Haptic metal spinning

Sheet metal spinning is an incremental forming technique practiced for a long time only by experienced, skilled craftsmen. Over the last sixty years, attempts have been made to automate the process, but today the industrial practice still relies heavily on the skill of experienced operators. Complete analytical solutions to predict workpiece failure based on the path of the tool are not available, and finite element simulations of the process are too time-intensive to be of practical use for online toolpath correction. Therefore, today the design of toolpaths to avoid failure in spinning remains an art acquired by practice. In this paper, we approach the issue by designing an enhanced teach-in/playback system. We connect a haptic device to a CNC spinning machine; this device allows a human operator to control the working roller manually while feeling the force applied to the workpiece. Position, force and workpiece shape sensors allow collecting information on the toolpath followed by the operator and on its influence over the mechanics of the process. The opportunities offered by this system to derive rules for toolpath design are explored in two case studies on force control and wrinkling recovery, with new insights on the relationship between toolpaths and failure. A research agenda is outlined to exploit the full potential of haptic metal spinning

Development of HIV-1 rectal-specific microbicides and colonic tissue evaluation

The gastrointestinal tract is structurally and functionally different from the vagina. Thus, the paradigm of topical microbicide development and evaluation has evolved to include rectal microbicides (RMs). Our interest was to create unique RM formulations to safely and effectively deliver antiretroviral drugs to mucosal tissue. RMs were designed to include those that spread and coat all surfaces of the rectum and distal colon rapidly (liquid) and those that create a deformable, erodible barrier and remain localized at the administration site (gel). Tenofovir (TFV) (1%) was formulated as an aqueous thermoreversible fluid and a carbopol-based aqueous hydrogel. Lipid-based liquid and gel formulations were prepared for UC781 (0.1%) using isopropyl myristate and GTCC (Caprylic/Capric Triglycerides), respectively. Formulations were characterized for pH, viscosity, osmolality, and drug content. Pre-clinical testing incorporated ex vivo colonic tissue obtained through surgical resections and flexible sigmoidoscopy (flex sig). As this was the first time using tissue from both sources side-by-side, the ability to replicate HIV-1 was compared. Efficacy of the RM formulations was tested by applying the products with HIV-1 directly to polarized colonic tissue and following viral replication. Safety of the formulations was determined by MTT assay and histology. All products had a neutral pH and were isoosmolar. While HIV-1BaL and HIV-1 JR-CSF alone and in the presence of semen had similar replication trends between surgically resected and flex sig tissues, the magnitude of viral replication was significantly better in flex sig tissues. Both TFV and UC781 formulations protected the colonic tissue, regardless of tissue source, from HIV-1 and retained tissue viability and architecture. Our in vitro and ex vivo results show successful formulation of unique RMs. Moreover, the results of flex sig and surgically resected tissues were comparable suggesting the incorporation of both in pre-clinical testing algorithms. © 2014 Dezzutti et al

Fear and Courage in Children: Two Sides of the Same Coin?

This study further investigated the construct of courage in children. Children aged 8–13 years (n = 51) were interviewed about the most courageous action that they had ever performed during their life, and to retrospectively rate their level of fear and courage experienced during that event. On a separate occasion, children also completed the Courage Measure for Children (CM-C) as an index of children’s general level of personal courage, as well as scales for assessing anxiety symptoms and sensation seeking. Results indicated that almost all children (i.e., 94%) indicated that they had carried out a courageous action at some point during their life, although the levels of fear and courage associated with these acts varied considerably. Further, there was no relation between fear and courage reported for the courageous action, but these variables were significantly correlated with respectively anxiety symptoms and personal courage as indexed by the CM-C. Finally, a significant positive correlation was observed between sensation seeking and personal courage, indicating that children who are more thrill and adventure seeking are generally also more courageous. It is concluded that fear and courage in children are largely unrelated and not just two sides of the same coin. The implications of these results for the etiology and treatment of childhood anxiety problems are discussed

Targeted DNA methylation by homology-directed repair in mammalian cells. Transcription reshapes methylation on the repaired gene.

We report that homology-directed repair of a DNA double-strand break within a single copy Green Fluorescent Protein (GFP) gene in HeLa cells alters the methylation pattern at the site of recombination. DNA methyl transferase (DNMT)1, DNMT3a and two proteins that regulate methylation, Np95 and GADD45A, are recruited to the site of repair and are responsible for selective methylation of the promoter-distal segment of the repaired DNA. The initial methylation pattern of the locus is modified in a transcription-dependent fashion during the 15\u201320 days following repair, at which time no further changes in the methylation pattern occur. The variation in DNA modification generates stable clones with wide ranges of GFP expression. Collectively, our data indicate that somatic DNA methylation follows homologous repair and is subjected to remodeling by local transcription in a discrete time window during and after the damage. We propose that DNA methylation of repaired genes represents a DNA damage code and is source of variation of gene expression

Phase separation and suppression of critical dynamics at quantum transitions of itinerant magnets: MnSi and (Sr1−x_{1-x}Cax_{x})RuO3_{3}

Quantum phase transitions (QPTs) have been studied extensively in correlated electron systems. Characterization of magnetism at QPTs has, however, been limited by the volume-integrated feature of neutron and magnetization measurements and by pressure uncertainties in NMR studies using powderized specimens. Overcoming these limitations, we performed muon spin relaxation ($\mu$SR) measurements which have a unique sensitivity to volume fractions of magnetically ordered and paramagnetic regions, and studied QPTs from itinerant heli/ferro magnet to paramagnet in MnSi (single-crystal; varying pressure) and (Sr$_{1-x}$Ca$_{x}$)RuO$_{3}$ (ceramic specimens; varying $x$). Our results provide the first clear evidence that both cases are associated with spontaneous phase separation and suppression of dynamic critical behavior, revealed a slow but dynamic character of the ``partial order'' diffuse spin correlations in MnSi above the critical pressure, and, combined with other known results in heavy-fermion and cuprate systems, suggest a possibility that a majority of QPTs involve first-order transitions and/or phase separation.Comment: 11 pages, 4 figures, 21 authors, to appear in Nature Physic

Spacelike Singularities and Hidden Symmetries of Gravity

We review the intimate connection between (super-)gravity close to a spacelike singularity (the "BKL-limit") and the theory of Lorentzian Kac-Moody algebras. We show that in this limit the gravitational theory can be reformulated in terms of billiard motion in a region of hyperbolic space, revealing that the dynamics is completely determined by a (possibly infinite) sequence of reflections, which are elements of a Lorentzian Coxeter group. Such Coxeter groups are the Weyl groups of infinite-dimensional Kac-Moody algebras, suggesting that these algebras yield symmetries of gravitational theories. Our presentation is aimed to be a self-contained and comprehensive treatment of the subject, with all the relevant mathematical background material introduced and explained in detail. We also review attempts at making the infinite-dimensional symmetries manifest, through the construction of a geodesic sigma model based on a Lorentzian Kac-Moody algebra. An explicit example is provided for the case of the hyperbolic algebra E10, which is conjectured to be an underlying symmetry of M-theory. Illustrations of this conjecture are also discussed in the context of cosmological solutions to eleven-dimensional supergravity.Comment: 228 pages. Typos corrected. References added. Subject index added. Published versio

Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology

Regulation of Arpc3 by miRNA alters dendritic spine morphology

Neurogenomic Evidence for a Shared Mechanism of the Antidepressant Effects of Exercise and Chronic Fluoxetine in Mice

Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant interventions. We studied three groups of mice: mice treated with a widely used antidepressant drug – fluoxetine, mice engaged in voluntary exercise, and mice living in an enriched environment. The hippocampi of treated mice were investigated at the molecular and cellular levels. Mice treated with fluoxetine and mice who exercised daily showed, not only similar antidepressant behavior, but also similar changes in gene expression and hippocampal neurons. These changes were not observed in mice with environmental enrichment. An increase in neurogenesis and dendritic spine density was observed following four weeks of fluoxetine treatment and voluntary exercise. A weighted gene co-expression network analysis revealed four different modules of co-expressed genes that were correlated with the antidepressant effect. This network analysis enabled us to identify genes involved in the molecular pathways underlying the effects of fluoxetine and exercise. The existence of both neuronal and gene expression changes common to antidepressant drug and exercise suggests a shared mechanism underlying their effect. Further studies of these findings may be used to uncover the molecular mechanisms of depression, and to identify new avenues of therapy