We here review primary methods used in quantifying and mapping 5‐hydroxymethylcytosine (5hmC), including global quantification, restriction enzyme‐based detection, and methods involving DNA‐enrichment strategies and the genome‐wide sequencing of 5hmC. As discovered in the mammalian genome in 2009, 5hmC, oxidized from 5‐methylcytosine (5mC) by ten‐eleven translocation (TET) dioxygenases, is increasingly being recognized as a biomarker in biological processes from development to pathogenesis, as its various detection methods have shown. We focus in particular on an ultrasensitive single‐molecule imaging technique (...) that can detect and quantify 5hmC from trace samples and thus offer information regarding the distance‐based relationship between 5hmC and 5mC when used in combination with fluorescence resonance energy transfer. (shrink)

Outer membrane proteins (OMPs) maintain the viability of Gram‐negative bacteria by functioning as receptors, transporters, ion channels, lipases, and porins. Folding and assembly of OMPs involves synchronized action of chaperones and multi‐protein machineries which escort the highly hydrophobic polypeptides to their target outer membrane in a folding competent state. Previous studies have identified proteins and their involvement along the OMP biogenesis pathway. Yet, the mechanisms of action and the intriguing ability of all these molecular machines to work without the typical (...) cellular energy source of ATP, but solely based on thermodynamic principles, are still not well understood. Here, we highlight how different single‐molecule studies can shed additional light on the mechanisms and kinetics of OMP biogenesis. (shrink)

Macromolecular interactions play a central role in many biological processes. Protein‐protein interactions have mostly been studied by co‐immunoprecipitation, which cannot provide quantitative information on all possible molecular connections present in the complex. We will review a new approach that allows cellular proteins and biomolecular complexes to be studied in real‐time at the single‐molecule level. This technique is called single‐molecule pull‐down (SiMPull), because it integrates principles of conventional immunoprecipitation with the powerful single‐molecule fluorescence microscopy. SiMPull (...) is used to count how many of each protein is present in the physiological complexes found in cytosol and membranes. Concurrently, it serves as a single‐molecule biochemical tool to perform functional studies on the pulled‐down proteins. In this review, we will focus on the detailed methodology of SiMPull, its salient features and a wide range of biological applications in comparison with other biosensing tools. (shrink)

Eukaryotic genome DNA is wrapped around core histones and forms a nucleosome structure. Together with associated proteins and RNAs, these nucleosomes are organized three‐dimensionally in the cell as chromatin. Emerging evidence demonstrates that chromatin consists of rather irregular and variable nucleosome arrangements without the regular fiber structure and that its dynamic behavior plays a critical role in regulating various genome functions. Single‐nucleosome imaging is a promising method to investigate chromatin behavior in living cells. It reveals local chromatin motion, (...) which reflects chromatin organization not observed in chemically fixed cells. The motion data is like a gold mine. Data analyses from many aspects bring us more and more information that contributes to better understanding of genome functions. In this review article, we describe imaging of single‐nucleosomes and their tracked behavior through oblique illumination microscopy. We also discuss applications of this technique, especially in elucidating nucleolar organization in living cells. (shrink)

Molecular interactions are at the origin of life. How molecules get at different locations in the cell and how they locate their partners is a major and partially unresolved question in biology that is paramount to signaling. Spatio‐temporal correlations of fluctuating fluorescently tagged molecules reveal how they move, interact, and bind in the different cellular compartments. Methods based on fluctuations represent a remarkable technical advancement in biological imaging. Here we discuss image analysis methods based on spatial and temporal correlation (...) of fluctuations, raster image correlation spectroscopy, number and brightness, and spatial cross‐correlations that give us information about how individual molecules move in cells and interact with partners at the single molecule level. These methods can be implemented with a standard laser scanning microscope and produce a cellular level spatio‐temporal map of molecular interactions. (shrink)

Six years ago, the Singer lab published a landmark paper which described how individual mRNA particles cross the nuclear pore complex in mammalian tissue culture cells. This involved the simultaneous imaging of mRNAs, each labeled by a large number of tethered fluorescent proteins and fluorescently tagged nuclear pore components. Now two groups have applied this technique to the budding yeast Saccharomyces cerevisiae. Their results indicate that in the course of nuclear export, mRNAs likely engage complexes that are present on (...) either side of the pore and that these interactions are modulated by proteins present in the messenger ribonucleoprotein (mRNP) complex. These findings lend support to the notion that just before and/or after the completion of nuclear export, mRNPs undergo one or more maturation steps that prepare the packaged mRNAs for translation. These results represent new and exciting insights into the mechanism of mRNA nuclear export. (shrink)

While innovations in modern microscopy, spectroscopy, and nanoscopy techniques have made single molecule observation a standard in many laboratories, the actual design of meaningful fluorescence reporter systems now hinders major scientific breakthroughs. Even though the field of chemical biology is supercharging the fluorescence toolbox, surprisingly few strategies exist that make the transition from model systems to biologically relevant applications. At the same time, the number of microscopy techniques is growing dramatically. We explain our view on how the impact (...) of modern technologies is influenced not only by further hard‐ and software developments, but also by the availability and suitability of protein‐engineering tools. We identify how the largely independent research fields of chemical biology and fluorescence nanoscopy can influence each other to synergistically drive future technology that can visualize the localization, structure, and dynamics of molecular function without constraints. (shrink)

A kind of “ruthless reductionism” characterized the experimental practices of the first two decades of molecular and cellular cognition. More recently, new research tools have expanded experimental practices in this field, enabling researchers to image and manipulate individual molecular mechanisms in behaving organisms with an unprecedented temporal, sub-cellular, cellular, and even circuit-wide specificity. These tools dramatically expand the range and reach of experiments in MCC, and in doing so they may help us transcend the worn-out and counterproductive debates about “reductionism” (...) and “emergence” that divide neuroscientists and philosophers alike. We describe examples of these new tools and illustrate their practical power by presenting an exemplary recent case of MCC research using them. From these tools and results, we provide an initial sketch of a new image of the behaving organism in its full causal-interactive complexity, with its molecules, cells, and circuits combined within the single system that it is. This new image stands in opposition to the traditional “levels” image of the behaving organism, and even the initial sketch we provide of it here offers hope for avoiding the dreary metaphysical debates about “emergence” and “downward causation,” and even the reduction vs. anti-reduction dispute, all dependent upon the familiar “levels” image. (shrink)

Cryo‐electron microscopy allows the visualization of macromolecules in their native state. Combined with techniques of three‐dimensional reconstruction, cryo‐EM images of single molecules can be used to study macromolecular interactions. The ribosome, a large RNA–protein complex with multiple binding interactions, is an excellent test case illustrating the power of these new techniques. Conformational changes during the binding of tRNA and protein factors to the ribosome can now be studied without the interference of crystal packing. Now that the first X‐ray structures (...) of ribosomal subunits have become available, conformational changes observed by cryo‐EM in different functional states can be traced back to internal rearrangements of the underlying structural framework. Electron microscopy, X‐ray crystallography, and modeling should be used together in the endeavor to understand the functioning of the translational machinery. BioEssays 23:725–732, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

A new field of gene expression regulation research is emerging that has previously been overlooked. This new area is concerned with distinguishing the expression of a single gene from the averaged expression of many gene copies within the cell population. This paper reviews research focused on individual genes in inducible gene expression systems. The main experimental strategy is to measure the gene expression level of a single cell containing a single reporter gene molecule. In contrast to (...) the commonly held belief, gene induction is found to be stochastic under certain conditions. The possible mechanisms and implications are discussed. (shrink)

Inspired by the application of CycleGAN networks to the image style conversion problem Zhu et al., this paper proposes an end-to-end network, DefogNet, for solving the single-image dehazing problem, treating the image dehazing problem as a style conversion problem from a fogged image to a nonfogged image, without the need to estimate a priori information from an atmospheric scattering model. DefogNet improves on CycleGAN by adding a cross-layer connection structure in the generator to enhance the network’s multiscale feature extraction (...) capability. The loss function was redesigned to add detail perception loss and color perception loss to improve the quality of texture information recovery and produce better fog-free images. In this paper, the novel Defog-SN algorithm is presented. This algorithm adds a spectral normalization layer to the discriminator’s convolution layer to make the discriminant network conform to a 1-Lipschitz continuum and further improve the model’s stability. In this study, the experimental process is completed based on the O-HAZE, I-HAZE, and RESIDE datasets. The dehazing results show that the method outperforms traditional methods in terms of PSNR and SSIM on synthetic datasets and Avegrad and Entropy on naturalistic images. (shrink)

Magnetic resonance imaging (MRI) is an imaging technique with a rapidly expanding application range. This methodology, which relies on quantum physics and substance magnetic properties, is now being routinely used in the clinics and medical research. With the advent of measuring functional brain activity with MRI (functional MRI), this methodology has reached a larger section of the neuroscience community (e.g. psychologists, neurobiologists). In the past, the use of MRI as a biomarker or as an assay to probe tissue (...) pathophysiological condition was limited. However, with the new applications of MRI: molecular imaging, contrast‐enhanced imaging and diffusion imaging, MRI is turning into a powerful tool for in vivo characterization of tissue pathophysiology. This review focuses on the diffusion MRI. Although it only measures the averaged Brownian translational motion of water molecules, using different analysis schemes, one can extract a wide range of quantitative indices that represent tissue morphology and compartmentalization. Statistical and visualization routines help to relate these indices to biologically relevant measures such as cell density, water content and size distribution. The aim of this review is to shed light on the potential of this methodology to be used in biological research. To that end, this review is intended for the non‐MRI specialists who wish to pursue biological research with this methodology. We will overview the current applications of diffusion MRI and its relation to cellular biology of brain tissue. BioEssays 30:1235–1245, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Bacterial pathogens deliver effector proteins into host cells by deploying sophisticated secretion systems. This effector translocation during host‐pathogen interactions is a prerequisite for the manipulation of host cells and organisms and is important for pathogenesis. Analyses of dynamics and kinetics of translocation, subcellular localization, and cellular targets of effector proteins lead to understanding the mode of action and function of effector proteins in host‐pathogen interplay. This review provides an overview of biochemical and genetic tools that have been developed to study (...) protein effector translocation qualitatively or quantitatively. After introducing the challenges of analyses of effector translocation during host‐pathogen interaction, we describe various methods ranging from static visualization in fixed cells to dynamic live‐cell imaging of effector protein translocation. We show the main findings enabled by the approaches, emphasize the advantages and limitations of the methods, describe recent approaches that allow real‐time tracking of effector proteins in living cells on a single molecule level, and highlight open questions in the field to be addressed by application of new methods. (shrink)

Pointillistic based super‐resolution techniques, such as photoactivated localization microscopy (PALM), involve multiple cycles of sequential activation, imaging, and precise localization of single fluorescent molecules. A super‐resolution image, having nanoscopic structural information, is then constructed by compiling all the image sequences. Because the final image resolution is determined by the localization precision of detected single molecules and their density, accurate image reconstruction requires imaging of biological structures labeled with fluorescent molecules at high density. In such image datasets, (...) stochastic variations in photon emission and intervening dark states lead to uncertainties in identification of single molecules. This, in turn, prevents the proper utilization of the wealth of information on molecular distribution and quantity. A recent strategy for overcoming this problem is pair‐correlation analysis applied to PALM. Using rigorous statistical algorithms to estimate the number of detected proteins, this approach allows the spatial organization of molecules to be quantitatively described. (shrink)

Replication protein A (RPA), the major single‐stranded DNA‐binding protein in eukaryotic cells, is required for processing of single‐stranded DNA (ssDNA) intermediates found in replication, repair, and recombination. Recent studies have shown that RPA binding to ssDNA is highly dynamic and that more than high‐affinity binding is needed for function. Analysis of DNA binding mutants identified forms of RPA with reduced affinity for ssDNA that are fully active, and other mutants with higher affinity that are inactive. Single (...) class='Hi'>molecule studies showed that while RPA binds ssDNA with high affinity, the RPA complex can rapidly diffuse along ssDNA and be displaced by other proteins that act on ssDNA. Finally, dynamic DNA binding allows RPA to prevent error‐prone repair of double‐stranded breaks and promote error‐free repair. Together, these findings suggest a new paradigm where RPA acts as a first responder at sites with ssDNA, thereby actively coordinating DNA repair and DNA synthesis. (shrink)

Conformational changes of proteins and other biomolecules play a fundamental role in their functional mechanism. Single pair Förster resonance energy transfer offers the possibility to detect these conformational changes and dynamics, and to characterize their underlying kinetics. Using spFRET on microscopes with different modes of detection, dynamic timescales ranging from nanoseconds to seconds can be quantified. Confocal microscopy can be used as a means to analyze dynamics in the range of nanoseconds to milliseconds, while total internal reflection fluorescence microscopy (...) offers information about conformational changes on timescales of milliseconds to seconds. While the existence of dynamics can be directly inferred from the FRET efficiency time trace or the correlation of FRET efficiency and fluorescence lifetime, additional computational approaches are required to extract the kinetic rates of these dynamics, a short overview of which is given in this review. The functional mechanism of proteins is often driven by underlying conformational changes. These intramolecular changes and dynamics can be investigated using single pair Förster resonance energy transfer. The kinetic timescales of the dynamics in the range of nanoseconds to seconds is then quantified using different experimental and analytical implementations. (shrink)

Since the realisation that the antigen‐binding regions of antibodies, the variable (V) regions, can be uncoupled from the rest of the molecule to create fragments that recognise and abrogate particular protein functions in cells, the use of antibody fragments inside cells has become an important tool in bioscience. Diverse libraries of antibody fragments plus in vivo screening can be used to isolate single chain variable fragments comprising VH and VL segments or single V‐region domains. Some of (...) these are interfering antibody fragments that compete with protein‐protein interactions, providing lead molecules for drug interactions that until now have been considered difficult or undruggable. It may be possible to deliver or express antibody fragments in target cells as macrodrugs per se. In future incarnations of intracellular antibodies, however, the structural information of the interaction interface of target and antibody fragment should facilitate development of binding site mimics as small drug‐like molecules. This is a new dawn for intracellular antibody fragments both as macrodrugs and as precursors of drugs to treat human diseases and should finally lead to the removal of the epithet of the ‘undruggable’ protein‐protein interactions. (shrink)

We compare methods of aggregating repeated decisions from a single decision maker to improve medical image decision making using metacognitive processes (confidence judgments) and representational similarity from artificial neural networks for both novice and expert participants.

The human sensory experience of submolecular phenomena is only possible through complex technological mediations that include not just magnifications, but also manipulations of time and translations from one sense to another. In my creative moving image project Wildly Oscillating Molecules, I develop strategies for using an atomic force microscope (AFM) as a cinematographic instrument, specifically using its tactile mechanisms to generate video. Using the AFM over four years to generate experimental moving image installations, I examine my physical and psychological experiences (...) of this nanoscientific instrumentation. Although referred to by the philosopher of technology Don Ihde, the AFM's style of technological mediation has not been subjectively explored. Working to engage with an infinitesimal scale, the AFM has a unique style of spatial and temporal mediation that can be manipulated through the post-production and exhibition practices of the moving image. Wildly Oscillating Molecules provides insight into how the AFM influences human spatial and temporal perception of nanoscale phenomena and provides a new framework with which to analyse nanoscientific imaging practices. Understanding the nuances of technological mediation encourages science artists working with submolecular phenomena to adopt, evolve or transform properties of technological mediation when presenting their work to an audience. (shrink)

In developing a new theory of vision in Ad Vitellionem paralipomena Kepler introduced a new optical concept, pictura, which is an image projected on to a screen by a camera obscura. He distinguished this pictura from an imago, the traditional image of medieval optics that existed only in the imagination. By the 1670s a new theory of optical imagery had been developed, and Kepler's pictura and imago became real and virtual images, two aspects of a unified concept of image. The (...) new concept of image developed out of a synthesis of Kepler's determination of the geometrical location of a pictura as the limit, or focus, of refracted pencils of rays and the triangulation used by a single eye to determine the perceived location of an imago. The distinction between real and imaginary images was largely developed by Gilles Personne de Roberval and the Jesuits Francesco Eschinardi and Claude François Milliet Dechales. (shrink)

The paper is an introduction to the third issue of the Journal for the Philosophy of Language, Mind and the Arts. The authors give an account of the theories that have most enriched the study of images since the second half of the twentieth century: analytical philosophy and visual culture studies. A distinction is made between the two philosophical traditions. On the one hand, in particular within the context of analytic philosophy, images have been studied as single entities in (...) relationship with both a referent and the perceptual or interpretive abilities of an observer. On the other hand, thanks in particular to the iconographic tradition inaugurated by Aby Warburg, images have been analyzed in their multiplicity, in their mutual relationship, both synchronically and diachronically. (shrink)

Some photographs show determinate features of a scene because the photographed scene had those features. This dependency relation is, rightly, a consensus in philosophy of photography. I seek to refute many long-established theories of photography by arguing that they are incompatible with this commitment. In Section II, I classify accounts of photography as either single-stage or multi-stage. In Section III, I analyze the historical basis for single-stage accounts. In Section IV, I explain why the single-stage view led (...) scientists to postulate “latent” photographic images as a technical phenomenon in early chemical photography. In Section V, I discredit the notion of an invisible latent image in chemical photography and, in Section VI, extend this objection to the legacy of the latent image in digital photography. In Section VII, I appeal to the dependency relation to explain why the notion of a latent image makes the single-stage account untenable. Finally, I use the multi-stage account to advance debate about “new” versus “orthodox” theories of photography. (shrink)

Many employers assess their workforces with gendered and racialized imagery that can put groups of workers and applicants at a disadvantage in the labor market. Based on 78 interviews with white employers in Atlanta, the author reveals that some employers use a complex but widely shared stereo-type of Black working-class women as single mothers to typify members of this group. These employers use this single-mother image to explain why they think Black women are poor workers, why they think (...) Black women are reliable workers, and why they think Blacks are poorly prepared for the labor market. In focusing on these white employers' claims, the author concentrates not on the well-documented out-comes of labor market discrimination, such as differential rates of pay and promotion, but on how employers construct and use the images that may from the basis of it. This is especially relevant amid current attacks on affirmative action programs. (shrink)

Major problems in cancer chemotherapy are toxicity, resistance, and cancer heterogeneity. A new theranostic paradigm has been proposed by the authors. Many million small molecules (SM) are bound to the proteins extracted from a patient's cancer. SM that also bind proteins extracted from normal human tissues are subtracted from the cancer protein bound SM leaving a large array of SM targeting many sites on each of the cancer biomarkers. Targeting many more than the conventional 1 – 4 cancer biomarkers will (...) reduce development of tumor resistance. After several cycles of selection and counter selection, DNA codes appended to the SM will be PCR amplified to provide templates for restricted libraries of the SM to improve selectivity and sensitivity. The large array of selected and counter selected SM assures that many of the compounds in the array will penetrate the cell membrane and bind to intracellular targets, low tumor resistance, low background for imaging, low therapeutic toxicity, and targeting of the diverse biomarkers present in the heterogeneous mixture of cells in primary and metastatic cancer. Theranostic use of radiolabeled SM binding many sites on many, not necessarily critical, biomarkers provides high cancer cell killing. Experiments to provide proof of principle of this novel concept suggested by the authors. -/- . (shrink)

Both W9 and OP3‐4 were known to bind the receptor activator of NF‐κB ligand (RANKL), inhibiting osteoclastogenesis. Recently, both peptides were shown to stimulate osteoblast differentiation; however, the mechanism underlying the activity of these peptides remains to be clarified. A primary osteoblast culture showed that rapamycin, an mTORC1 inhibitor, which was recently demonstrated to be an important serine/threonine kinase for bone formation, inhibited the peptide‐induced alkaline phosphatase activity. Furthermore, both peptides promoted the phosphorylation of Akt and S6K1, an upstream (...) class='Hi'>molecule of mTORC1 and the effector molecule of mTORC1, respectively. In the in vivo calvarial defect model, W9 and OP3‐4 accelerated BMP‐2‐induced bone formation to a similar extent, which was confirmed by histomorphometric analyses using fluorescence images of undecalcified sections. Our data suggest that these RANKL‐binding peptides could stimulate the mTORC1 activity, which might play a role in the acceleration of BMP‐2‐induced bone regeneration by the RANKL‐binding peptides. (shrink)

A comprehensive theory of the structure and cognitive function of the human imagination, and its relationship to perceptual experience, is developed, largely through a critique of the account propounded in Colin McGinn's Mindsight. McGinn eschews the highly deflationary (and unilluminating) views of imagination common amongst analytical philosophers, but fails to develop his own account satisfactorily because (owing to a scientifically outmoded understanding of visual perception) he draws an excessively sharp, qualitative distinction between imagination and perception (following Wittgenstein, Sartre, and others), (...) and because of his fatally flawed, empirically ungrounded conception of hallucination. In fact, however, an understanding of perception informed by modern visual science will enable us to unify our accounts of perception, mental imagery, dreaming, hallucination, creativity, and other aspects of imagination within a single coherent theoretical framework. (shrink)

My topic is a certain view about mental images: namely, the ‘Multiple Use Thesis’. On this view, at least some mental image-types, individuated in terms of the sum total of their representational content, are potentially multifunctional: a given mental image-type, individuated as indicated, can serve in a variety of imaginative-event-types. As such, the presence of an image is insufficient to individuate the content of those imagination-events in which it may feature. This picture is argued for, or (more usually) just assumed (...) to be true, by Christopher Peacocke, Michael Martin, Paul Noordhof, Bernard Williams, Alan White, and Tyler Burge. It is also presupposed by more recent authors on imagination such as Amy Kind, Peter Kung and Neil Van Leeuwen. I reject various arguments for the Multiple Use Thesis, and conclude that instead we should endorse SINGLE: a single image-type, individuated in terms of the sum total of its intrinsic representational content, can serve in only one imagination event-type, whose content coincides exactly with its own, and is wholly determined by it. Plausibility aside, the interest of this thesis is also in its iconoclasm, as well as the challenge it poses for the diverse theories that rest on the truth of the Multiple Use Thesis. (shrink)

This dissertation works out a new approach to understanding what makes a representation pictorial and what makes a representation imagistic. Over the last thirty years, the most common approach to these problems has been to claim that what makes a representation pictorial is that normal perceivers can perceive it in certain ways. By contrast, my approach singles out structural features of representational systems as that which distinguishes pictures from other kinds of representations. Pictorial systems are those that are transparent, relatively (...) syntactically sensitive, relatively replete, and semantically rich. All pictures are images, but the converse relation does not hold because images need not be transparent, though they satisfy the weaker condition of being mimetic. This approach is similar to, but enjoys advantages over, Nelson Goodman's work on the topic. ;The account of what makes a representation pictorial or imagistic is then brought to bear on the imagery debate, which concerns whether the brain implements imagistic systems of representation, specifically in the early stages of perception. A review of what we know about the workings of the visual and auditory systems reveals that no representations in the brain are pictorial, though some are imagistic in quite limited respects. Though they fail to be imagistic in many interesting respects, the early stages of the visual and auditory systems are highly isomorphic to what they represent. ;The role of isomorphism in perceptual states has been much discussed in both philosophy and cognitive neuroscience. The last two chapters of the dissertation argue that perceptual representations of traditionally secondary qualities like colors and sounds are isomorphic to those properties to a lesser degree than representations of traditionally primary qualities like shapes. This distinction in how such properties are represented can affect out intuitions concerning the nature of those properties and the nature of perceptual experience. Furthermore, it is argued that isomorphism is an important feature of perceptual representations because of the role it plays in making information cognitively available. This role for isomorphism is maintained even if one is an information theorist, and therefore thinks that lawful causal generalizations fix the content of representations. (shrink)

In this chapter, I argue that genuinely abstract images do not depict but have aboutness, nevertheless. All images have aboutness in virtue of the visual configurations on their surfaces: it is through those configurations that they can convey something – they can mean something, represent something, express something, and so on. On the one hand, in depictive images, the visual configurations on the images’ surfaces depict visible objects while abstracting completely from some of their visual proper- ties. In Giovanni Bellini’s (...) Portrait of Doge Leonardo Loredan (1501), for instance, the visual configurations on the pictorial surface depict Doge Loredan’s head and torso, as seen frontally. The image, however, com- pletely abstracts from, e.g., Doge Loredan’s legs, nape, and back. On the other hand, as I shall argue, when the visual configurations on a two- dimensional surface do not depict anything at all but have aboutness in ways other than the depictive, that two-dimensional surface is a genu- inely abstract image. As I shall show, all genuinely abstract images entirely abstain from depicting but can nevertheless abstract in different measures from the visual properties of objects. The first step for an account of genuinely abstract images is to distin- guish accurately between depictive images and genuinely abstract ones. For this, one needs an account of depiction – this is provided in the first section of this chapter. In the second section, different kinds of depictive images are singled out: this facilitates focusing on images that qualify as genuinely abstract. In the third section, four ways in which genuinely abstract images have aboutness are discussed: conventionality, indexicality, exemplifica- tion, and expressivity. The fourth section concludes with some general observations on the peculiarities of genuinely abstract images. (shrink)

A photographic image is said to provide evidence of a photographed scene because it is a causal imprint of reflected light, an indexical trace of real objects and events. Though widely established in the history, theory, and philosophy of photography, this traditional imprinting model must be rejected because it relies on a “single-stage” misconception of the photographic process: the idea that a photographic image comes into existence at the time of exposure. In its place, a “multistage” account properly articulates (...) different production stages, such as registering and rendering, that are relevant to understanding the relation between a photographic image and the photographed scene. By denying that any photographic image is a causal imprint, the multistage approach proposes a more demanding evaluation of photographic evidence. This has implications for documentary film and photojournalism, along with specialized applications such as forensics, surveillance, and face-recognition technology. (shrink)

Ghost Image is made up of sixty-three short essays—meditations, memories, fantasies, and stories bordering on prose poems—and not a single image. Hervé Guibert’s brief, literary rumination on photography was written in response to Roland Barthes’s Camera Lucida, but its deeply personal contents go far beyond that canonical text. Some essays talk of Guibert’s parents and friends, some describe old family photographs and films, and spinning through them all are reflections on remembrance, narcissism, seduction, deception, death, and the phantom images (...) that have been missed. Both a memoir and an exploration of the artistic process, Ghost Image not only reveals Guibert’s particular experience as a gay artist captivated by the transience and physicality of his media and his life, but also his thoughts on the more technical aspects of his vocation. In one essay, Guibert searches through a cardboard box of family portraits for clues—answers, or even questions—about the lives of his parents and more distant relatives. Rifling through vacation snapshots and the autographed images of long-forgotten film stars, Guibert muses, “I don’t even recognize the faces, except occasionally that of an aunt or great-aunt, or the thin, fair face of my mother as a young girl.” In other essays, he explains how he composes his photographs, and how—in writing—he seeks to escape and correct the inherent limits of his technique, to preserve those images lost to his technical failings as a photographer. With strains of Jean Genet and recurring themes that speak to the work of contemporary artists across a range of media, Guibert’s Ghost Image is a beautifully written, melancholic ode to existence and art forms both fleeting and powerful—a unique memoir at the nexus of family, memory, desire, and photography. (shrink)

While much has been written about verbal narratives, we still lack a clear account of what makes images narrative. I argue that there are narrative characteristics of images and show this with examples of single images. The argument proceeds in three steps. First, I propose that from a semantic perspective, the following two characteristics are necessary for an image to be narrative: a representation of an event and a representation of time. Second, I argue that there are paradigmatic characteristics, (...) such as at least two events, bridging connections, and unifying subjects between these events, characters with intentions, and the representation of goal-directed actions. Third, I show that it is possible to differentiate between narrative and non-narrative images while also accounting for the idea that narrativity is a matter of degree. While I do not provide a full definition of narrative images, my account constitutes a necessary first step in this direction. (shrink)

We can say that Picasso’s images speak to us, and, as writing, speak to us from that space in which any text – far from being reduced to a single sense – “disseminates” its “truths”. Using the figure and the story of the Minotaur, Picasso devoted himself to one of the great themes of his pictorial work. The word “labyrinth” connotes, to the European mind, Greece, Knossos, Dedalus, Ariadne and the Minotaur. However, the Greek formula already represents a mythic (...) and poetic outcome thoroughly developed from an imagery forged in the remotest eras of our evolution. The relationship between the image, the spiral, and the word, labyrinth is also linked to the perception of a drilled earth, excavated, with numberless tortuous tunnels which, in our imagination, provoke concern because they lead to the world of the inferi, the unknown depths of the realms of the dead. Juan Larrea, a little-known essayist in the sphere of philosophical studies, although, from the outset of international renown for Picasso’s work, he gives what is perhaps the best interpretation of Guernica and consequently also sheds much light on the engravings immediately preceding the execution of this painting, the Minotauromachy among them. The artist is not a prophet. He is not foreseeing what the future holds for humanity, but he does possess a heightened sensitivity that drives him to minutely scrutinise the conditions of the time that he has had to live, and he has a transforming eye for the symbols that constitute the deepest threads in the fabric of his culture. (shrink)

The recent development of single molecule detection techniques has opened new horizons for the study of individual macromolecules under physiological conditions. Conformational subpopulations, internal dynamics and activity of single biomolecules, parameters that have so far been hidden in large ensemble averages, are now being unveiled. Herein, we review a particular attractive solution‐based single molecule technique, fluorescence correlation spectroscopy (FCS). This time‐averaging fluctuation analysis which is usually performed in Confocal setups combines maximum sensitivity with high statistical (...) confidence. FCS has proven to be a very versatile and powerful tool for detection and temporal investigation of biomolecules at ultralow concentrations on surfaces, in solution, and in living cells. The introduction of dual‐color cross‐correlation and two‐photon excitation in FCS experiments is currently increasing the number of promising applications of FCS to biological research. BioEssays 24:758–764, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The Adventure of the Image Through the Conflict of Interpretations. Starting from the self-image, through the image adventure landscape seen as an ensemble of conflict of interpretation, not only from a single glance or direction, whether it is evasive or complex, we follow our decipherment and transformation, be it process or state. Through multiple hypostases, whether isolated or open, I will focus on certain details that will be addressed as a dimension by means of text or material reproduction, or (...) through the passage of the same image we face each time through the filter of our own existence. We stop the other or ourselves against the other, thus removing the observer or viewer, thus providing not only distinct perspectives on the same subject or the same situation or even the same consequences, but also giving him the opportunity to choose how to relate to the internal and external environment, thus convincing that, to a lesser extent, or greater, he is the one who drives everything. This approach is based not only on the adventure of self-image in the archive of own experiences but also from the outside, from the archive of common experiences perceived by other people. (shrink)

In a recent article, Dawn Wilson (2021) has argued against single-stage accounts of photography by arguing against the latent photographic images upon which those accounts depend. Concomitantly, she argues that the only viable account of photography is multi-stage. Unlike single-stage accounts, multi-stage accounts do not postulate the existence of photographic images of any kind prior to development. Rather, according to multi-stage accounts, photographs are produced from “photographic registers.” In this Discussion Piece, I defend single-stage accounts by arguing (...) that Wilson’s rejection of latent photographic images is premised on an implausible view of what a latent photographic image is. Given a reasonable interpretation, the latent images described in single-stage accounts just are the photographic registers described in multi-stage accounts. (shrink)

This article proposes a semio-rhetorical epistemology for visual documents, one capable of accounting for both their internal configuration, which we shall call the compositional dimension, and their persuasive force within public space, or their rhetorical dimension. The field of reference will be that of identity-related images on social networks, because compared to other kinds of images, such as artistic or professional ones, they adopt new compositional solutions and new dynamics of circulation. To test this theoretical framework, we will conduct an (...) analysis which has never been carried out in semiotics and which, as far as we know, remains very rare even in the overall field of visual studies, that is, the analysis of the profile of an Instagram influencer’s visual production, that of Canadian artist Rupi Kaur. Taking into account the flow of images shared over time, we will focus primarily on the compositional dimension that articulates the specificity of the language of images. The most appropriate model for investigating social network photos seems to be that of the portrait, thanks to which we will identify a first series of regularities and deviations. Secondly, we will turn towards the rhetorical dimension – the persuasive strategies found within, through, and towards images – focusing on the analysis of a single photo: on the one hand, it is a shot which presents greater compositional richness than others; on the other hand, it has greatly impacted the notoriety of the influencer, due to the censorship incurred on Instagram, its abundant coverage by traditional media, and the heated debate it triggered on social media. We will thus propose a reinterpretation of Paul Ricœur’s theory of identity in order to balance the rhetorical and the compositional dimensions through a unitary theoretical hypothesis. Visual identity on social networks is always the result of a negotiation between two opposite tendencies: on the one hand, the experiential pressure expressed through images related to the body and everyday practices; on the other, the algorithmic pressure due to the delegation of the management of identity to software. The case of Rupi Kaur is a rare example of a critical mediation between these two pressures and helps us build a methodology for the examination of images belonging to other social domains. (shrink)

The genetic stability of living cells is continuously threatened by the presence of endogenous reactive oxygen species and other genotoxic molecules. Of particular threat are the thousands of DNA single-strand breaks that arise in each cell, each day, both directly from disintegration of damaged sugars and indirectly from the excision repair of damaged bases. If un-repaired, single-strand breaks can be converted into double-strand breaks during DNA replication, potentially resulting in chromosomal rearrangement and genetic deletion. Consequently, cells have adopted (...) multiple pathways to ensure the rapid and efficient removal of single-strand breaks. A general feature of these pathways appears to be the extensive employment of protein–protein interactions to stimulate both the individual component steps and the overall repair reaction. Our current understanding of DNA single-strand break repair is discussed, and testable models for the architectural coordination of this important process are presented. BioEssays 23:447–455, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Rod photoreceptors are among the most sensitive light detectors in nature. They achieve their remarkable sensitivity across a wide variety of species through a number of essential adaptations: a specialized cellular geometry, a G‐protein cascade with an unusually stable receptor molecule, a low‐noise transduction mechanism, a nearly perfect effector enzyme, and highly evolved mechanisms of feedback control and receptor deactivation. Practically any change in protein expression, enzyme activity, or feedback control can be shown to impair photon detection, either by (...) decreasing sensitivity or signal‐to‐noise ratio, or by reducing temporal resolution. Comparison of mammals to amphibians suggests that rod outer‐segment morphology and the molecules and mechanism of transduction may have evolved together to optimize light sensitivity in darkness, which culminates in the extraordinary ability of these cells to respond to single photons at the ultimate limit of visual perception. (shrink)

When we look at a tree, two images of it are formed, one on each of our retinas. Why, then, asks the child or the philosopher, do we not see two trees?1 Thomas Reid offers an answer to this question in the section of his Inquiry into the Human Mind entitled ‘Of seeing objects single with two eyes’. The principles he invokes in his answer serve at the same time to explain why we do occasionally see objects double. In (...) Part I of this essay, I examine the principles Reid uses to explain single and double vision. This part is mostly an exercise in the history of cognitive science, but it raises questions of interest to philosophers along the way. In Part II, I turn to a hard-core philosophical problem raised by double vision, namely, whether double vision constitutes an objection to the direct realist theory of perception, which was one of Reid's main philosophical purposes to promote. (shrink)

In the past decades, considerable attention has been paid to the chaos-based image encryption schemes owing to their characteristics such as extreme sensitivity to initial conditions and parameters, pseudo-randomness, and unpredictability. However, some schemes have been proven to be insecure due to using a single chaotic system. To increase the security, this work proposes a novel image encryption scheme based on the piecewise linear chaotic map and the standard map. To the best of our knowledge, it is the first (...) chaos-based image encryption scheme combining the PWLCM with the standard map, which adopts permutation-diffusion structure. Unlike the traditional scrambling way, a hierarchical diffusion strategy, which not only changes the pixel position but also modifies the value, is employed in the permutation phase. The operation model of row-by-row and column-by-column is further used to enhance the efficiency in the diffusion process. Consequently, a good trade-off efficiency and security can be achieved. Furthermore, the numerical simulations and performance analyses illustrate that the proposed encryption scheme can be used in practical application scenarios requiring lightweight security. (shrink)

In a digital communication environment, information security is mandatory. Three essential parameters used in the design process of a steganography algorithm are Payload, security, and fidelity. However, several methods are implemented in information hiding, such as Least Significant Bit (LBS), Discrete Wavelet Transform, Masking, and Discrete Cosine Transform. The paper aims to investigate novel steganography techniques based on agent technology. It proposes a Framework of Steganography based on agent for secret communication using LSB. The most common image steganography databases are (...) explored for training and testing. The methodology in this work is based on the statistical properties of the developed agent software using Matlab. The experiment design is based on six statistical feature measures, including Histogram, Mean, Standard deviation, Entropy, Variance and Energy. For steganography, an Ensemble classifier is used to test two scenarios: embedding a single language message and inserting bilingual messages. ROC Curve represents the evaluation metrics. The result shows that the designed agent-based system with 50% training/testing sample set and 0.2 Payload can pick out the best cover image for the provided hidden message size to avoid visual artifact. (shrink)

Since the nineteenth and twentieth century, information has been pivotal both in the cultural tradition and then in the economic tradition. While the Fordism economic model and its specialisation requirements originated a simplistic zoning and single-use development approach to the design of a city. It, however, determined a fragmented growth of cities. Inevitably, the zoning as an urban strategy affected the architectural scale. Nevertheless, the idea of information, commercial goods and thereby people freely able to flow through the city (...) allowed architects and urban designer to conceive new types of urban infrastructures. For example, trains, which were designed on the model of urban “arteries and veins.” Over time, the persistence of urban and architectural segmentation has strengthened social and economic inequalities among urban society. In addition, information has played a more vital role in this strengthening process. The technological achievements of the twenty-first century such as information technologies have significantly affected cities. The new informational patterns have provided new ways of designing, and in turn how societies experience cities. These “quantified cities” consist of digital data that dynamically interacts with “quantified human beings.” Consequently, a renewed urban semiotics is established, which is built around an alternate sociological comprehension. Is this new urban semiotics able to heal an ill and divided urban body? The paper will investigate a new concept of “quantified city” based on the notion of “Hyper-Reality,” and its inhabitants who are entering in a “post-human” condition while living in a dynamic urban environment. In particular, the critical analysis will be used as a “tool” for redefining the perception of the city through inhabitants’ relational patterns which are technologically mediated. The more traditional notion of urbanisation is questioned with a focus on how the an urban society is embedded within the digital condition and the notion of a city. (shrink)

Precise and timely diagnosis of Parkinson’s disease is important to control its progression among subjects. Currently, a neuroimaging technique called dopaminergic imaging that uses single photon emission computed tomography (SPECT) with 123I-Ioflupane is popular among clinicians for detecting Parkinson’s disease in early stages. Unlike other studies, which consider only low-level features like gray matter, white matter, or cerebrospinal fluid, this study explores the non-linear relation between different biomarkers (SPECT + biological) using deep learning and multivariate logistic regression. Striatal (...) binding ratios are obtained using 123I-Ioflupane SPECT scans from four brain regions which are further integrated with five biological biomarkers to increase the diagnostic accuracy. Experimental results indicate that this investigated approach can differentiate subjects with 100% accuracy. The obtained results outperform the ones reported in the literature. Furthermore, logistic regression model has been developed for estimating the Parkinson’s disease onset probability. Such models may aid clinicians in diagnosing this disease. (shrink)

We have been using feather development as a model for understanding the molecular basis of pattern formation and to explore the roles of homeoproteins, retinoids and adhesion molecules in this process. Two kinds of homeobox (Hox) protein gradients in the skin have been identified: a ‘microgradient’ within a single feather bud and a ‘macrogradient’ across the feather tract. The asynchronous alignment of different Hox macrogradients establishes a unique repertoire of Hox expression patterns in skin appendages within the integument, designated (...) here as the ‘Hox codes of skin appendages’. It is hypothesized that these Hox codes contribute to the phenotypic determination of skin appendages. High doses of retinoic acid cause a morphological transformation between feather and scale, while low doses of retinoic acid cause an alteration of the axial orientation of skin appendages. We have tested the ability of molecules directly involved in the feather formation process to mediate the action of the Hox codes, and surmise that adhesion molecules are potential candidates. Using specific Fabs to suppress the activity of adhesion molecules, we have found that L‐CAM is involved in the formation of the hexagonal pattern, N‐CAM is involved in mediating dermal condensations, tenascin is involved in feather bud growth and elongation, and integrin β‐1 is essential for epithelial‐mesenchymal interactions. More work is in progress to fully understand the molecular pathways regulating the feather formation process. (shrink)

Birth asphyxia is the most common single cause of death in term newborn infants. The majority of deaths in developed countries follow decisions to withdraw intensive care. Recent technological advances, particularly the use of magnetic resonance imaging (MRI) of the brain, may affect the process of prognostication and decision-making. There is little existing evidence about how prognosis is determined in newborn infants and how this relates to treatment withdrawal decisions.An exploratory qualitative study was performed using in-depth semi-structured interviews (...) with a sample of ten neonatologists from tertiary intensive care units in the UK. Participants were purposively selected to ensure a range of experience and type of unit. They were asked about the process of prognostication for infants with birth asphyxia and decisions about treatment withdrawal. Interviews were transcribed and thematically analysed.MRI played a significant role in decision-making about life-sustaining treatment for a number of clinicians. Clinicians did not identify particular ethical concerns related to MRI, though wider discussion revealed issues relating to uncertainty around predictions, the timing of prognostication and decision-making, and difficulty in predicting quality of life. (shrink)

This study tested whether compassionate goals to support others and self-image goals to maintain and defend desired self-images: 1) are equivalent constructs across three cultures ; 2) overlap with interdependent self-construal; and 3) predict relationships and growth measures similarly in each country. We re-analyzed data from American and Japanese students, reported in Niiya et al., along with new data from Poland. Single and multiple group confirmatory analyses showed that the two-factor structure holds across the three cultures. Interdependence correlated with (...) compassionate and self-image goals only in Japan. In all three samples, compassionate goals correlated with non-zero-sum belief, feeling close, growth-seeking, self-compassion, and learning from failures, whereas self-image goals correlated with defensive responses to conflicts and validation-seeking. Our results suggest that compassionate and self-image goals may serve similar functions in relationships and growth across cultures. (shrink)

Providing a wide-ranging account of the narrative properties of photographs, Greg Battye focuses on the storytelling power of a single image, rather than the sequence. Drawing on ideas from painting, drawing, film, video, and multimedia, he applies contemporary research and theories drawn from cognitive science and psychology to the analysis of photographs. Using genuine forensic photographs of crime scenes and accidents, the book mines human drama and historical and sociological authenticity to argue for the centrality of the perception and (...) representation of time in photographic narrativity. (shrink)

Barbara Stafford is at the forefront of a growing movement that calls for the humanities to confront the brain’s material realities. In Echo Objects she argues that humanists should seize upon the exciting neuroscientific discoveries that are illuminating the underpinnings of cultural objects. In turn, she contends, brain scientists could enrich their investigations of mental activity by incorporating phenomenological considerations—particularly the intricate ways that images focus intentional behavior and allow us to feel thought. This, then, is a book for both (...) sides of the aisle, a stunningly broad exploration of how complex images—or patterns that compress space and time—make visible the invisible ordering of human consciousness. Stafford demonstrates, for example, how the compound formats of emblems, symbols, collage, and electronic media reveal the brain’s grappling to construct mental objects that are redoubled by prior associations. On the other hand, she compellingly shows that findings in evolutionary biology and the neurosciences are providing profound opportunities for understanding aesthetic conundrums as old and deep-seated as the human urge to imitate, the mapping of inner space, and the role of narrative and nonnarrative representation. As precise in her discussions of firing neurons as she is about the coordinating dynamics of image making, Stafford locates these major transdisciplinary issues at the intersection of art, science, philosophy, and technology. Ultimately, she makes an impassioned plea for a common purpose—for the acknowledgement that, at the most basic level, these separate projects belong to a single investigation. (shrink)

A recent paper by Watabe et al.(1) describes the identification, in the promoter region of the organizer‐specific gene goosecoid, of two distinct growth factor responsive elements that are required for the regulation of this gene both in vitro and in vivo. This is an important finding since it provides molecular evidence in support of the recently proposed model in which the production of dorsal type mesoderm is thought to require a synergistic interaction between a general mesoderm inducing factor and (...) a dorsalizing competence modifier(2,6–8). Furthermore, the authors provide an elegant example of how a response element can become a useful tool to map the presence of a biologically available ligand within the embryo. (shrink)