Nanoengineering Neural Stem Cells on Biomimetic Substrates Using Magnetofection Technology

Tissue engineering studies are witnessing a major paradigm shift to cell culture on biomimetic materials that replicate native tissue features from which the cells are derived. Few studies have been performed in this regard for neural cells, particularly in nanomedicine. For example, platforms such as magnetic nanoparticles (MNPs) have proven efficient as multifunctional tools for cell tracking and genetic engineering of neural transplant populations. However, as far as we are aware, all current studies have been conducted using neural cells propagated on non-neuromimetic substrates that fail to represent the mechano-elastic properties of brain and spinal cord microenvironments. Accordingly, it can be predicted that such data is of less translational and physiological relevance than that derived from cells grown in neuromimetic environments. Therefore, we have performed the first test of magnetofection technology (enhancing MNP delivery using applied magnetic fields with significant potential for therapeutic application) and its utility in genetically engineering neural stem cells (NSCs; a population of high clinical relevance) propagated in biomimetic hydrogels. We demonstrate magnetic field application safely enhances MNP mediated transfection of NSCs grown as 3D spheroid structures in collagen which more closely replicates the intrinsic mechanical and structural properties of neural tissue than routinely used hard substrates. Further, as it is well known that MNP uptake is mediated by endocytosis we also investigated NSC membrane activity grown on both soft and hard substrates. Using high resolution scanning electron microscopy we were able to prove that NSCs display lower levels of membrane activity on soft substrates compared to hard, a finding which could have particular impact on MNP mediated engineering strategies of cells propagated in physiologically relevant systems

Editorial: crime patterns in time and space: the dynamics of crime opportunities in urban areas

The routine activity approach and associated crime pattern theory emphasise how crime emerges from spatio-temporal routines. In order to understand this crime should be studied in both space and time. However, the bulk of research into crime patterns and related activities has investigated the spatial distributions of crime, neglecting the temporal dimension. Specifically, disaggregation of crime by place and by time, for example hour of day, day of week, month of year, season, or school day versus none school day, is extremely relevant to theory. Modern data make such spatio-temporal disaggregation increasingly feasible, as exemplified in this special issue. First, much larger data files allow disaggregation of crime data into temporal and spatial slices. Second, new forms of data are generated by modern technologies, allowing innovative and new forms of analyses. Crime pattern analyses and routine activity inquiries are now able to explore avenues not previously available. The unique collection of nine papers in this thematic issue specifically examine spatio-temporal patterns of crime to; demonstrate the value of this approach for advancing knowledge in the field; consider how this informs our theoretical understanding of the manifestations of crime in time and space; to consider the prevention implications of this; and to raise awareness of the need for further spatio-temporal research into crime event

Optimal search strategies for identifying sound clinical prediction studies in EMBASE

BACKGROUND: Clinical prediction guides assist clinicians by pointing to specific elements of the patient's clinical presentation that should be considered when forming a diagnosis, prognosis or judgment regarding treatment outcome. The numbers of validated clinical prediction guides are growing in the medical literature, but their retrieval from large biomedical databases remains problematic and this presents a barrier to their uptake in medical practice. We undertook the systematic development of search strategies ("hedges") for retrieval of empirically tested clinical prediction guides from EMBASE. METHODS: An analytic survey was conducted, testing the retrieval performance of search strategies run in EMBASE against the gold standard of hand searching, using a sample of all 27,769 articles identified in 55 journals for the 2000 publishing year. All articles were categorized as original studies, review articles, general papers, or case reports. The original and review articles were then tagged as 'pass' or 'fail' for methodologic rigor in the areas of clinical prediction guides and other clinical topics. Search terms that depicted clinical prediction guides were selected from a pool of index terms and text words gathered in house and through request to clinicians, librarians and professional searchers. A total of 36,232 search strategies composed of single and multiple term phrases were trialed for retrieval of clinical prediction studies. The sensitivity, specificity, precision, and accuracy of search strategies were calculated to identify which were the best. RESULTS: 163 clinical prediction studies were identified, of which 69 (42.3%) passed criteria for scientific merit. A 3-term strategy optimized sensitivity at 91.3% and specificity at 90.2%. Higher sensitivity (97.1%) was reached with a different 3-term strategy, but with a 16% drop in specificity. The best measure of specificity (98.8%) was found in a 2-term strategy, but with a considerable fall in sensitivity to 60.9%. All single term strategies performed less well than 2- and 3-term strategies. CONCLUSION: The retrieval of sound clinical prediction studies from EMBASE is supported by several search strategies

Schr\"odinger Deformations of AdS_3 x S^3

We study Schr\"odinger invariant deformations of the AdS_3 x S^3 x T^4 (or K3) solution of IIB supergravity and find a large class of solutions with integer and half-integer dynamical exponents. We analyze the supersymmetries preserved by our solutions and find an infinite number of solutions with four supersymmetries. We study the solutions holographically and find that the dual D1-D5 (or F1-NS5) CFT is deformed by irrelevant operators of spin one and two.Comment: 23 page

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

Fermions and Type IIB Supergravity On Squashed Sasaki-Einstein Manifolds

We discuss the dimensional reduction of fermionic modes in a recently found class of consistent truncations of type IIB supergravity compactified on squashed five-dimensional Sasaki-Einstein manifolds. We derive the lower dimensional equations of motion and effective action, and comment on the supersymmetry of the resulting theory, which is consistent with N=4 gauged supergravity in $d=5$, coupled to two vector multiplets. We compute fermion masses by linearizing around two $AdS_{5}$ vacua of the theory: one that breaks N=4 down to N=2 spontaneously, and a second one which preserves no supersymmetries. The truncations under consideration are noteworthy in that they retain massive modes which are charged under a U(1) subgroup of the $R$-symmetry, a feature that makes them interesting for applications to condensed matter phenomena via gauge/gravity duality. In this light, as an application of our general results we exhibit the coupling of the fermions to the type IIB holographic superconductor, and find a consistent further truncation of the fermion sector that retains a single spin-1/2 mode.Comment: 43 pages, 2 figures, PDFLaTeX; v2: added references, typos corrected, minor change

Global aspects of the space of 6D N = 1 supergravities

We perform a global analysis of the space of consistent 6D quantum gravity theories with N = 1 supersymmetry, including models with multiple tensor multiplets. We prove that for theories with fewer than T = 9 tensor multiplets, a finite number of distinct gauge groups and matter content are possible. We find infinite families of field combinations satisfying anomaly cancellation and admitting physical gauge kinetic terms for T > 8. We find an integral lattice associated with each apparently-consistent supergravity theory; this lattice is determined by the form of the anomaly polynomial. For models which can be realized in F-theory, this anomaly lattice is related to the intersection form on the base of the F-theory elliptic fibration. The condition that a supergravity model have an F-theory realization imposes constraints which can be expressed in terms of this lattice. The analysis of models which satisfy known low-energy consistency conditions and yet violate F-theory constraints suggests possible novel constraints on low-energy supergravity theories.Comment: 41 pages, 1 figur

Enhanced Supersymmetry of Nonrelativistic ABJM Theory

We study the supersymmetry enhancement of nonrelativistic limits of the ABJM theory for Chern-Simons level $k=1,2$. The special attention is paid to the nonrelativistic limit (known as `PAAP' case) containing both particles and antiparticles. Using supersymmetry transformations generated by the monopole operators, we find additional 2 kinematical, 2 dynamical, and 2 conformal supercharges for this case. Combining with the original 8 kinematical supercharges, the total number of supercharges becomes maximal: 14 supercharges, like in the well-known PPPP limit. We obtain the corresponding super Schr\"odinger algebra which appears to be isomorphic to the one of the PPPP case. We also discuss the role of monopole operators in supersymmetry enhancement and partial breaking of supersymmetry in nonrelativistic limit of the ABJM theory.Comment: 22 pages, references added, version to appear in JHE

Childhood loneliness as a predictor of adolescent depressive symptoms: an 8-year longitudinal study

Childhood loneliness is characterised by children’s perceived dissatisfaction with aspects of their social relationships. This 8-year prospective study investigates whether loneliness in childhood predicts depressive symptoms in adolescence, controlling for early childhood indicators of emotional problems and a sociometric measure of peer social preference. 296 children were tested in the infant years of primary school (T1 5 years of age), in the upper primary school (T2 9 years of age) and in secondary school (T3 13 years of age). At T1, children completed the loneliness assessment and sociometric interview. Their teachers completed externalisation and internalisation rating scales for each child. At T2, children completed a loneliness assessment, a measure of depressive symptoms, and the sociometric interview. At T3, children completed the depressive symptom assessment. An SEM analysis showed that depressive symptoms in early adolescence (age 13) were predicted by reports of depressive symptoms at age 8, which were themselves predicted by internalisation in the infant school (5 years). The interactive effect of loneliness at 5 and 9, indicative of prolonged loneliness in childhood, also predicted depressive symptoms at age 13. Parent and peer-related loneliness at age 5 and 9, peer acceptance variables, and duration of parent loneliness did not predict depression. Our results suggest that enduring peer-related loneliness during childhood constitutes an interpersonal stressor that predisposes children to adolescent depressive symptoms. Possible mediators are discussed