a bilinear function (i.e., two different equations) with an inflection point occurring at 60 kPacontent range of 30 %

Correlations Between the Collagen Content of the Human Left Ventricular Myocardium, Measured by Biochemical and Morphometric Methods

OBJECTIVE: To assess, in myocardium specimens obtained from necropsies, the correlation between the concentration of hydroxyproline, measured with the photocolorimetric method, and the intensity of fibrosis, determined with the morphometric method. METHODS: Left ventricle myocardium samples were obtained from 45 patients who had undergone necropsy, some of them with a variety of cardiopathies and others without any heart disease. The concentrations of hydroxyproline were determined with the photocolorimetric method. In the histologic sections from each heart, the myocardial fibrosis was quantified by using a light microscope with an integrating ocular lens. RESULTS: A median of, respectively, 4.5 and 4.3 mug of hydroxyproline/mg of dry weight was found in fixed and nonfixed left ventricle myocardium fragments. A positive correlation occurred between the hydroxyproline concentrations and the intensity of fibrosis, both in the fixed (Sr=+0.25; p=0.099) and in the nonfixed (Sr=+0.32; p=0.03) specimens. CONCLUSION: The biochemical methodology was proven to be adequate, and manual morphometry was shown to have limitations that may interfere with the statistical significance of correlations for the estimate of fibrosis intensity in the human myocardium.

The ribonucleic acid content of some mammalian erythrocytes

RNA was determined in red blood cells of man and other mammals. Our report is based on 41 determinations. Red blood cells of rat showed the highest values in comparison with the blood cells of guinea pig, rabbit, horse and sheep which showed the lowest values, and man with intermediate ones. The method used was a combination of Schimidt and Thanhauser and Schneider extractions with the final reactions of pentose with the orcinol reagent colorimetrically measured.

Lowering blood alcohol content levels to save lives: The european experience

Road safety has become an increasing concern in developed countries due to the significant amount of mortal victims and the economic losses derived. Only in 2005 these losses rose to 200.000 million euros, a significant amount - approximately the 2% of its GDP- that easily justifies any public intervention. One tool used by governments to face this challenge is the enactment of stricter policies and regulations. Since drunk driving is one of the most important concerns of public authorities on this field, several European countries decided to lower their illegal Blood Alcohol Content levels to 0.5 mg/ml during the last decade. This study evaluates for the first time the effectiveness of this transition using European panel-based data (CARE) for the period 1991-2003 using the Differences-in-Differences method in a fixed effects estimation that allows for any pattern of correlation (Cluster-Robust). My results show the existence of positive impacts on certain groups of road users and for the whole population when the policy is accompanied by some enforcement interventions. Moreover, a time lag of more than two years is found in that effectiveness. Finally, I also assert the importance of controlling for serial correlation in the evaluation of this kind of policies.

An interregional input-output analysis of the pollution content of trade flows and environmental trade balances between five states in the US Mid-West

In this paper we attempt an empirical application of the multi-region input-output (MRIO) method in order to enumerate the pollution content of interregional trade flows between five Mid-West regions/states in the US –Illinois, Indiana, Iowa, Michigan and Wisconsin – and the rest of the US. This allows us to analyse some very important issues in terms of the nature and significance of interregional environmental spillovers within the US Mid-West and the existence of pollution ‘trade balances’ between states. Our results raise questions in terms of the extent to which authorities at State level can control local emissions where they are limited in the way some emissions can be controlled, particularly with respect to changes in demand elsewhere in the Mid-West and US. This implies a need for policy co-ordination between national and state level authorities in the US to meet emissions reductions targets. The existence of an environmental trade balances between states also raises issues in terms of net losses/gains in terms of pollutants as a result of interregional trade within the US and whether, if certain activities can be carried out using less polluting technology in one region relative to others, it is better for the US as a whole if this type of relationship exists.

Intergenerational Mobility and the Informative Content of Surnames

We propose a new methodology for measuring intergenerational mobility in economic wellbeing. Our method is based on the joint distribution of surnames and economic outcomes. It circumvents the need for intergenerational panel data, a long-standing stumbling block for understanding mobility. A single cross-sectional dataset is su cient. Our main idea is simple. If `inheritance' is important for economic outcomes, then rare surnames should predict economic outcomes in the cross-section. This is because rare surnames are indicative of familial linkages. Of course, if the number of rare surnames is small, this won't work. But rare surnames are abundant in the highly-skewed nature of surname distributions from most Western societies. We develop a model that articulates this idea and shows that the more important is inheritance, the more informative will be surnames. This result is robust to a variety of di erent assumptions about fertility and mating. We apply our method using the 2001 census from Catalonia, a large region of Spain. We use educational attainment as a proxy for overall economic well-being. Our main nding is that mobility has decreased among the di erent generations of the 20th century. A complementary analysis based on sibling correlations con rms our results and provides a robustness check on our method. Our model and our data allow us to examine one possible explanation for the observed decrease in mobility. We nd that the degree of assortative mating has increased over time. Overall, we argue that our method has promise because it can tap the vast mines of census data that are available in a heretofore unexploited manner.

Analysis of a finite volume element method for the Stokes problem

In this paper we propose a stabilized conforming finite volume element method for the Stokes equations. On stating the convergence of the method, optimal a priori error estimates in different norms are obtained by establishing the adequate connection between the finite volume and stabilized finite element formulations. A superconvergence result is also derived by using a postprocessing projection method. In particular, the stabilization of the continuous lowest equal order pair finite volume element discretization is achieved by enriching the velocity space with local functions that do not necessarily vanish on the element boundaries. Finally, some numerical experiments that confirm the predicted behavior of the method are provided.

The serine repeat antigen (SERA) gene family phylogeny in Plasmodium: the impact of GC content and reconciliation of gene and species trees.

Plasmodium falciparum is the parasite responsible for the most acute form of malaria in humans. Recently, the serine repeat antigen (SERA) in P. falciparum has attracted attention as a potential vaccine and drug target, and it has been shown to be a member of a large gene family. To clarify the relationships among the numerous P. falciparum SERAs and to identify orthologs to SERA5 and SERA6 in Plasmodium species affecting rodents, gene trees were inferred from nucleotide and amino acid sequence data for 33 putative SERA homologs in seven different species. (A distance method for nucleotide sequences that is specifically designed to accommodate differing GC content yielded results that were largely compatible with the amino acid tree. Standard-distance and maximum-likelihood methods for nucleotide sequences, on the other hand, yielded gene trees that differed in important respects.) To infer the pattern of duplication, speciation, and gene loss events in the SERA gene family history, the resulting gene trees were then "reconciled" with two competing Plasmodium species tree topologies that have been identified by previous phylogenetic studies. Parsimony of reconciliation was used as a criterion for selecting a gene tree/species tree pair and provided (1) support for one of the two species trees and for the core topology of the amino acid-derived gene tree, (2) a basis for critiquing fine detail in a poorly resolved region of the gene tree, (3) a set of predicted "missing genes" in some species, (4) clarification of the relationship among the P. falciparum SERA, and (5) some information about SERA5 and SERA6 orthologs in the rodent malaria parasites. Parsimony of reconciliation and a second criterion--implied mutational pattern at two key active sites in the SERA proteins-were also seen to be useful supplements to standard "bootstrap" analysis for inferred topologies.

Estimation of the lateral correlation structure of subsurface water content from surface-based ground-penetrating radar reflection images

Over the past decade, significant interest has been expressed in relating the spatial statistics of surface-based reflection ground-penetrating radar (GPR) data to those of the imaged subsurface volume. A primary motivation for this work is that changes in the radar wave velocity, which largely control the character of the observed data, are expected to be related to corresponding changes in subsurface water content. Although previous work has indeed indicated that the spatial statistics of GPR images are linked to those of the water content distribution of the probed region, a viable method for quantitatively analyzing the GPR data and solving the corresponding inverse problem has not yet been presented. Here we address this issue by first deriving a relationship between the 2-D autocorrelation of a water content distribution and that of the corresponding GPR reflection image. We then show how a Bayesian inversion strategy based on Markov chain Monte Carlo sampling can be used to estimate the posterior distribution of subsurface correlation model parameters that are consistent with the GPR data. Our results indicate that if the underlying assumptions are valid and we possess adequate prior knowledge regarding the water content distribution, in particular its vertical variability, this methodology allows not only for the reliable recovery of lateral correlation model parameters but also for estimates of parameter uncertainties. In the case where prior knowledge regarding the vertical variability of water content is not available, the results show that the methodology still reliably recovers the aspect ratio of the heterogeneity.

Evaluation of email alerts in practice: Part 2. Validation of the information assessment method.

RATIONALE AND OBJECTIVE:. The information assessment method (IAM) permits health professionals to systematically document the relevance, cognitive impact, use and health outcomes of information objects delivered by or retrieved from electronic knowledge resources. The companion review paper (Part 1) critically examined the literature, and proposed a 'Push-Pull-Acquisition-Cognition-Application' evaluation framework, which is operationalized by IAM. The purpose of the present paper (Part 2) is to examine the content validity of the IAM cognitive checklist when linked to email alerts. METHODS: A qualitative component of a mixed methods study was conducted with 46 doctors reading and rating research-based synopses sent on email. The unit of analysis was a doctor's explanation of a rating of one item regarding one synopsis. Interviews with participants provided 253 units that were analysed to assess concordance with item definitions. RESULTS AND CONCLUSION: The content relevance of seven items was supported. For three items, revisions were needed. Interviews suggested one new item. This study has yielded a 2008 version of IAM.

Biochemical, morphological and content characterization of synaptobrevin 2-expressing vesicles in astrocytes

Neuron-astrocyte reciprocal communication at synapses has emerged as a novel signalling pathway in brain function. Astrocytes sense the level of synaptic activity and, in turn, influence its efficacy through the regulated release of ''glio- transmitters'' such as glutamate, ATP or D-serine. A calcium- dependent exocytosis is proposed to drive the release of gliotransmitters but its existence is still debated. To shed light onto the mechanisms controlling the storage and the release of gliotransmitters and namely D-serine, we have developed a new method for the immunoisolation of synaptobrevin 2-positive vesicles from rat cortical astrocytes in culture. The purified organelles are clear round shape vesicles of excellent purity as judged by electron microscopy. Immunoblotting analysis revealed that isolated vesicles contain most of the major proteins already described for neuron-derived vesicles. In addition, we have analyzed the content for various amino acids of these vesicles by means of chiral capillary electro- phoresis coupled to laser-induced fluorescence detection and liquid chromatography coupled to mass spectrometry. Post- embedding immunogold labelling of the rat neocortex and hippocampus further revealed the expression of D-serine and glutamate in astrocyte processes contacting excitatory sy- napses. Our results provide significant support for the existence of secretory glial vesicles storing chemical substances like D- serine and glutamate and thus point to the co-release of amino acids by exocytosis in astrocytes.

Instrument for assessing the quality of mobile emergency pre-hospital care: content validation

OBJECTIVES To validate an instrument to assess quality of mobile emergency pre-hospital care. METHOD A methodological study where 20 professionals gave their opinions on the items of the proposed instrument. The analysis was performed using Kappa test (K) and Content Validity Index (CVI), considering K> 0.80 and CVI ≥ 0.80. RESULTS Three items were excluded from the instrument: Professional Compensation; Job Satisfaction and Services Performed. Items that obtained adequate K and CVI indexes and remained in the instrument were: ambulance conservation status; physical structure; comfort in the ambulance; availability of material resources; user/staff safety; continuous learning; safety demonstrated by the team; access; welcoming; humanization; response time; costumer privacy; guidelines on care; relationship between professionals and costumers; opportunity for costumers to make complaints and multiprofessional conjunction/actuation. CONCLUSION The instrument to assess quality of care has been validated and may contribute to the evaluation of pre-hospital care in mobile emergency services.

Intergenerational mobility and the informative content of surnames

We propose an alternative method for measuring intergenerational mobility. Measurements obtained fromtraditional methods (based on panel data) are scarce, difficult to compare across countries and almost impossible to get across time. In particular, this means that we do not know how intergenerational mobility is correlated with growth, income or the degree of inequality.Our proposal is to measure the informative content of surnames in one census. The more information thesurname has on the income of an individual, the more important is her background in determining her outcomes; and thus, the less mobility there is.The reason is that surnames provide information about family relationships because the distribution ofsurnames is necessarily very skewed. A large percentage of the population is bound to have a very unfrequent surname. For them the partition generated by surnames is very informative on family linkages.First, we develop a model whose endogenous variable is the joint distribution of surnames and income.There, we explore the relationship between mobility and the informative content of surnames. We allow for assortative mating to be a determinant of both.Second, we use our methodology to show that in large Spanish region the informative content of surnamesis large and consistent with the model. We also show that it has increased over time, indicating a substantial drop in the degree of mobility. Finally, using the peculiarities of the Spanish surname convention we show that the degree of assortative mating has also increased over time, in such a manner that might explain the decrease in mobility observed.Our method allows us to provide measures of mobility comparable across time. It should also allow us tostudy other issues related to inheritance.

Sampling and TDR probe insertion in the determination of the volumetric soil water content

Volumetric soil water content (theta) can be evaluated in the field by direct or indirect methods. Among the direct, the gravimetric method is regarded as highly reliable and thus often preferred. Its main disadvantages are that sampling and laboratory procedures are labor intensive, and that the method is destructive, which makes resampling of a same point impossible. Recently, the time domain reflectometry (TDR) technique has become a widely used indirect, non-destructive method to evaluate theta. In this study, evaluations of the apparent dielectric number of soils (epsilon) and samplings for the gravimetrical determination of the volumetric soil water content (thetaGrav) were carried out at four sites of a Xanthic Ferralsol in Manaus - Brazil. With the obtained epsilon values, theta was estimated using empirical equations (thetaTDR), and compared with thetaGrav derived from disturbed and undisturbed samples. The main objective of this study was the comparison of thetaTDR estimates of horizontally as well as vertically inserted probes with the thetaGrav values determined by disturbed and undisturbed samples. Results showed that thetaTDR estimates of vertically inserted probes and the average of horizontally measured layers were only slightly and insignificantly different. However, significant differences were found between the thetaTDR estimates of different equations and between disturbed and undisturbed samples in the thetaGrav determinations. The use of the theoretical Knight et al. model, which permits an evaluation of the soil volume assessed by TDR probes, is also discussed. It was concluded that the TDR technique, when properly calibrated, permits in situ, nondestructive measurements of q in Xanthic Ferralsols of similar accuracy as the gravimetric method.