Paranatural Category Theory

We establish and advocate for a novel branch of category theory, centered around strong dinatural transformations (herein known as "paranatural transformations"). Paranatural transformations generalize natural transformations to mixed-variant difunctors, but, unlike other such generalizations, are composable and exceptionally well-behaved. We define the category of difunctors and paranatural transformations, prove a novel "diYoneda Lemma" for this category, and explore some of the category-theoretic implications. We also develop three compelling uses for paranatural category theory: parametric polymorphism, impredicative encodings of (co)inductive types, and difunctor models of type theory. Paranatural transformations capture the essence of parametricity, with their "paranaturality condition" coinciding exactly with the "free theorem" of the corresponding polymorphic type; the paranatural analogue of the (co)end calculus provides an elegant and general framework for reasoning about initial algebras, terminal coalgebras, bisimulations, and representation independence; and "diYoneda reasoning" facilitates the lifting of Grothendieck universes into difunctor models of type theory. We develop these topics and propose further avenues of research

Extraction of Surface-Related Features in a Recurrent Model of V1-V2 Interactions

Humans can effortlessly segment surfaces and objects from two-dimensional (2D) images that are projections of the 3D world. The projection from 3D to 2D leads partially to occlusions of surfaces depending on their position in depth and on viewpoint. One way for the human visual system to infer monocular depth cues could be to extract and interpret occlusions. It has been suggested that the perception of contour junctions, in particular T-junctions, may be used as cue for occlusion of opaque surfaces. Furthermore, X-junctions could be used to signal occlusion of transparent surfaces.In this contribution, we propose a neural model that suggests how surface-related cues for occlusion can be extracted from a 2D luminance image. The approach is based on feedforward and feedback mechanisms found in visual cortical areas V1 and V2. In a first step, contours are completed over time by generating groupings of like-oriented contrasts. Few iterations of feedforward and feedback processing lead to a stable representation of completed contours and at the same time to a suppression of image noise. In a second step, contour junctions are localized and read out from the distributed representation of boundary groupings. Moreover, surface-related junctions are made explicit such that they are evaluated to interact as to generate surface-segmentations in static images. In addition, we compare our extracted junction signals with a standard computer vision approach for junction detection to demonstrate that our approach outperforms simple feedforward computation-based approaches.A model is proposed that uses feedforward and feedback mechanisms to combine contextually relevant features in order to generate consistent boundary groupings of surfaces. Perceptually important junction configurations are robustly extracted from neural representations to signal cues for occlusion and transparency. Unlike previous proposals which treat localized junction configurations as 2D image features, we link them to mechanisms of apparent surface segregation. As a consequence, we demonstrate how junctions can change their perceptual representation depending on the scene context and the spatial configuration of boundary fragments

Efficient and selective N-alkylation of amines with alcohols catalysed by manganese pincer complexes

Borrowing hydrogen (or hydrogen autotransfer) reactions represent straightforward and sustainable C-N bond-forming processes. In general, precious metal-based catalysts are employed for this effective transformation. In recent years, the use of earth abundant and cheap non-noble metal catalysts for this process attracted considerable attention in the scientific community. Here we show that the selective N-alkylation of amines with alcohols can be catalysed by defined PNP manganese pincer complexes. A variety of substituted anilines are monoalkylated with different (hetero)aromatic and aliphatic alcohols even in the presence of other sensitive reducible functional groups. As a special highlight, we report the chemoselective monomethylation of primary amines using methanol under mild conditions

Identification of a cytoplasmic motif in the erythropoietin receptor required for receptor internalization

AbstractErythropoietin (EPO) promotes the viability, proliferation and differentiation of mammalian erythroid progenitor cells via its specific cell surface receptor. The EPO receptor (EPO-R) is a member of the cytokine receptor superfamily and is comprised of one identified subunit which homodimerizes upon ligand binding. To study the role of the intracellular domain of the EPO-R in the endocytosis of EPO, we compared the rate and extent of 125I-EPO endocytosis by wild type (wt) EPO-R and five cytoplasmically truncated EPO-Rs: 1–251 EPO-R, 1–257 EPO-R, 1–267 EPO-R, 1–276 EPO-R and 1–306 EPO-R which contain 4, 10, 20, 29 or 59 amino acids of the cytoplasmic domain, respectively. We also studied an EPO-R mutant (PB) which lacks amino acid residues 281–300 of the cytoplasmic domain. The experiments were conducted in COS 7 cells transfected with the EPO-R cDNAs and in Ba/F3 cells stably expressing the wt EPO-R, 1–251 or 1–257 EPO-R. Cells expressing wt EPO-R, PB EPO-R (Δ281–300), 1–276 EPO-R or 1–306 EPO-R internalized approximately 50% of 125I-EPO bound to the cell surface, while cells expressing 1–251, 1–257 or 1–267 EPO-R internalized only 25% of the bound 125I-EPO. The steady-state expression levels of these latter receptors on the cell surface were typically 2–5-fold higher than wt EPO-R. Our data indicate that amino acid residues 267–276 (FEGLFTTHK) of the EPO-R cytoplasmic domain may have a role in receptor internalization. Metabolic labeling experiments suggest that in transiently transfected COS 7 cells most of the wt EPO-R and 1–257 EPO-Rs do not exit the ER and may be degraded there. The half-life of both receptors was essentially similar and was in the range of 1 h. In Ba/F3 cells the mature Golgi processed 1–257 EPO-R was more stable than the corresponding form of the wt EPO-R, possibly contributing to its higher cell surface expression

Sec16 alternative splicing dynamically controls COPII transport efficiency

The transport of secretory proteins from the endoplasmic reticulum (ER) to the Golgi depends on COPII-coated vesicles. While the basic principles of the COPII machinery have been identified, it remains largely unknown how COPII transport is regulated to accommodate tissue- or activation-specific differences in cargo load and identity. Here we show that activation-induced alternative splicing of Sec16 controls adaptation of COPII transport to increased secretory cargo upon T-cell activation. Using splice-site blocking morpholinos and CRISPR/Cas9-mediated genome engineering, we show that the number of ER exit sites, COPII dynamics and transport efficiency depend on Sec16 alternative splicing. As the mechanistic basis, we suggest the C-terminal Sec16 domain to be a splicing-controlled protein interaction platform, with individual isoforms showing differential abilities to recruit COPII components. Our work connects the COPII pathway with alternative splicing, adding a new regulatory layer to protein secretion and its adaptation to changing cellular environments

Rasch Analysis, Dimensionality, and Scoring of the Neuropsychiatric Inventory Irritability and Aggression Subscales in Individuals With Traumatic Brain Injury

Objectives To develop, for versions completed by individuals with traumatic brain injury (TBI) and an observer, a more precise metric for the Neuropsychiatric Inventory (NPI) Irritability and Aggression subscales using all behavioral item ratings for use with individuals with TBI and to address the dimensionality of the represented behavioral domains. Design Rasch and confirmatory factor analyses of retrospective baseline NPI data from 3 treatment studies. Setting Postacute rehabilitation clinic. Participants NPI records (N = 525) consisting of observer ratings (n = 287) and self-ratings (n = 238) by participants with complicated mild, moderate, or severe TBI at least 6 months postinjury. Interventions Not applicable. Main Outcome Measures Frequency and severity ratings from NPI Irritability/Lability and Agitation/Aggression subscales. Results Confirmatory factor analyses of both observer and participant ratings showed good fit for either a 1-factor or a 2-factor solution. Consistent with this, the Rasch model also fit the data well with aggression items indicating the more severe end of the construct and irritability items populating the milder end. Conclusions Irritability and aggression appear to represent different levels of severity of a single construct. The derived Rasch metric offers a measure of this construct based on responses to all specific items that is appropriate for parametric statistical analysis and may be useful in research and clinical assessments of individuals with TBI

Indiana Center for Brain Rehabilitation, Advanced Imaging, and Neuroscience (ICBRAIN): An IUPUI Signature Center Initiative

poster abstractThe Mission of the Indiana Center for Brain Rehabilitation, Advanced Imaging, and Neuroscience (ICBRAIN) is: to develop and disseminate techniques and methodologies for advanced neuroimaging and precision behavioral measurement to evaluate novel rehabilitation interventions for people with acquired brain injury. Traumatic and other types of acquired brain injury (ABI) affect millions of U.S. citizens each year, many of whom experience persistent disabilities. For example, among the estimated 1.4 million civilians who sustain a traumatic brain injury (TBI) each year, 50,000 die and a minimum of 80,000 sustain injuries of sufficient severity to require extended rehabilitation. The current conflicts in Iraq and Afghanistan have increased awareness and mobilized interest in medical treatment and rehabilitation for returning soldiers with TBI (designated as the “signature injury” of these conflicts). A 2008 study by the RAND corporation based on a random sample of 1,965 veterans estimated that, among 1.64 million returning veterans, approximately 320,000 experienced a probable TBI (19%). Over the past decade there has been a notable rise in research activities to address serious gaps in the knowledge base of ABI, including neuroimaging, outcome measurement, and intervention studies to change function. However, brain injury researchers have not yet established solid links between these research agendas. Such links are crucial for moving the evidence base forward to improve treatment outcomes. ICBRAIN will fill this gap in neuroscience by bringing together an interdisciplinary team of clinical researchers to (1) advance basic science and clinical knowledge to the next level of integration, (2) translate the knowledge gained directly into clinical care for improved patient outcomes, and (3) use the newly integrated knowledge to drive the leading edge of future research. ICBRAIN represents a unique collaboration among established clinical rehabilitation and measurement researchers in PM&R and at RHI and established researchers at the IU Center for Neuroimaging

The Suprafroth (Superconducting Froth)

The structure and dynamics of froths have been subjects of intense interest due to the desire to understand the behaviour of complex systems where topological intricacy prohibits exact evaluation of the ground state. The dynamics of a traditional froth involves drainage and drying in the cell boundaries, thus it is irreversible. We report a new member to the froths family: suprafroth, in which the cell boundaries are superconducting and the cell interior is normal phase. Despite very different microscopic origin, topological analysis of the structure of the suprafroth shows that statistical von Neumann and Lewis laws apply. Furthermore, for the first time in the analysis of froths there is a global measurable property, the magnetic moment, which can be directly related to the suprafroth structure. We propose that this suprafroth is a new, model system for the analysis of the complex physics of two-dimensional froths

„A nemzetközi” mint governmentalitás

A hagyományosan hatalomközpontú politikai elemzésben „a nemzetközi” (the international) az államok rendszerének sajátossága: anarchikus tér, amely minőségileg különbözik az államon belüli viszonyoktól. A normaközpontú iskola ezzel szemben egyre inkább a közös értékek allokációjának terepeként értelmezi, mely rokonságot mutat más politikai terekkel. Az irodalom ilyen kettéválása mellett a hatalomelemzés privilegizálása azzal jár, hogy elveszítjük képességünket „a nemzetközi” rendszerszintű változásának vizsgálatára, míg a normákra fókuszálva feláldozzuk a hatalom tanulmányozását. Meglátásunk szerint „a nemzetközi” ma létező konceptualizálásai (Webertől eredve) Morgenthautól származnak, akinél a fogalom az államok közötti tér ideáltípusát jelentette. Tanulmányunk Mike Williams munkásságára építve kínálja e két tudós koncepcióinak új olvasatát. Morgenthau azzal, hogy „a politikait” ideáltipikus szféraként azonosítja, lehetővé teszi a konstruktivista jellegű társadalomelméleti megfigyeléseket is. Speciális ideáltípusa azonban, melyet a nemzetközi politikára alkotott, eredeti weberi szempontjai alapján frissítésre szorul. Azzal próbálunk eleget tenni ennek a kihívásnak, hogy Michel Foucault elméletéből merítve megalkotjuk „a nemzetközi” olyan értelmezését, amely azt a governmentalitás társadalmilag beágyazott terepeként fogja fel. Olyan (hatalmi viszonyok által meghatározott) struktúraként, amely támogatja a (kormányzati racionalitásként meghatározott) politikai uralom különböző, változó gyakorlatait, valamint ágenciákat (például politikai intézményeket) generál