Parameterization of written signatures based on EFD

In this work we propose a method to quantify written signatures from digitalized images based on the use of Elliptical Fourier Descriptors (EFD). As usually signatures are not represented as a closed contour, and being that a necessary condition in order to apply EFD, we have developed a method that represents the signatures by means of a set of closed contours. One of the advantages of this method is that it can reconstruct the original shape from all the coefficients, or an approximated shape from a reduced set of them finding the appropriate number of EFD coefficients required for preserving the important information in each application. EFD provides accurate frequency information, thus the use of EFD opens many possibilities. The method can be extended to represent other kind of shapes.

Sentence des juge et consuls de Paris ; qui condamne à payer deux lettres de change adhirées, quoiqu'elles ne soient point revêtues des signatures du tireur et de l'endosseur

[Acte. 1776-03-13. Paris]

Are Simple Signatures So Easy to Simulate?

Is it possible to perfectly simulate a signature, in the particular and challenging case where the signature is simple? A set of signatures of six writers, considered to be simple on the basis of highlighted criteria, was sampled. These signatures were transferred to forgers requested to produce freehand simulations. Among these simulations, those capable of reproducing the features of the reference signatures were submitted for evaluation to forensic document experts through proficiency testing. The results suggest that there is no perfect simulation. With the supplementary aim of assessing the influence of forger's skills on the results, forgers were selected from three distinct populations, which differ according to professional criteria. The results indicate some differences in graphical capabilities between individuals. However, no trend could be established regarding age, degrees, years of practice and time dedicated to the exercise. The findings show that simulation is made easier if a graphical compatibility exists between the forger's own writing and the signature to be reproduced. Moreover, a global difficulty to preserve proportions and slant as well as the shape of capital letters and initials has been noticed.

Transcriptome analysis of intraspecific competition in Arabidopsis thaliana reveals organ-specific signatures related to nutrient acquisition and general stress response pathways.

ABSTRACT: BACKGROUND: Plants are sessile and therefore have to perceive and adjust to changes in their environment. The presence of neighbours leads to a competitive situation where resources and space will be limited. Complex adaptive responses to such situation are poorly understood at the molecular level. RESULTS: Using microarrays, we analysed whole-genome expression changes in Arabidopsis thaliana plants subjected to intraspecific competition. The leaf and root transcriptome was strongly altered by competition. Differentially expressed genes were enriched in genes involved in nutrient deficiency (mainly N, P, K), perception of light quality, and responses to abiotic and biotic stresses. Interestingly, performance of the generalist insect Spodoptera littoralis on densely grown plants was significantly reduced, suggesting that plants under competition display enhanced resistance to herbivory. CONCLUSIONS: This study provides a comprehensive list of genes whose expression is affected by intraspecific competition in Arabidopsis. The outcome is a unique response that involves genes related to light, nutrient deficiency, abiotic stress, and defence responses.

Interrogating eleven fast-evolving genes for signatures of recent positive selection in worldwide human populations

Different signatures of natural selection persist over varying time scales in our genome, revealing possible episodes of adaptative evolution during human history. Here, we identify genes showing signatures of ancestral positive selection in the human lineage and investigate whether some of those genes have been evolving adaptatively in extant human populations. Specifically, we compared more than 11,000 human genes with their orthologs inchimpanzee, mouse, rat and dog and applied a branch-site likelihood method to test for positive selection on the human lineage. Among the significant cases, a robust set of 11 genes were then further explored for signatures of recent positive selection using SNP data. We genotyped 223 SNPs in 39 worldwide populations from the HGDP Diversity panel and supplemented this information with available genotypes for up to 4,814 SNPs distributed along 2 Mb centered on each gene. After exploring the allele frequency spectrum, population differentiation and the maintainance of long unbroken haplotypes, we found signals of recent adaptative phenomena in only one of the 11 candidate gene regions. However, the signal ofrecent selection in this region may come from a different, neighbouring gene (CD5) ratherthan from the candidate gene itself (VPS37C). For this set of positively-selected genes in thehuman lineage, we find no indication that these genes maintained their rapid evolutionarypace among human populations. Based on these data, it therefore appears that adaptation forhuman-specific and for population-specific traits may have involved different genes.

Comparison of molecular signatures from multiple skin diseases identifies mechanisms of immunopathogenesis.

The ability to obtain gene expression profiles from human disease specimens provides an opportunity to identify relevant gene pathways, but is limited by the absence of data sets spanning a broad range of conditions. Here, we analyzed publicly available microarray data from 16 diverse skin conditions in order to gain insight into disease pathogenesis. Unsupervised hierarchical clustering separated samples by disease as well as common cellular and molecular pathways. Disease-specific signatures were leveraged to build a multi-disease classifier, which predicted the diagnosis of publicly and prospectively collected expression profiles with 93% accuracy. In one sample, the molecular classifier differed from the initial clinical diagnosis and correctly predicted the eventual diagnosis as the clinical presentation evolved. Finally, integration of IFN-regulated gene programs with the skin database revealed a significant inverse correlation between IFN-β and IFN-γ programs across all conditions. Our study provides an integrative approach to the study of gene signatures from multiple skin conditions, elucidating mechanisms of disease pathogenesis. In addition, these studies provide a framework for developing tools for personalized medicine toward the precise prediction, prevention, and treatment of disease on an individual level.

Exploring transparent approaches to the authentication of signatures on artwork

This thesis is composed of three main parts. The first consists of a state of the art of the different notions that are significant to understand the elements surrounding art authentication in general, and of signatures in particular, and that the author deemed them necessary to fully grasp the microcosm that makes up this particular market. Individuals with a solid knowledge of the art and expertise area, and that are particularly interested in the present study are advised to advance directly to the fourth Chapter. The expertise of the signature, it's reliability, and the factors impacting the expert's conclusions are brought forward. The final aim of the state of the art is to offer a general list of recommendations based on an exhaustive review of the current literature and given in light of all of the exposed issues. These guidelines are specifically formulated for the expertise of signatures on paintings, but can also be applied to wider themes in the area of signature examination. The second part of this thesis covers the experimental stages of the research. It consists of the method developed to authenticate painted signatures on works of art. This method is articulated around several main objectives: defining measurable features on painted signatures and defining their relevance in order to establish the separation capacities between groups of authentic and simulated signatures. For the first time, numerical analyses of painted signatures have been obtained and are used to attribute their authorship to given artists. An in-depth discussion of the developed method constitutes the third and final part of this study. It evaluates the opportunities and constraints when applied by signature and handwriting experts in forensic science. A brief summary covering each chapter allows a rapid overview of the study and summarizes the aims and main themes of each chapter. These outlines presented below summarize the aims and main themes addressed in each chapter. Part I - Theory Chapter 1 exposes legal aspects surrounding the authentication of works of art by art experts. The definition of what is legally authentic, the quality and types of the experts that can express an opinion concerning the authorship of a specific painting, and standard deontological rules are addressed. The practices applied in Switzerland will be specifically dealt with. Chapter 2 presents an overview of the different scientific analyses that can be carried out on paintings (from the canvas to the top coat). Scientific examinations of works of art have become more common, as more and more museums equip themselves with laboratories, thus an understanding of their role in the art authentication process is vital. The added value that a signature expertise can have in comparison to other scientific techniques is also addressed. Chapter 3 provides a historical overview of the signature on paintings throughout the ages, in order to offer the reader an understanding of the origin of the signature on works of art and its evolution through time. An explanation is given on the transitions that the signature went through from the 15th century on and how it progressively took on its widely known modern form. Both this chapter and chapter 2 are presented to show the reader the rich sources of information that can be provided to describe a painting, and how the signature is one of these sources. Chapter 4 focuses on the different hypotheses the FHE must keep in mind when examining a painted signature, since a number of scenarios can be encountered when dealing with signatures on works of art. The different forms of signatures, as well as the variables that may have an influence on the painted signatures, are also presented. Finally, the current state of knowledge of the examination procedure of signatures in forensic science in general, and in particular for painted signatures, is exposed. The state of the art of the assessment of the authorship of signatures on paintings is established and discussed in light of the theoretical facets mentioned previously. Chapter 5 considers key elements that can have an impact on the FHE during his or her2 examinations. This includes a discussion on elements such as the skill, confidence and competence of an expert, as well as the potential bias effects he might encounter. A better understanding of elements surrounding handwriting examinations, to, in turn, better communicate results and conclusions to an audience, is also undertaken. Chapter 6 reviews the judicial acceptance of signature analysis in Courts and closes the state of the art section of this thesis. This chapter brings forward the current issues pertaining to the appreciation of this expertise by the non- forensic community, and will discuss the increasing number of claims of the unscientific nature of signature authentication. The necessity to aim for more scientific, comprehensive and transparent authentication methods will be discussed. The theoretical part of this thesis is concluded by a series of general recommendations for forensic handwriting examiners in forensic science, specifically for the expertise of signatures on paintings. These recommendations stem from the exhaustive review of the literature and the issues exposed from this review and can also be applied to the traditional examination of signatures (on paper). Part II - Experimental part Chapter 7 describes and defines the sampling, extraction and analysis phases of the research. The sampling stage of artists' signatures and their respective simulations are presented, followed by the steps that were undertaken to extract and determine sets of characteristics, specific to each artist, that describe their signatures. The method is based on a study of five artists and a group of individuals acting as forgers for the sake of this study. Finally, the analysis procedure of these characteristics to assess of the strength of evidence, and based on a Bayesian reasoning process, is presented. Chapter 8 outlines the results concerning both the artist and simulation corpuses after their optical observation, followed by the results of the analysis phase of the research. The feature selection process and the likelihood ratio evaluation are the main themes that are addressed. The discrimination power between both corpuses is illustrated through multivariate analysis. Part III - Discussion Chapter 9 discusses the materials, the methods, and the obtained results of the research. The opportunities, but also constraints and limits, of the developed method are exposed. Future works that can be carried out subsequent to the results of the study are also presented. Chapter 10, the last chapter of this thesis, proposes a strategy to incorporate the model developed in the last chapters into the traditional signature expertise procedures. Thus, the strength of this expertise is discussed in conjunction with the traditional conclusions reached by forensic handwriting examiners in forensic science. Finally, this chapter summarizes and advocates a list of formal recommendations for good practices for handwriting examiners. In conclusion, the research highlights the interdisciplinary aspect of signature examination of signatures on paintings. The current state of knowledge of the judicial quality of art experts, along with the scientific and historical analysis of paintings and signatures, are overviewed to give the reader a feel of the different factors that have an impact on this particular subject. The temperamental acceptance of forensic signature analysis in court, also presented in the state of the art, explicitly demonstrates the necessity of a better recognition of signature expertise by courts of law. This general acceptance, however, can only be achieved by producing high quality results through a well-defined examination process. This research offers an original approach to attribute a painted signature to a certain artist: for the first time, a probabilistic model used to measure the discriminative potential between authentic and simulated painted signatures is studied. The opportunities and limits that lie within this method of scientifically establishing the authorship of signatures on works of art are thus presented. In addition, the second key contribution of this work proposes a procedure to combine the developed method into that used traditionally signature experts in forensic science. Such an implementation into the holistic traditional signature examination casework is a large step providing the forensic, judicial and art communities with a solid-based reasoning framework for the examination of signatures on paintings. The framework and preliminary results associated with this research have been published (Montani, 2009a) and presented at international forensic science conferences (Montani, 2009b; Montani, 2012).

Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses.

BACKGROUND: Known antiretroviral restriction factors are encoded by genes that are under positive selection pressure, induced during HIV-1 infection, up-regulated by interferons, and/or interact with viral proteins. To identify potential novel restriction factors, we performed genome-wide scans for human genes sharing molecular and evolutionary signatures of known restriction factors and tested the anti-HIV-1 activity of the most promising candidates. RESULTS: Our analyses identified 30 human genes that share characteristics of known restriction factors. Functional analyses of 27 of these candidates showed that over-expression of a strikingly high proportion of them significantly inhibited HIV-1 without causing cytotoxic effects. Five factors (APOL1, APOL6, CD164, TNFRSF10A, TNFRSF10D) suppressed infectious HIV-1 production in transfected 293T cells by >90% and six additional candidates (FCGR3A, CD3E, OAS1, GBP5, SPN, IFI16) achieved this when the virus was lacking intact accessory vpr, vpu and nef genes. Unexpectedly, over-expression of two factors (IL1A, SP110) significantly increased infectious HIV-1 production. Mechanistic studies suggest that the newly identified potential restriction factors act at different steps of the viral replication cycle, including proviral transcription and production of viral proteins. Finally, we confirmed that mRNA expression of most of these candidate restriction factors in primary CD4+ T cells is significantly increased by type I interferons. CONCLUSIONS: A limited number of human genes share multiple characteristics of genes encoding for known restriction factors. Most of them display anti-retroviral activity in transient transfection assays and are expressed in primary CD4+ T cells.

Birth Weight, Working Memory and Epigenetic Signatures in IGF2 and Related Genes: A MZ Twin Study.

Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.

Trophic versus geographic structure in stable isotope signatures of pelagic seabirds breeding in the northeast Atlantic

Feeding ecology and geographic location are 2 major factors influencing animal stable isotope signatures, but their relative contributions are poorly understood, which limits the usefulness of stable isotope analysis in the study of animal ecology. To improve our knowledge of the main sources of isotopic variability at sea, we determined δ15N and δ13C signatures in the first primary feather of adult birds from 11 Procellariiform species (n = 609) across 16 northeast Atlantic localities, from Cape Verde (20°N) to Iceland (60°N). Post-breeding areas (where the studied feather is thought to be grown) were determined using light-level geolocation for 6 of the 11 species. Isotopic variability was geographically unstructured within the mid-northeast Atlantic (Macaronesian archipelagos), but trophically structured according to species and regardless of the breeding location, presumably as a result of trophic segregation among species. Indeed, the interspecific isotopic overlap resulting from combining δ15N and δ13C signatures of seabirds was low, which suggests that most species exploited exclusive trophic resources consistently across their geographic range. Species breeding in north temperate regions (Iceland, Scotland and Northern Ireland) showed enriched δ15N compared to the same or similar species breeding in tropical and subtropical regions, suggesting some differences in baseline levels between these regions. The present study illustrates a noticeable trophic segregation of northeast Atlantic Procellariiformes. Our results show that the isotopic approach has limited applicability for the study of animal movements in the northeast Atlantic at a regional scale, but is potentially useful for the study of long-distance migrations between large marine systems

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

Comparative performance of the stable isotope signatures of carbon, nitrogen and oxygen in assessing early vigour and grain yield in durum wheat

The present paper studied the performance of the stable isotope signatures of carbon (δ13C), nitrogen (δ15N) and oxygen (δ18O) in plants when used to assess early vigour and grain yield (GY) in durum wheat growing under mild and moderate Mediterranean stress conditions. A collection of 114 recombinant inbred lines was grown under rainfed (RF) and supplementary irrigation (IR) conditions. Broad sense heritabilities (H2) for GY and harvest index (HI) were higher under RF conditions than under IR. Broad sense heritabilities for δ13C were always above 0·60, regardless of the plant part studied, with similar values for IR and RF trials. Some of the largest genetic correlations with GY were those shown by the δ13C content of the flag leaf blade and mature grains. Under both water treatments, mature grains showed the highest negative correlations between δ13C and GY across genotypes. Flag leaf δ13C was negatively correlated with GY only under RF conditions. The δ13C in seedlings was negatively correlated, under IR conditions only, with GY but also with early vigour. The sources of variation in early vigour were studied by stepwise analysis using the stable isotope signatures measured in seedlings. The δ13C was able to explain almost 0·20 of this variation under RF, but up to 0·30 under IR. In addition, nitrogen concentration in seedlings accounted for another 0·05 of variation, increasing the amount explained to 0·35. The sources of variation in GY were also studied through stable isotope signatures and biomass of different plant parts: δ13C was always the first parameter to appear in the models for both water conditions, explaining c. 0·20 of the variation. The second parameter (δ15N or N concentration of grain, or biomass at maturity) depended on the water conditions and the plant tissue being analysed. Oxygen isotope composition (δ18O) was only able to explain a small amount of the variation in GY. In this regard, despite the known and previously described value of δ13C as a tool in breeding, δ15N is confirmed as an additional tool in the present study. Oxygen isotope composition does not seem to offer any potential, at least under the conditions of the present study.