Utility of CRISPR/Cas9 systems in hematology research

Since the end of the 20th century, the development of novel approaches have emerged to manipulate experimental models of hematological disorders, so they would more accurately mirror what is observed in the clinic. Despite these technological advances, the characterization of crucial genes for benign or malignant hematological disorders remains challenging, mainly because of the dynamic nature of the hematopoietic system and the genetic heterogeneity of these disorders. To overcome this limitation, genome editing technologies have been developed to specifically manipulate the genome via deletion, insertion or modification of targeted loci. These technologies have swiftly progressed, allowing their common use to investigate genetic function in experimental hematology. Amongst them, homologous recombination (HR)-mediated targeting technologies have facilitated the manipulation of specific loci by generating knockout and knock-in models. Despite promoting significant advances in the understanding of the molecular mechanisms involved in hematology, these inefficient, time-consuming and labor-intensive approaches did not permit the development of cellular or animal models recapitulating the complexity of hematological disorders. In October 2016, Dr. Ben Ebert and Dr. Chad Cowan shared their knowledge and experiences with the utilization of CRISPR for models of myeloid malignancy, disease, and novel therapeutics. Here we provide an overview of the topics they covered including insights into the novel applications of the technique as well as its strengths and limitations

CUI@CSCW: Collaborating through Conversational User Interfaces

This virtual workshop seeks to bring together the burgeoning communities centred on the design, development, application and study of so-called Conversational User Interfaces (CUIs). CUIs are used in myriad contexts, from online support chatbots through to entertainment devices in the home. In this workshop, we will examine the challenges involved in transforming CUIs into everyday computing devices capable of supporting collaborative activities across space and time. Additionally, this workshop seeks to establish a cohesive CUI community and research agenda within CSCW. We will examine the roles in which CSCW research can contribute insights into understanding how CUIs are or can be used in a variety of settings, from public to private, and how they can be brought into a potentially unlimited number of tasks. This proposed workshop will bring together researchers from academia and practitioners from industry to survey the state-of-the-art in terms of CUI design, use, and understanding, and will map new areas for work including addressing the technical, social, and ethical challenges that lay ahead. By bringing together existing researchers and new ideas in this space, we intend to foster a strong community and enable potential future collaborations

Constraints on the Atmospheric Circulation and Variability of the Eccentric Hot Jupiter XO-3b

We report secondary eclipse photometry of the hot Jupiter XO-3b in the 4.5~$\mu$m band taken with the Infrared Array Camera (IRAC) on the Spitzer Space Telescope. We measure individual eclipse depths and center of eclipse times for a total of twelve secondary eclipses. We fit these data simultaneously with two transits observed in the same band in order to obtain a global best-fit secondary eclipse depth of $0.1580\pm 0.0036\%$ and a center of eclipse phase of $0.67004\pm 0.00013$. We assess the relative magnitude of variations in the dayside brightness of the planet by measuring the size of the residuals during ingress and egress from fitting the combined eclipse light curve with a uniform disk model and place an upper limit of 0.05$\%$. The new secondary eclipse observations extend the total baseline from one and a half years to nearly three years, allowing us to place an upper limit on the periastron precession rate of $2.9\times 10^{-3}$ degrees/day the tightest constraint to date on the periastron precession rate of a hot Jupiter. We use the new transit observations to calculate improved estimates for the system properties, including an updated orbital ephemeris. We also use the large number of secondary eclipses to obtain the most stringent limits to date on the orbit-to-orbit variability of an eccentric hot Jupiter and demonstrate the consistency of multiple-epoch Spitzer observations.Comment: 14 pages, 11 figures, published by Ap

Three-dimensional dielectric photonic crystal structures for laser-driven acceleration

We present the design and simulation of a three-dimensional photonic crystal waveguide for linear laser-driven acceleration in vacuum. The structure confines a synchronous speed-of-light accelerating mode in both transverse dimensions. We report the properties of this mode, including sustainable gradient and optical-to-beam efficiency. We present a novel method for confining a particle beam using optical fields as focusing elements. This technique, combined with careful structure design, is shown to have a large dynamic aperture and minimal emittance growth, even over millions of optical wavelengths

Ultrafast Mid-IR Laser Scalpel: Protein Signals of the Fundamental Limits to Minimally Invasive Surgery

Lasers have in principle the capability to cut at the level of a single cell, the fundamental limit to minimally invasive procedures and restructuring biological tissues. To date, this limit has not been achieved due to collateral damage on the macroscale that arises from thermal and shock wave induced collateral damage of surrounding tissue. Here, we report on a novel concept using a specifically designed Picosecond IR Laser (PIRL) that selectively energizes water molecules in the tissue to drive ablation or cutting process faster than thermal exchange of energy and shock wave propagation, without plasma formation or ionizing radiation effects. The targeted laser process imparts the least amount of energy in the remaining tissue without any of the deleterious photochemical or photothermal effects that accompanies other laser wavelengths and pulse parameters. Full thickness incisional and excisional wounds were generated in CD1 mice using the Picosecond IR Laser, a conventional surgical laser (DELight Er:YAG) or mechanical surgical tools. Transmission and scanning electron microscopy showed that the PIRL laser produced minimal tissue ablation with less damage of surrounding tissues than wounds formed using the other modalities. The width of scars formed by wounds made by the PIRL laser were half that of the scars produced using either a conventional surgical laser or a scalpel. Aniline blue staining showed higher levels of collagen in the early stage of the wounds produced using the PIRL laser, suggesting that these wounds mature faster. There were more viable cells extracted from skin using the PIRL laser, suggesting less cellular damage. β-catenin and TGF-β signalling, which are activated during the proliferative phase of wound healing, and whose level of activation correlates with the size of wounds was lower in wounds generated by the PIRL system. Wounds created with the PIRL systsem also showed a lower rate of cell proliferation. Direct comparison of wound healing responses to a conventional surgical laser, and standard mechanical instruments shows far less damage and near absence of scar formation by using PIRL laser. This new laser source appears to have achieved the long held promise of lasers in minimally invasive surgery

3.6 and 4.5 μ\mum Spitzer{\it Spitzer} Phase Curves of the Highly-Irradiated Hot Jupiters WASP-19b and HAT-P-7b

We analyze full-orbit phase curve observations of the transiting hot Jupiters WASP-19b and HAT-P-7b at 3.6 and 4.5 $\mu$m obtained using the Spitzer Space Telescope. For WASP-19b, we measure secondary eclipse depths of $0.485\%\pm 0.024\%$ and $0.584\%\pm 0.029\%$ at 3.6 and 4.5 $\mu$m, which are consistent with a single blackbody with effective temperature $2372 \pm 60$ K. The measured 3.6 and 4.5 $\mu$m secondary eclipse depths for HAT-P-7b are $0.156\%\pm 0.009\%$ and $0.190\%\pm 0.006\%$, which are well-described by a single blackbody with effective temperature $2667\pm 57$ K. Comparing the phase curves to the predictions of one-dimensional and three-dimensional atmospheric models, we find that WASP-19b's dayside emission is consistent with a model atmosphere with no dayside thermal inversion and moderately efficient day-night circulation. We also detect an eastward-shifted hotspot, suggesting the presence of a superrotating equatorial jet. In contrast, HAT-P-7b's dayside emission suggests a dayside thermal inversion and relatively inefficient day-night circulation; no hotspot shift is detected. For both planets, these same models do not agree with the measured nightside emission. The discrepancies in the model-data comparisons for WASP-19b might be explained by high-altitude silicate clouds on the nightside and/or high atmospheric metallicity, while the very low 3.6 $\mu$m nightside planetary brightness for HAT-P-7b may be indicative of an enhanced global C/O ratio. We compute Bond albedos of 0 ($<0.08$ at $1\sigma$) and $0.38\pm 0.06$ for WASP-19b and HAT-P-7b, respectively. In the context of other planets with thermal phase curve measurements, we show that WASP-19b and HAT-P-7b fit the general trend of decreasing day-night heat recirculation with increasing irradiation.Comment: 22 pages, 29 figures, accepted by Ap

Spitzer Secondary Eclipse Observations of Five Cool Gas Giant Planets and Empirical Trends in Cool Planet Emission Spectra

In this work we present Spitzer 3.6 and 4.5 micron secondary eclipse observations of five new cool (<1200 K) transiting gas giant planets: HAT-P-19b, WASP-6b, WASP-10b, WASP-39b, and WASP-67b. We compare our measured eclipse depths to the predictions of a suite of atmosphere models and to eclipse depths for planets with previously published observations in order to constrain the temperature- and mass-dependent properties of gas giant planet atmospheres. We find that the dayside emission spectra of planets less massive than Jupiter require models with efficient circulation of energy to the night side and/or increased albedos, while those with masses greater than that of Jupiter are consistently best-matched by models with inefficient circulation and low albedos. At these relatively low temperatures we expect the atmospheric methane to CO ratio to vary as a function of metallicity, and we therefore use our observations of these planets to constrain their atmospheric metallicities. We find that the most massive planets have dayside emission spectra that are best-matched by solar metallicity atmosphere models, but we are not able to place strong constraints on metallicities of the smaller planets in our sample. Interestingly, we find that the ratio of the 3.6 and 4.5 micron brightness temperatures for these cool transiting planets is independent of planet temperature, and instead exhibits a tentative correlation with planet mass. If this trend can be confirmed, it would suggest that the shape of these planets' emission spectra depends primarily on their masses, consistent with the hypothesis that lower-mass planets are more likely to have metal-rich atmospheres.Comment: 16 pages, 14 figures, accepted for publication in Ap

Effects of fuel content and density on the smoldering characteristics of cellulose and hemicellulose

Smoldering combustion in wildland fires poses hazards for both ecosystems and humans by destroying biomass, transitioning to flaming combustion, and releasing significant quantities of pollution. Understanding the parameters that control smoldering is necessary to help predict and potentially mitigate these hazards. A challenge in identifying these parameters is the wide variety of biomasses which occur in nature. The objective of this study is to identify the effects of density and fuel concentration on the smoldering characteristics of cellulose and hemicellulose mixtures. These fuels were considered because they are some of the major organic constituents within biomass. To this end, downward smoldering propagation velocities were measured for 50%, 75%, and 100% cellulose content at densities varying from 170 to 400 kg/m(3). The horizontal smoldering propagation velocities and temperature distributions were also determined for loosely packed samples ranging from 100% to 0% cellulose (with residual hemicellulose). Additionally, horizontal smoldering propagation velocities were determined for systematically varied ratios of cellulose (50-100%) and densities (200-400 kg/m(3)). The fuel was burned in an insulated reactor box. An infrared camera measured the horizontal propagation velocity, and thermocouples measured the downward propagation. A one-dimensional reactive porous media model with reduced chemistry was used to identify key processes causing the observed sensitivities. At constant packing density, the propagation velocity increased as cellulose content decreased because of decreased heat release with increased cellulose content and the earlier onset of hemicellulose pyrolysis. The propagation velocity decreased with respect to packing density when the fuel content was constant because of reduced oxygen diffusion. The propagation velocity increased with cellulose content when the fuel was loosely packed because of the decreasing density. (C) 2018 The Combustion Institute. Published by Elsevier Inc. All rights reserved

Flexible attention allocation to visual and auditory working memory tasks: manipulating reward induces a trade-off

Prominent roles for general attention resources are posited in many models of working memory, but the manner in which these can be allocated differs between models or is not sufficiently specified. We varied the payoffs for correct responses in two temporally-overlapping recognition tasks, a visual array comparison task and a tone sequence comparison task. In the critical conditions, an increase in reward for one task corresponded to a decrease in reward for the concurrent task, but memory load remained constant. Our results show patterns of interference consistent with a trade-off between the tasks, suggesting that a shared resource can be flexibly divided, rather than only fully allotted to either of the tasks. Our findings support a role for a domain-general resource in models of working memory, and furthermore suggest that this resource is flexibly divisible

Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1)

Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a cochaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test for potential ASD-like phenotypes. We found that increased STIP1 regulates the abundance of Hsp70 and Hsp90, whereas reduced STIP1 does not affect Hsp70, Hsp90 or the prion protein. Interestingly, BAC transgenic mice presenting fivefold more STIP1 show no major phenotype when examined in a series of behavioral tasks, including locomotor activity, elevated plus maze, Morris water maze and five-choice serial reaction time task (5-CSRTT). In contrast, mice with reduced STIP1 levels are hyperactive and have attentional deficits on the 5-CSRTT, but exhibit normal performance for the other tasks. We conclude that reduced STIP1 levels can contribute to phenotypes related to ASD. However, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes