Play, Free Association, and Enactment.

In this article I define childhood symbolic play, free association, and enactments as distinct entities despite the important strands of connective tissue that bind them psychologically. To Freud's definition of play being the same as fantasy, except for play's need to use props and playthings to actualize itself, I add action as an obvious but yet nevertheless neglected component of childhood symbolic play. I suggest that the potential for free association begins with the achievement of formal Piagetian cognitive processes in early adolescence, an achievement that needs no props or actions to set it in motion since words and ideas generate further spontaneities in a creative flow of associations. In adult psychoanalytic process, I define enactment, not only in the modern sense of a shared unconscious communication that illustrates the complementarity of countertransference/transference mutuality, but as if enactment could be isolated from its enmeshment in the countertransference/transference milieu of analytic process and viewed momentarily as a transference entity exclusively. I take this point of view to emphasize longitudinally, an individual's action in a developmental sequence, an imaginary developmental line from the six stages of sensorimotor actions that lead to symbolism, to thought as trial action, leading on then to symbolic play and to free association in adolescence, free associative communication being the essential core of analytic process despite the ubiquity of enactments that accompany it. I illustrate this imagined developmental line, which leads from the earliest sensorimotor acts to the decisive non-neurotic acts that characterize individuated post-analytic maturity, with psychoanalytic process from childhood, adolescence, and adulthood.

The Evolution of Dreams: A Fifty Year Follow-Up.

A child that was analyzed from four years of age to nine returned for brief visits at age twelve, nineteen, thirty; and at fifty for a more sustained analytic engagement. He reported new dreams on each return visit. Given this contact with him for almost fifty years it has been possible to reflect on the progression of his dreams over five decades. While it is clear that dreams do reflect developmental challenges there is also a remarkable continuity of genetic themes that can be identified. While dreams do reflect different phases of development, to be sure, the persistence of initial genetic conflicts are not only reflected in symptoms and character structure but in the dream work's artistry as well, as latent content is transformed so creatively into its manifest disguises. It is this striking continuity of original genetic themes, first exposed in the child analysis, that runs like the unconscious musical drone of a ground bass throughout the first fifty years of the symphonic life of one individual, that I wish to focus on.

A Cartoon in a Dream.

A cartoon in a dream is an unusual example of an inclusion body, so to speak, planted in manifest content by the dream-work to attract special attention to what is manifest, when what is latent is in danger of exposing itself too radically. In previous publications the author has described similar, unusual, conspicuous insertions in dreams (a joke in a dream; a pun in a dream; a parapraxis in a dream; a trick in a dream; the uncanny in dreams; dreams within dreams). In all of these instances it was possible, using the free associative method of dream analysis, to lay bare the dynamic architecture of each dream and expose what the manifest razzle-dazzle of the intruding element sought to achieve. It was often the case that such elements were a last minute heroic attempt on the part of the dream-work to save an explosive dream from falling apart as highly combustible, sexual, or aggressive elements could not be reined in sufficiently to escape the dream censor's vetoing disapproval. In the current example a rather vivid cartoon image took center stage, hoping to keep the focus entirely on manifest content and leave the latent content unexamined even when the awakener begins to analyze the dream.

Silica-Coated Nanoparticles with a Core of Zinc, l-Arginine, and a Peptide Designed for Oral Delivery.

Nanoparticle constructs for oral peptide delivery at a minimum must protect and present the peptide at the small intestinal epithelium in order to achieve oral bioavailability. In a reproducible, scalable, surfactant-free process, a core was formed with insulin in ratios with two established excipients and stabilizers, zinc chloride and l-arginine. Cross-linking was achieved with silica, which formed an outer shell. The process was reproducible across several batches, and physicochemical characterization of a single batch was confirmed in two independent laboratories. The silica-coated nanoparticles (SiNPs) entrapped insulin with high entrapment efficiency, preserved its structure, and released it at a pH value present in the small intestine. The SiNP delivered insulin to the circulation and reduced plasma glucose in a rat jejunal instillation model. The delivery mechanism required residual l-arginine in the particle to act as a permeation enhancer for SiNP-released insulin in the jejunum. The synthetic process was varied in terms of ratios of zinc chloride and l-arginine in the core to entrap the glucagon-like peptide 1 analogue, exenatide, and bovine serum albumin. SiNP-delivered exenatide was also bioactive in mice to some extent following oral gavage. The process is the basis for a platform for oral peptide and protein delivery.

Characterization of Nanoparticle Batch-To-Batch Variability.

A central challenge for the safe design of nanomaterials (NMs) is the inherent variability of NM properties, both as produced and as they interact with and evolve in, their surroundings. This has led to uncertainty in the literature regarding whether the biological and toxicological effects reported for NMs are related to specific NM properties themselves, or rather to the presence of impurities or physical effects such as agglomeration of particles. Thus, there is a strong need for systematic evaluation of the synthesis and processing parameters that lead to potential variability of different NM batches and the reproducible production of commonly utilized NMs. The work described here represents over three years of effort across 14 European laboratories to assess the reproducibility of nanoparticle properties produced by the same and modified synthesis routes for four of the OECD priority NMs (silica dioxide, zinc oxide, cerium dioxide and titanium dioxide) as well as amine-modified polystyrene NMs, which are frequently employed as positive controls for nanotoxicity studies. For 46 different batches of the selected NMs, all physicochemical descriptors as prioritized by the OECD have been fully characterized. The study represents the most complete assessment of NMs batch-to-batch variability performed to date and provides numerous important insights into the potential sources of variability of NMs and how these might be reduced.

AFFECT, SYMPTOM, FANTASY, DREAM: CLINICAL AND THEORETICAL CONSIDERATIONS.

A symptom being studied in the process of analysis can be seen as not unlike the unconscious affect it sprang from. The author presents a case in which a symptom, premature ejaculation, was analogous to the unconscious affect of guilt, which itself seemed to be a premature defensive transformation of a deeper current of anger. Guilt was interpreted as if it were a psychic premature ejaculation, a defensive derailment of anger. Fantasy and dream seemed to be engaged in similar transformations, with a fantasy of "premature incarceration" not unlike the symptom itself in its analogous functioning. Analysis of affect, symptom, fantasy, and dream in complex, integrative analytic process led not only to resolution of the symptom itself, but also to a deeper understanding of the mind's complex functioning in general.

Nanoparticle passage through porcine jejunal mucus: Microfluidics and rheology.

A micro-slide chamber was used to screen and rank sixteen functionalized fluorescent silica nanoparticles (SiNP) of different sizes (10, 50, 100 and 200 nm) and surface coatings (aminated, carboxylated, methyl-PEG1000ylated, and methyl-PEG2000ylated) according to their capacity to permeate porcine jejunal mucus. Variables investigated were influence of particle size, surface charge and methyl-PEGylation. The anionic SiNP showed higher transport through mucus whereas the cationic SiNP exhibited higher binding with lower transport. A size-dependence in transport was identified - 10 and 50 nm anionic (uncoated or methyl-PEGylated) SiNP showed higher transport compared to the larger 100 and 200 nm SiNP. The cationic SiNP of all sizes interacted with the mucus, making it more viscous and less capable of swelling. In contrast, the anionic SiNP (uncoated or methyl-PEGylated) caused minimal changes in the viscoelasticity of mucus. The data provide insights into mucus-NP interactions and suggest a rationale for designing oral nanomedicines with improved mucopermeability.

SCREEN MEMORIES: A NEGLECTED FREUDIAN DISCOVERY?

In 1899, Freud introduced the concept of screen memories. His insights were revolutionary: screen memories do not emerge into consciousness at the time of recall, he argued; they are formed at that time and, moreover, historical accuracy is not their prime concern. In this article, the author reviews two of Freud's screen memories, as well as two screen memories from a completed analysis of one of his own patients. He argues that, if screen memories are formed, a concept such as screen work must be invoked as the agent of their formation. While screen memories may theoretically be formed at any stage of life, adolescence may be a prime time for their formation.

Tuning of nanoparticle biological functionality through controlled surface chemistry and characterisation at the bioconjugated nanoparticle surface.

We have used a silica - PEG based bionanoconjugate synthetic scheme to study the subtle connection between cell receptor specific recognition and architecture of surface functionalization chemistry. Extensive physicochemical characterization of the grafted architecture is capable of capturing significant levels of detail of both the linker and grafted organization, allowing for improved reproducibility and ultimately insight into biological functionality. Our data suggest that scaffold details, propagating PEG layer architecture effects, determine not only the rate of uptake of conjugated nanoparticles into cells but also, more significantly, the specificity of pathways via which uptake occurs.

Controlling aqueous silica nanoparticle synthesis in the 10-100 nm range.

We describe the control of size and homogeneity in silica nanoparticle dispersions, prepared by a two-phase arginine catalysed aqueous method, through varying the upper organic solvent phase. The final particle dispersion characteristics can be controlled by varying features including solvent type and interfacial area, related to the rate of monomer transfer at the TEOS/water interface.

Synthetic multivalency for biological applications.

Current directions and emerging possibilities under investigation for the integration of synthetic and semi-synthetic multivalent architectures with biology are discussed. Attention is focussed around multivalent interactions, their fundamental role in biology, and current and potential approaches in emulating them in terms of structure and functionality using synthetic architectures.

Biomimetic Approach for Ion Channels Based on Surfactant Encapsulated Spherical Porous Metal-Oxide Capsules.

Distinguished hybrid clusters with hydrophilic and hydrophobic interiors embedded within cationic surfactant shells are spontaneously inserted into lipid bilayers, showing well-defined ionic conductance behaviors. The transport via the narrow pore gates acting as selectivity filters is controlled by the dehydration energy of the cations.

INSIGHT AGONISTES: A READING OF SOPHOCLES'S OEDIPUS THE KING.

In this reading of Sophocles's Oedipus the King, the author suggests that insight can be thought of as the main protagonist of the tragedy. He personifies this depiction of insight, calling it Insight Agonistes, as if it were the sole conflicted character on the stage, albeit masquerading at times as several other characters, including gods, sphinxes, and oracles. This psychoanalytic reading of the text lends itself to an analogy between psychoanalytic process and Sophocles's tragic hero. The author views insight as always transgressing against, always at war with a conservative, societal, or intrapsychic chorus of structured elements. A clinical vignette is presented to illustrate this view of insight.

The "sweet" side of the protein corona: effects of glycosylation on nanoparticle-cell interactions.

The significance of a protein corona on nanoparticles in modulating particle properties and their biological interactions has been widely acknowledged. The protein corona is derived from proteins in biological fluids, many of which are glycosylated. To date, the glycans on the proteins have been largely overlooked in studies of nanoparticle-cell interactions. In this study, we demonstrate that glycosylation of the protein corona plays an important role in maintaining the colloidal stability of nanoparticles and influences nanoparticle-cell interactions. The removal of glycans from the protein corona enhances cell membrane adhesion and cell uptake of nanoparticles in comparison with the fully glycosylated form, resulting in the generation of a pro-inflammatory milieu by macrophages. This study highlights that the post-translational modification of proteins can significantly impact nanoparticle-cell interactions by modulating the protein corona properties.

Surfactant titration of nanoparticle-protein corona.

Nanoparticles (NP), when exposed to biological fluids, are coated by specific proteins that form the so-called protein corona. While some adsorbing proteins exchange with the surroundings on a short time scale, described as a "dynamic" corona, others with higher affinity and long-lived interaction with the NP surface form a "hard" corona (HC), which is believed to mediate NP interaction with cellular machineries. In-depth NP protein corona characterization is therefore a necessary step in understanding the relationship between surface layer structure and biological outcomes. In the present work, we evaluate the protein composition and stability over time and we systematically challenge the formed complexes with surfactants. Each challenge is characterized through different physicochemical measurements (dynamic light scattering, ζ-potential, and differential centrifugal sedimentation) alongside proteomic evaluation in titration type experiments (surfactant titration). 100 nm silicon oxide (Si) and 100 nm carboxylated polystyrene (PS-COOH) NPs cloaked by human plasma HC were titrated with 3-[(3-Cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS, zwitterionic), Triton X-100 (nonionic), sodium dodecyl sulfate (SDS, anionic), and dodecyltrimethylammonium bromide (DTAB, cationic) surfactants. Composition and density of HC together with size and ζ-potential of NP-HC complexes were tracked at each step after surfactant titration. Results on Si NP-HC complexes showed that SDS removes most of the HC, while DTAB induces NP agglomeration. Analogous results were obtained for PS NP-HC complexes. Interestingly, CHAPS and Triton X-100, thanks to similar surface binding preferences, enable selective extraction of apolipoprotein AI (ApoAI) from Si NP hard coronas, leaving unaltered the dispersion physicochemical properties. These findings indicate that surfactant titration can enable the study of NP-HC stability through surfactant variation and also selective separation of certain proteins from the HC. This approach thus has an immediate analytical value as well as potential applications in HC engineering.

Multivalent recognition of concanavalin A by {Mo132 } glyconanocapsules--toward biomimetic hybrid multilayers.

Herein, we consider Müller's spherical, porous, anionic, molybdenum oxide based capsule, (NH4)42[{(Mo(VI))Mo(VI)5O21(H2O)6}12{Mo(V)2O4(CH3COO)}30]⋅10 CH3COONH4⋅300 H2O≡(NH4)42⋅1 a⋅crystal ingredients≡1, {Mo132}, as an effective sugar-decorated nanoplatform for multivalent lectin recognition. The ion-exchange of NH4(+) ions of 1 with cationic-sugars, D-mannose-ammonium chloride (2) or D-glucose-ammonium chloride (3) results in the formation of glyconanocapsules (NH4)(42-n)2n⋅1 a and (NH4)(42-m)3m⋅1 a. The Mannose (NH4)(42-n)2n⋅1 a capsules bind selectively Concanavalin A (Con A) in aqueous solution, giving an association avidity constant of K(a)(multi)=4.6×10(4) M(-1) and an enhancement factor of ß=K(a)(multi)/K(ass)(mono)=21.9, reminiscent of the formation of "glycoside clusters" on the external surface of glyconanocapsule. The glyconanocapsules (NH4)(42-n)2n⋅1 a and (NH4)(42-m)3m⋅1 a self-assemble in "hybrid multilayers" by successive layer-by-layer deposition of (NH4)(42-n)2n⋅1 a or (NH4)(42-m)3m⋅1 a and Con A. These architectures, reminiscent of versatile mimics of artificial tissues, can be easily prepared and quantified by using quartz crystal microgravimetry (QCM). The "biomimetic hybrid multilayers" described here are stable under a continual water flow and they may serve as artificial networks for a greater depth of understanding of various biological mechanisms, which can directly benefit the fields of chemical separations, sensors or storage-delivery devices.