Near-Field Spectroscopy of Individual Asymmetric Split-Ring Terahertz Resonators

Metamaterial resonators have become an efficient and versatile platform in the terahertz frequency range, finding applications in integrated optical devices, such as active modulators and detectors, and in fundamental research, e.g., ultrastrong light–matter investigations. Despite their growing use, characterization of modes supported by these subwavelength elements has proven to be challenging and it still relies on indirect observation of the collective far-field transmission/reflection properties of resonator arrays. Here, we present a broadband time-domain spectroscopic investigation of individual metamaterial resonators via a THz aperture scanning near-field microscope (a-SNOM). The time-domain a-SNOM allows the mapping and quantitative analysis of strongly confined modes supported by the resonators. In particular, a cross-polarized configuration presented here allows an investigation of weakly radiative modes. These results hold great potential to advance future metamaterial-based optoelectronic platforms for fundamental research in THz photonics.

Resolving the inner jet structure of 1924-292 with the EVENT HORIZON TELESCOPE

We present the first 1.3 mm (230 GHz) very long baseline interferometry model image of an AGN jet using closure phase techniques with a four-element array. The model image of the quasar 1924-292 was obtained with four telescopes at three observatories: the James Clerk Maxwell Telescope (JCMT) on Mauna Kea in Hawaii, the Arizona Radio Observatory's Submillimeter Telescope (SMT) in Arizona, and two telescopes of the Combined Array for Research in Millimeterwave Astronomy (CARMA) in California in April 2009. With the greatly improved resolution compared with previous observations and robust closure phase measurement, the inner jet structure of 1924-292 was spatially resolved. The inner jet extends to the northwest along a position angle of $-53^\circ$ at a distance of 0.38\,mas from the tentatively identified core, in agreement with the inner jet structure inferred from lower frequencies, and making a position angle difference of $\sim 80^{\circ}$ with respect to the cm-jet. The size of the compact core is 0.15\,pc with a brightness temperature of $1.2\times10^{11}$\,K. Compared with those measured at lower frequencies, the low brightness temperature may argue in favor of the decelerating jet model or particle-cascade models. The successful measurement of closure phase paves the way for imaging and time resolving Sgr A* and nearby AGN with the Event Horizon Telescope.Comment: 6 pages, 4 figures, accepted for publication in ApJ

Radial Velocity Studies of Close Binary Stars. XI

Radial-velocity measurements and sine-curve fits to the orbital radial velocity variations are presented for ten close binary systems: DU Boo, ET Boo, TX Cnc, V1073 Cyg, HL Dra, AK Her, VW LMi, V566 Oph, TV UMi and AG Vir. By this contribution, the DDO program has reached the point of 100 published radial velocity orbits. The radial velocities have been determined using an improved fitting technique which uses rotational profiles to approximate individual peaks in broadening functions. Three systems, ET Boo, VW LMi and TV UMi, were found to be quadruple while AG Vir appears to be a spectroscopic triple. ET Boo, a member of a close visual binary with $P_{vis} = 113$ years, was previously known to be a multiple system, but we show that the second component is actually a close, non-eclipsing binary. The new observations enabled us to determine the spectroscopic orbits of the companion, non-eclipsing pairs in ET Boo and VW LMi. The particularly interesting case is VW LMi, where the period of the mutual revolution of the two spectroscopic binaries is only 355 days. While most of the studied eclipsing pairs are contact binaries, ET Boo is composed of two double-lined detached binaries and HL Dra is single-lined detached or semi-detached system. Five systems of this group were observed spectroscopically before: TX Cnc, V1073 Cyg, AK Her (as a single-lined binary), V566 Oph, AG Vir, but our new data are of much higher quality than the previous studies.Comment: Accepted by AJ, August 2006, 10 figures, 3 table

Noroviruses Co-opt the Function of Host Proteins VAPA and VAPB for Replication via a Phenylalanine-Phenylalanine-Acidic-Tract-Motif Mimic in Nonstructural Viral Protein NS1/2.

The Norovirus genus contains important human pathogens, but the role of host pathways in norovirus replication is largely unknown. Murine noroviruses provide the opportunity to study norovirus replication in cell culture and in small animals. The human norovirus nonstructural protein NS1/2 interacts with the host protein VAMP-associated protein A (VAPA), but the significance of the NS1/2-VAPA interaction is unexplored. Here we report decreased murine norovirus replication in VAPA- and VAPB-deficient cells. We characterized the role of VAPA in detail. VAPA was required for the efficiency of a step(s) in the viral replication cycle after entry of viral RNA into the cytoplasm but before the synthesis of viral minus-sense RNA. The interaction of VAPA with viral NS1/2 proteins is conserved between murine and human noroviruses. Murine norovirus NS1/2 directly bound the major sperm protein (MSP) domain of VAPA through its NS1 domain. Mutations within NS1 that disrupted interaction with VAPA inhibited viral replication. Structural analysis revealed that the viral NS1 domain contains a mimic of the phenylalanine-phenylalanine-acidic-tract (FFAT) motif that enables host proteins to bind to the VAPA MSP domain. The NS1/2-FFAT mimic region interacted with the VAPA-MSP domain in a manner similar to that seen with bona fide host FFAT motifs. Amino acids in the FFAT mimic region of the NS1 domain that are important for viral replication are highly conserved across murine norovirus strains. Thus, VAPA interaction with a norovirus protein that functionally mimics host FFAT motifs is important for murine norovirus replication.IMPORTANCE Human noroviruses are a leading cause of gastroenteritis worldwide, but host factors involved in norovirus replication are incompletely understood. Murine noroviruses have been studied to define mechanisms of norovirus replication. Here we defined the importance of the interaction between the hitherto poorly studied NS1/2 norovirus protein and the VAPA host protein. The NS1/2-VAPA interaction is conserved between murine and human noroviruses and was important for early steps in murine norovirus replication. Using structure-function analysis, we found that NS1/2 contains a short sequence that molecularly mimics the FFAT motif that is found in multiple host proteins that bind VAPA. This represents to our knowledge the first example of functionally important mimicry of a host FFAT motif by a microbial protein

Near-Field Spectroscopy of Individual Asymmetric Split-Ring Terahertz Resonators

Metamaterial resonators have become an efficient and versatile platform in the terahertz frequency range, finding applications in integrated optical devices, such as active modulators and detectors, and in fundamental research, e.g., ultrastrong light–matter investigations. Despite their growing use, characterization of modes supported by these subwavelength elements has proven to be challenging and it still relies on indirect observation of the collective far-field transmission/reflection properties of resonator arrays. Here, we present a broadband time-domain spectroscopic investigation of individual metamaterial resonators via a THz aperture scanning near-field microscope (a-SNOM). The time-domain a-SNOM allows the mapping and quantitative analysis of strongly confined modes supported by the resonators. In particular, a cross-polarized configuration presented here allows an investigation of weakly radiative modes. These results hold great potential to advance future metamaterial-based optoelectronic platforms for fundamental research in THz photonics

Hydroxychloroquine prescription trends and predictors for excess dosing per recent ophthalmology guidelines

Background Hydroxychloroquine (HCQ) retinopathy may be more common than previously recognized; recent ophthalmology guidelines have revised recommendations from ideal body weight (IBW)-based dosing to actual body weight (ABW)-based dosing. However, contemporary HCQ prescribing trends in the UK remain unknown. Methods We examined a UK general population database to investigate HCQ dosing between 2007 and 2016. We studied trends of excess HCQ dosing per ophthalmology guidelines (defined by exceeding 6.5 mg/kg of IBW and 5.0 mg/kg of ABW) and determined their independent predictors using multivariable logistic regression analyses. Results Among 20,933 new HCQ users (78% female), the proportions of initial HCQ excess dosing declined from 40% to 36% using IBW and 38% to 30% using ABW, between 2007 and 2016. Among these, 47% of women were excess-dosed (multivariable OR 12.52; 95% CI 10.99–14.26) using IBW and 38% (multivariable OR 1.98; 95% CI,1.81–2.15) using ABW. Applying IBW, 37% of normal and 44% of obese patients were excess-dosed; however, applying ABW, 53% of normal and 10% of obese patients were excess-dosed (multivariable ORs = 1.61 and 0.1 (reference = normal); both p < 0.01). Long-term HCQ users showed similar excess dosing. Conclusion A substantial proportion of HCQ users in the UK, particularly women, may have excess HCQ dosing per the previous or recent weight-based guidelines despite a modest decline in recent years. Over half of normal-BMI individuals were excess-dosed per the latest guidelines. This implies the potential need to reduce dosing for many patients but also calls for further research to establish unifying evidence-based safe and effective dosing strategies

Detection of intrinsic source structure at ~3 Schwarzschild radii with Millimeter-VLBI observations of SAGITTARIUS A*

We report results from very long baseline interferometric (VLBI) observations of the supermassive black hole in the Galactic center, Sgr A*, at 1.3 mm (230 GHz). The observations were performed in 2013 March using six VLBI stations in Hawaii, California, Arizona, and Chile. Compared to earlier observations, the addition of the APEX telescope in Chile almost doubles the longest baseline length in the array, provides additional {\it uv} coverage in the N-S direction, and leads to a spatial resolution of $\sim$30 $\mu$as ($\sim$3 Schwarzschild radii) for Sgr A*. The source is detected even at the longest baselines with visibility amplitudes of $\sim$4-13% of the total flux density. We argue that such flux densities cannot result from interstellar refractive scattering alone, but indicate the presence of compact intrinsic source structure on scales of $\sim$3 Schwarzschild radii. The measured nonzero closure phases rule out point-symmetric emission. We discuss our results in the context of simple geometric models that capture the basic characteristics and brightness distributions of disk- and jet-dominated models and show that both can reproduce the observed data. Common to these models are the brightness asymmetry, the orientation, and characteristic sizes, which are comparable to the expected size of the black hole shadow. Future 1.3 mm VLBI observations with an expanded array and better sensitivity will allow a more detailed imaging of the horizon-scale structure and bear the potential for a deep insight into the physical processes at the black hole boundary.Comment: 11 pages, 5 figures, accepted to Ap

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation