(Un)ChARTED Cartographies: Networked Avatars and Augmented Reality

(Un)Charted engages assessment by redefining and expanding the boundaries of the chart or checklist to the charting of a networked path through de-territorialization/re-terriotorialization. This article discusses cartography as the creation of learning maps of a networked territory by the performance of networked avatars. The term avatar is expanded beyond the concept of the digital avatar and into the realm of any incarnation of the virtual in visualized/tangible form. Through analysis of video reflections as student avatars, the learning map reveals growth over time. Specific examples of student and teacher avatars are analyzed as a way of engaging in the process of becoming through the creation of a network of learning that is ChARTED through engagement

‘Image’ / ‘I’ / ‘Nation’: A Cultural Mash-Up

The term Un(precedent)ED conjures ‘images’ that have never been seen before in education. Too often in the classroom we focus on the classification of objects and practices. The metaphysical question “what is?” is important only in that it must be continually revisited. Through continual re-visitation, the question becomes “what can it be?” Unfortunately, the process of becoming through imagination is a practice that is often relegated to childish whimsy. Un(precedent)ED practice requires the (re)imaging of the current apparatus of education. Precedent is a standard or model that comes before a particular event or moment; components, such as sound, written text, sight, and thought, are pieced together to create the event or moment that collapses in on itself to create the ‘images.’ Precedent, as it will be described in the following pages, refers to the construction of myth perpetuated by ‘images.’ The ‘image’ in imagination is “more than that which the idealist calls a representation, but less than that which the realist calls a thing” (Bergson, 2004, p. vii). We are immersed in a spectacle culture in which ‘images’ transform and become reality. Therefore, tremendous power lies in the ability to facilitate the use of one’s imagination to (re)interpret, (re)(con)textualize, and (re)define. Such practices become a mash-up of cultural understanding in which dominant discourses are remixed. These new imaginings require work and a belief that change can occur. Transformation or change is not a task that one should undergo without the realization that such change will require a tremendous amount of effort - physical, mental, and emotional. The purpose of this paper is to (re)imagine literacy practice based on the layering effects already taking place within our technologically driven culture. Through the process of remix, the apparatus of social interaction (i.e. literacy) becomes transformed. The ability to imagine something greater than that which preexists allows for the invention of new modes of practice in teaching and learning in the public school setting (Barthes, 1974; Debord, 1994; Derrida, 1976; Foucault, 1978; Garoian & Gaudelius, 2008)

"image"/ "i" / "nation": A Theory and Practice of Becoming an A/r/tographer

One can argue that embracing technological models may produce students who are illiterate in the "proper" methods of communication. With rapid technological change, some fear traditions in their "original" form may be lost. Practices such as trying to recapture the artist's intent should be abandoned as a way of opening up literacy discourse to multiple narratives. Failing to critically explore the possibilities of emerging models of thinking, teaching, and learning in a technological culture can produce a loss equal to the loss of tradition. An a/r/tographer works toward a fluid practice between the domains of artist, researcher, and teacher in order to negotiate emerging forms of visual/tactile/auditory communication which include the body as a networked organism situated recursively within the larger structure of society. This study occurred during two separate semesters of an art education course for pre-service elementary teachers. Through interaction with hypermedia, social networking, installation art, and mash-ups, the teacher and students became artists, researchers, and teachers in a community of practice. A new form of teaching practice was envisioned that opens the possibility for both collective and individual understandings in the formation of curricula. A set of guiding principles was invented through practice as a way of producing a deeper understanding of culture and self. The following principles were derived from engagement with emerging technologies: Inion, Flip the Script, (H)Activation, Sample, (Re)mix, and Avatar. (H)Activation produces a learning environment that disrupts the flow of teaching, learning, literacy, art, technology, etc., as a way of programming practice for the inclusion of multiple narratives. Utilizing bricolage or a Do It Yourself approach, an apparatus for programming emerged, "image"/"i"/"nation". The term "image"/"i"/"nation" is a play on the concept of the imagination. Through reflexive application the imagination is split allowing connections and disconnections through practice. By engaging in its application the teacher and students became better able to formulate new ways of negotiating curricula, literacy practice, and artistic production

Discovery of Aryl Sulfonamides as Isoform-Selective Inhibitors of Na_V1.7 with Efficacy in Rodent Pain Models

We report on a novel series of aryl sulfonamides that act as nanomolar potent, isoform-selective inhibitors of the human sodium channel hNa_V1.7. The optimization of these inhibitors is described. We aimed to improve potency against hNa_V1.7 while minimizing off-target safety concerns and generated compound <b>3</b>. This agent displayed significant analgesic effects in rodent models of acute and inflammatory pain and demonstrated that binding to the voltage sensor domain 4 site of Na_V1.7 leads to an analgesic effect <i>in vivo</i>. Our findings corroborate the importance of hNa_V1.7 as a drug target for the treatment of pain

Discovery of Novel PI3-Kinase δ Specific Inhibitors for the Treatment of Rheumatoid Arthritis: Taming CYP3A4 Time-Dependent Inhibition

PI3Kδ is a lipid kinase and a member of a larger family of enzymes, PI3K class IA­(α, β, δ) and IB (γ), which catalyze the phosphorylation of PIP2 to PIP3. PI3Kδ is mainly expressed in leukocytes, where it plays a critical, nonredundant role in B cell receptor mediated signaling and provides an attractive opportunity to treat diseases where B cell activity is essential, e.g., rheumatoid arthritis. We report the discovery of novel, potent, and selective PI3Kδ inhibitors and describe a structural hypothesis for isoform (α, β, γ) selectivity gained from interactions in the affinity pocket. The critical component of our initial pharmacophore for isoform selectivity was strongly associated with CYP3A4 time-dependent inhibition (TDI). We describe a variety of strategies and methods for monitoring and attenuating TDI. Ultimately, a structure-based design approach was employed to identify a suitable structural replacement for further optimization

Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of <i>N</i>‑([1,2,4]Triazolo[4,3‑<i>a</i>]pyridin-3-yl)methane-sulfonamides as Potent and Selective <i>h</i>Na_V1.7 Inhibitors for the Treatment of Pain

The sodium channel Na_V1.7 has emerged as a promising target for the treatment of pain based on strong genetic validation of its role in nociception. In recent years, a number of aryl and acyl sulfonamides have been reported as potent inhibitors of Na_V1.7, with high selectivity over the cardiac isoform Na_V1.5. Herein, we report on the discovery of a novel series of <i>N</i>-([1,2,4]­triazolo­[4,3-<i>a</i>]­pyridin-3-yl)­methanesulfonamides as selective Na_V1.7 inhibitors. Starting with the crystal structure of an acyl sulfonamide, we rationalized that cyclization to form a fused heterocycle would improve physicochemical properties, in particular lipophilicity. Our design strategy focused on optimization of potency for block of Na_V1.7 and human metabolic stability. Lead compounds <b>10</b>, <b>13</b> (GNE-131), and <b>25</b> showed excellent potency, good <i>in vitro</i> metabolic stability, and low <i>in vivo</i> clearance in mouse, rat, and dog. Compound <b>13</b> also displayed excellent efficacy in a transgenic mouse model of induced pain

Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of <i>N</i>‑([1,2,4]Triazolo[4,3‑<i>a</i>]pyridin-3-yl)methane-sulfonamides as Potent and Selective <i>h</i>Na_V1.7 Inhibitors for the Treatment of Pain

The sodium channel Na_V1.7 has emerged as a promising target for the treatment of pain based on strong genetic validation of its role in nociception. In recent years, a number of aryl and acyl sulfonamides have been reported as potent inhibitors of Na_V1.7, with high selectivity over the cardiac isoform Na_V1.5. Herein, we report on the discovery of a novel series of <i>N</i>-([1,2,4]­triazolo­[4,3-<i>a</i>]­pyridin-3-yl)­methanesulfonamides as selective Na_V1.7 inhibitors. Starting with the crystal structure of an acyl sulfonamide, we rationalized that cyclization to form a fused heterocycle would improve physicochemical properties, in particular lipophilicity. Our design strategy focused on optimization of potency for block of Na_V1.7 and human metabolic stability. Lead compounds <b>10</b>, <b>13</b> (GNE-131), and <b>25</b> showed excellent potency, good <i>in vitro</i> metabolic stability, and low <i>in vivo</i> clearance in mouse, rat, and dog. Compound <b>13</b> also displayed excellent efficacy in a transgenic mouse model of induced pain