Giant electrocaloric effect around Tc_c

We use molecular dynamics with a first-principles-based shell model potential to study the electrocaloric effect (ECE) in lithium niobate, LiNbO$_3$, and find a giant electrocaloric effect along a line passing through the ferroelectric transition. With applied electric field, a line of maximum ECE passes through the zero field ferroelectric transition, continuing along a Widom line at high temperatures with increasing field, and along the instability that leads to homogeneous ferroelectric switching below $T_c$ with an applied field antiparallel to the spontaneous polarization. This line is defined as the minimum in the inverse capacitance under applied electric field. We investigate the effects of pressure, temperature and applied electric field on the ECE. The behavior we observe in LiNbO$_3$ should generally apply to ferroelectrics; we therefore suggest that the operating temperature for refrigeration and energy scavenging applications should be above the ferroelectric transition region to obtain large electrocaloric response. We find a relationship among $T_c$, the Widom line and homogeneous switching that should be universal among ferroelectrics, relaxors, multiferroics, and the same behavior should be found under applied magnetic fields in ferromagnets.Comment: 5 page

First passage time exponent for higher-order random walks:Using Levy flights

We present a heuristic derivation of the first passage time exponent for the integral of a random walk [Y. G. Sinai, Theor. Math. Phys. {\bf 90}, 219 (1992)]. Building on this derivation, we construct an estimation scheme to understand the first passage time exponent for the integral of the integral of a random walk, which is numerically observed to be $0.220\pm0.001$. We discuss the implications of this estimation scheme for the $n{\rm th}$ integral of a random walk. For completeness, we also address the $n=\infty$ case. Finally, we explore an application of these processes to an extended, elastic object being pulled through a random potential by a uniform applied force. In so doing, we demonstrate a time reparameterization freedom in the Langevin equation that maps nonlinear stochastic processes into linear ones.Comment: 4 figures, submitted to PR

Modifying the Symbolic Aggregate Approximation Method to Capture Segment Trend Information

The Symbolic Aggregate approXimation (SAX) is a very popular symbolic dimensionality reduction technique of time series data, as it has several advantages over other dimensionality reduction techniques. One of its major advantages is its efficiency, as it uses precomputed distances. The other main advantage is that in SAX the distance measure defined on the reduced space lower bounds the distance measure defined on the original space. This enables SAX to return exact results in query-by-content tasks. Yet SAX has an inherent drawback, which is its inability to capture segment trend information. Several researchers have attempted to enhance SAX by proposing modifications to include trend information. However, this comes at the expense of giving up on one or more of the advantages of SAX. In this paper we investigate three modifications of SAX to add trend capturing ability to it. These modifications retain the same features of SAX in terms of simplicity, efficiency, as well as the exact results it returns. They are simple procedures based on a different segmentation of the time series than that used in classic-SAX. We test the performance of these three modifications on 45 time series datasets of different sizes, dimensions, and nature, on a classification task and we compare it to that of classic-SAX. The results we obtained show that one of these modifications manages to outperform classic-SAX and that another one slightly gives better results than classic-SAX.Comment: International Conference on Modeling Decisions for Artificial Intelligence - MDAI 2020: Modeling Decisions for Artificial Intelligence pp 230-23

Optogenetic Peripheral Nerve Immunogenicity

Optogenetic technologies have been the subject of great excitement within the scientific community for their ability to demystify complex neurophysiological pathways in the central (CNS) and peripheral nervous systems (PNS). The excitement surrounding optogenetics has also extended to the clinic with a trial for ChR2 in the treatment of retinitis pigmentosa currently underway and additional trials anticipated for the near future. In this work, we identify the cause of loss-of-expression in response to transdermal illumination of an optogenetically active peroneal nerve following an anterior compartment (AC) injection of AAV6-hSyn-ChR2(H134R) with and without a fluorescent reporter. Using Sprague Dawley Rag2−/− rats and appropriate controls, we discover optogenetic loss-of-expression is chiefly elicited by ChR2-mediated immunogenicity in the spinal cord, resulting in both CNS motor neuron death and ipsilateral muscle atrophy in both low and high Adeno-Associated Virus (AAV) dosages. We further employ pharmacological immunosuppression using a slow-release tacrolimus pellet to demonstrate sustained transdermal optogenetic expression up to 12 weeks. These results suggest that all dosages of AAV-mediated optogenetic expression within the PNS may be unsafe. Clinical optogenetics for both PNS and CNS applications should take extreme caution when employing opsins to treat disease and may require concurrent immunosuppression. Future work in optogenetics should focus on designing opsins with lesser immunogenicity.MIT Media Lab Consortiu

Structural Principles in Robo Activation and Auto-Inhibition

This is the author accepted manuscript. The final version is available from Elsevier (Cell Press) via the DOI in this record.Proper brain function requires high-precision neuronal expansion and wiring, processes controlled by the transmembrane Roundabout (Robo) receptor family and their Slit ligands. Despite their great importance, the molecular mechanism by which Robos’ switch from “off” to “on” states remains unclear. Here, we report a 3.6 Å crystal structure of the intact human Robo2 ectodomain (domains D1–8). We demonstrate that Robo cis dimerization via D4 is conserved through hRobo1, 2, and 3 and the C. elegans homolog SAX-3 and is essential for SAX-3 function in vivo. The structure reveals two levels of auto-inhibition that prevent premature activation: (1) cis blocking of the D4 dimerization interface and (2) trans interactions between opposing Robo receptors that fasten the D4-blocked conformation. Complementary experiments in mouse primary neurons and C. elegans support the auto-inhibition model. These results suggest that Slit stimulation primarily drives the release of Robo auto-inhibition required for dimerization and activation.ICRFIS

Depinning and plasticity of driven disordered lattices

We review in these notes the dynamics of extended condensed matter systesm, such as vortex lattices in type-II superconductors and charge density waves in anisotropic metals, driven over quenched disorder. We focus in particular on the case of strong disorder, where topological defects are generated in the driven lattice. In this case the repsonse is plastic and the depinning transition may become discontinuous and hysteretic.Comment: 21 pages, 6 figures. Proceedings the XIX Sitges Conference on Jamming, Yielding, and Irreversible Deformations in Condensed Matter, Sitges, Barcelona, Spain, June 14-18, 200

Reversed halo sign in pneumocystis pneumonia: a case report

<p>Abstract</p> <p>Background</p> <p>The reversed halo sign may sometimes be seen in patients with cryptogenic organizing pneumonia, but is rarely associated with other diseases.</p> <p>Case presentation</p> <p>We present a case study of a 32-year-old male patient with acquired immunodeficiency syndrome, who had previously been treated with chemotherapy for non-Hodgkin's lymphoma. A chest X-ray showed bilateral patchy infiltrates. High-resolution computed tomography revealed the reversed halo sign in both upper lobes. The patient was diagnosed with pneumocystis pneumonia, which was successfully treated with sulfamethoxazole trimethoprim; the reversed halo sign disappeared, leaving cystic lesions. Cases such as this one are rare, but show that the reversed halo sign may occur in patients who do not have cryptogenic organizing pneumonia.</p> <p>Conclusion</p> <p>Physicians can avoid making an incorrect diagnosis and prescribing the wrong treatment by carefully evaluating all clinical criteria rather than assuming that the reversed halo sign only occurs with cryptogenic organizing pneumonia.</p

Deterrence in Cyberspace: An Interdisciplinary Review of the Empirical Literature

The popularity of the deterrence perspective across multiple scientific disciplines has sparked a lively debate regarding its relevance in influencing both offenders and targets in cyberspace. Unfortunately, due to the invisible borders between academic disciplines, most of the published literature on deterrence in cyberspace is confined within unique scientific disciplines. This chapter therefore provides an interdisciplinary review of the issue of deterrence in cyberspace. It begins with a short overview of the deterrence perspective, presenting the ongoing debates concerning the relevance of deterrence pillars in influencing cybercriminals’ and cyberattackers’ operations in cyberspace. It then reviews the existing scientific evidence assessing various aspects of deterrence in the context of several disciplines: criminology, law, information systems, and political science. This chapter ends with a few policy implications and proposed directions for future interdisciplinary academic research

A demonstration of cone function plasticity after gene therapy in achromatopsia

Recent advances in regenerative therapy have placed the treatment of previously incurable eye diseases within arms’ reach. Achromatopsia is a severe monogenic heritable retinal disease that disrupts cone function from birth, leaving patients with complete colour blindness, low acuity, photosensitivity and nystagmus. While successful gene-replacement therapy in non-primate models of achromatopsia has raised widespread hopes for clinical treatment, it was yet to be determined if and how these therapies can induce new cone function in the human brain. Using a novel multimodal approach, we demonstrate for the first time that gene therapy can successfully activate dormant cone-mediated pathways in children with achromatopsia (CNGA3- and CNGB3-associated, 10–15 years). To test this, we combined functional MRI population receptive field mapping and psychophysics with stimuli that selectively measure cone photoreceptor signalling. We measured cortical and visual cone function before and after gene therapy in four paediatric patients, evaluating treatment-related change against benchmark data from untreated patients (n = 9) and normal-sighted participants (n = 28). After treatment, two of the four children displayed strong evidence for novel cone-mediated signals in visual cortex, with a retinotopic pattern that was not present in untreated achromatopsia and which is highly unlikely to emerge by chance. Importantly, this change was paired with a significant improvement in psychophysical measures of cone-mediated visual function. These improvements were specific to the treated eye, and provide strong evidence for successful read-out and use of new cone-mediated information. These data show for the first time that gene replacement therapy in achromatopsia within the plastic period of development can awaken dormant cone-signalling pathways after years of deprivation. This reveals unprecedented neural plasticity in the developing human nervous system and offers great promise for emerging regenerative therapies