Aberrantly Expressed Hsa_circ_0060762 and CSE1L as Potential Peripheral Blood Biomarkers for ALS

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive adult-onset neurodegenerative disease that is often diagnosed with a delay due to initial non-specific symptoms. Therefore, reliable and easy-to-obtain biomarkers are an absolute necessity for earlier and more accurate diagnostics. Circular RNAs (circRNAs) have already been proposed as potential biomarkers for several neurodegenerative diseases. In this study, we further investigated the usefulness of circRNAs as potential biomarkers for ALS. We first performed a microarray analysis of circRNAs on peripheral blood mononuclear cells of a subset of ALS patients and controls. Among the differently expressed circRNA by microarray analysis, we selected only the ones with a host gene that harbors the highest level of conservation and genetic constraints. This selection was based on the hypothesis that genes under selective pressure and genetic constraints could have a major role in determining a trait or disease. Then we performed a linear regression between ALS cases and controls using each circRNA as a predictor variable. With a False Discovery Rate (FDR) threshold of 0.1, only six circRNAs passed the filtering and only one of them remained statistically significant after Bonferroni correction: hsa_circ_0060762 and its host gene CSE1L. Finally, we observed a significant difference in expression levels between larger sets of patients and healthy controls for both hsa_circ_0060762 and CSE1L. CSE1L is a member of the importin fi family and mediates inhibition of TDP-43 aggregation; the central pathogenicity in ALS and hsa_circ_0060762 has binding sites for several miRNAs that have been already proposed as biomarkers for ALS. In addition, receiver operating characteristics curve analysis showed diagnostic potential for CSE1L and hsa_circ_0060762. Hsa_circ_0060762 and CSE1L thus represent novel potential peripheral blood biomarkers and therapeutic targets for ALS

Active rejection-enhancement of spectrally adaptive liquid crystal geometric phase vortex coronagraphs

Geometric phase optical elements made of space-variant anisotropic media customarily find their optimal operating conditions when the half-wave retardance condition is fulfilled, which allows imparting polarization-dependent changes to an incident wavefront. In practice, intrinsic limitations of man-made manufacturing process or the finite spectrum of the light source lead to a deviation from the ideal behavior. This implies the implementation of strategies to compensate for the associated efficiency losses. Here we report on how the intrinsic tunable features of self-engineered liquid crystal topological defects can be used to enhance the rejection capabilities of spectrally adaptive vector vortex coronagraphs. We also discuss the extent of which current models enable to design efficient devices

Defect structures in nematic liquid crystals around charged particles

We numerically study the orientation deformations in nematic liquid crystals around charged particles. We set up a Ginzburg-Landau theory with inhomogeneous electric field. If the dielectric anisotropy varepsilon_1 is positive, Saturn ring defects are formed around the particles. For varepsilon_1<0, novel "ansa" defects appear, which are disclination lines with their ends on the particle surface. We find unique defect structures around two charged particles. To lower the free energy, oppositely charged particle pairs tend to be aligned in the parallel direction for varepsilon_1>0 and in the perpendicular plane for varepsilon_1<0 with respect to the background director . For identically charged pairs the preferred directions for varepsilon_1>0 and varepsilon_1<0 are exchanged. We also examie competition between the charge-induced anchoring and the short-range anchoring. If the short-range anchoring is sufficiently strong, it can be effective in the vicinity of the surface, while the director orientation is governed by the long-range electrostatic interaction far from the surface.Comment: 10 papes, 12 figures, to appear in European Physical Journal

Large Colloids in Cholesteric Liquid Crystals

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Self-assembly of colloid-cholesteric composites provides a possible route to switchable optical materials

Colloidal particles dispersed in liquid crystals can form new materials with tunable elastic and electro-optic properties. In a periodic `blue phase' host, particles should template into colloidal crystals with potential uses in photonics, metamaterials, and transformational optics. Here we show by computer simulation that colloid/cholesteric mixtures can give rise to regular crystals, glasses, percolating gels, isolated clusters, twisted rings and undulating colloidal ropes. This structure can be tuned via particle concentration, and by varying the surface interactions of the cholesteric host with both the particles and confining walls. Many of these new materials are metastable: two or more structures can arise under identical thermodynamic conditions. The observed structure depends not only on the formulation protocol, but also on the history of an applied electric field. This new class of soft materials should thus be relevant to design of switchable, multistable devices for optical technologies such as smart glass and e-paper.Comment: Manuscript with 3 figures plus supporting text and figure

Improving long term driving comfort by taking breaks - how break activity affects effectiveness

During long duration journeys, drivers are encouraged to take regular breaks. The benefits of breaks have been documented for safety; breaks may also be beneficial for comfort. The activity undertaken during a break may influence its effectiveness. Volunteers completed 3 journeys on a driving simulator. Each 130 min journey included a 10 min break after the first hour. During the break volunteers either stayed seated, left the simulator and sat in an adjacent room, or took a walk on a treadmill. The results show a reduction in driver discomfort during the break for all 3 conditions, but the effectiveness of the break was dependent on activity undertaken. Remaining seated in the vehicle provided some improvement in comfort, but more was experienced after leaving the simulator and sitting in an adjacent room. The most effective break occurred when the driver walked for 10 min on a treadmill. The benefits from taking a break continued until the end of the study (after a further hour of driving), such that comfort remained the best after taking a walk and worst for those who remained seated. It is concluded that taking a break and taking a walk is an effective method for relieving driving discomfort

Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial

The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m2) in the "3 plus 3" dose-escalation part. During expansion, they received 60 mg/m2 of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m2 administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.0% (95%CI, 16.3-67.7) with a median duration of response of 6.9 months (95%CI, 4.8-9.1). Clinical benefit rate was 66.7% (95%CI, 38.4-88.2) and median progression-free survival was 7.2 months (95%CI, 4.5-9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients

Numerical simulations of the flow and aerosol dispersion in a violent expiratory event: Outcomes of the "2022 International Computational Fluid Dynamics Challenge on violent expiratory events"

This paper presents and discusses the results of the "2022 International Computational Fluid Dynamics Challenge on violent expiratory events"aimed at assessing the ability of different computational codes and turbulence models to reproduce the flow generated by a rapid prototypical exhalation and the dispersion of the aerosol cloud it produces. Given a common flow configuration, a total of 7 research teams from different countries have performed a total of 11 numerical simulations of the flow dispersion by solving the Unsteady Reynolds Averaged Navier-Stokes (URANS) or using the Large-Eddy Simulations (LES) or hybrid (URANS-LES) techniques. The results of each team have been compared with each other and assessed against a Direct Numerical Simulation (DNS) of the exact same flow. The DNS results are used as reference solution to determine the deviation of each modeling approach. The dispersion of both evaporative and non-evaporative particle clouds has been considered in 12 simulations using URANS and LES. Most of the models predict reasonably well the shape and the horizontal and vertical ranges of the buoyant thermal cloud generated by the warm exhalation into an initially quiescent colder ambient. However, the vertical turbulent mixing is generally underpredicted, especially by the URANS-based simulations, independently of the specific turbulence model used (and only to a lesser extent by LES). In comparison to DNS, both approaches are found to overpredict the horizontal range covered by the small particle cloud that tends to remain afloat within the thermal cloud well after the flow injection has ceased

Laser-directed hierarchical assembly of liquid crystal defects and control of optical phase singularities

Topological defect lines are ubiquitous and important in a wide variety of fascinating phenomena and theories in many fields ranging from materials science to early-universe cosmology, and to engineering of laser beams. However, they are typically hard to control in a reliable manner. Here we describe facile erasable “optical drawing” of self-assembled defect clusters in liquid crystals. These quadrupolar defect clusters, stabilized by the medium's chirality and the tendency to form twisted configurations, are shaped into arbitrary two-dimensional patterns, including reconfigurable phase gratings capable of generating and controlling optical phase singularities in laser beams. Our findings bridge the studies of defects in condensed matter physics and optics and may enable applications in data storage, singular optics, displays, electro-optic devices, diffraction gratings, as well as in both optically- and electrically-addressed pixel-free spatial light modulators