Search

Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date. In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions). Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI-treated patients in groups 2 and 3 but not in group 1. Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations. • The EGFR-TKI efficacy of in uncommon EGFR mutations generally considered TKI sensitive was validated. • Complex EGFR mutations containing exon19del or L858R were EGFR-TKI sensitive, independent of the combination partner. • Very rare single and complex mutations, comprising 40% of atypical mutations, show a high heterogeneity of TKI sensitivity. • TP53 co-mutations may confer a detrimental outcome in TKI-treated patients with very rare EGFR mutations and exon20ins. • We propose a novel nNGM classification for atypical EGFR mutations. [ABSTRACT FROM AUTHOR]

Tumor molecular analyses in endometrial cancer (EC) includes 4 distinct subtypes: (1) POLE -mutated, (2) mismatch repair protein (MMR) deficient, (3) p53 mutant, and (4) no specific molecular profile. Recently, a sub-analysis of PORTEC-3 demonstrated notable differences in treatment response between molecular classification (MC) groups. Cost of testing is one barrier to widespread adoption of MC. Therefore, we sought to determine the cost-effectiveness of MC in patients with stage I and II high-risk EC. A Markov decision model was developed to compare tumor molecular classification (TMC) vs. no testing (NT). A healthcare payor's perspective and 5-year time horizon were used. Base case data were abstracted from PORTEC-3 and the molecular sub-analysis. Cost and utility data were derived from public databases, peer-reviewed literature, and expert input. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Sensitivity analyses were performed to test model robustness. When compared to NT, TMC was cost effective with an ICER of $25,578 per QALY gained; incremental cost was $1780 and incremental effectiveness was 0.070 QALYs. In one-way sensitivity analyses, results were most sensitive to the cost of POLE testing, but TMC remained cost-effective over all parameter ranges. TMC in early-stage high-risk EC is cost-effective, and the model results were robust over a range of parameters. Given that MC can be used to guide adjuvant treatment decisions, these findings support adoption of TMC into routine practice. • Tumor molecular testing is a rapidly emerging area of research in endometrial cancer and may guide adjuvant treatment. • A Markov decision model was developed to compare tumor molecular classification versus no molecular testing. • Compared to no testing, tumor molecular classification is a highly cost-effective strategy. [ABSTRACT FROM AUTHOR]

Context. The emergence of optical interferometers with three and more telescopes allows image reconstruction of astronomical objects at the milliarcsecond scale. However, some objects contain components with very different spectral energy distributions (SED; i.e. different temperatures), which produces strong chromatic effects on the interferograms that have to be managed with care by image reconstruction algorithms. For example, the gray approximation for the image reconstruction process results in a degraded image if the total (u; v)-coverage given by the spectral supersynthesis is used. Aims. The relative flux contribution of the central object and an extended structure changes with wavelength for different temperatures. For young stellar objects, the known characteristics of the central object (i.e., stellar SED), or even the fit of the spectral index and the relative flux ratio, can be used to model the central star while reconstructing the image of the extended structure separately. Methods. We present a new method, called SPARCO (semi-parametric algorithm for the image reconstruction of chromatic objects), which describes the spectral characteristics of both the central object and the extended structure to consider them properly when reconstructing the image of the surrounding environment. We adapted two image-reconstruction codes (Macim, Squeeze, and MiRA) to implement this new prescription. Results. SPARCO is applied using Macim, Squeeze, and MiRA on a young stellar object model and also on literature data on HR 5999 in the near-infrared with the VLTI. We obtain smoother images of the modeled circumstellar emission and improve the X2 by a factor 9. Conclusions. This method paves the way to improved aperture-synthesis imaging of several young stellar objects with existing datasets. More generally, the approach can be used on astrophysical sources with similar features, such as active galactic nuclei, planetary nebulae, and asymptotic giant branch stars. [ABSTRACT FROM AUTHOR]

Aims: We aim to refine the dynamical masses of the individual component of the low-mass pre-main sequence binary Haro 1-14C. Methods: We combine the data of the preliminary orbit presented previously with new interferometric observations obtained with the four 8 m telescopes of the Very Large Telescope Interferometer. Results: The derived masses are Ma = 0.905 ± 0.043 Mʘ and Mb = 0.308 ± 0.011 Mʘ for the primary and secondary components, respectively. This is about five times better than the uncertainties of the preliminary orbit. Moreover, the possibility of larger masses is now securely discarded. The new dynamical distance, d = 96 ± 9 pc, is smaller than the distance to the Ophiuchus core with a significance of 2.6s. Fitting the spectral energy distribution yields apparent diameters of fa = 0.13 ± 0.01 mas and fb = 0.10 ± 0.01 mas (corresponding to Ra = 1.50 Rʘ and Rb = 1.13 ʘ) and a visual extinction of Av 1.75. Although the revised orbit has a nearly edge-on geometry, the system is unlikely to be a long-period eclipsing binary. Conclusions. The secondary in Haro 1-14C is one of the few low-mass, pre-main sequence stars with an accurately determined dynamical mass and distance. [ABSTRACT FROM AUTHOR]

In the course of our VLTI young stellar object PIONIER imaging program, we have identified a strong visibility chromatic dependency that appeared in certain sources. This effect, rising value of visibilities with decreasing wavelengths over one base, is also present in previous published and archival AMBER data. For Herbig AeBe stars, the H band is generally located at the transition between the star and the disk predominance in flux for Herbig AeBe stars. We believe that this phenomenon is responsible for the visibility rise effect. We present a method to correct the visibilities from this effect in order to allow "gray" image reconstruction software, like Mira, to be used. In parallel we probe the interest of carrying an image reconstruction in each spectral channel and then combine them to obtain the final broadband one. As an illustration we apply these imaging methods to MWC158, a (possibly Herbig) B[e] star intensively observed with PIONIER. Finally, we compare our result with a parametric model fitted onto the data. [ABSTRACT FROM AUTHOR]

Mechanical properties of metal films on polymer substrates are normally studied in terms of the fracture and adhesion of the film, while the properties of the polymer substrate and testing conditions are overlooked. Substrate orientation and thickness, as well as strain rate and temperature effects, are examined using Cr films deposited onto polyethylene terephthalate substrates. A faster strain rate affects only the initial fracture strain of the Cr film and not the crack and buckle spacings in the high strain condition. The substrate orientation slightly changes the average crack spacing while the substrate thickness has little effect on the cracking and buckling behaviour. Straining experiments at high temperature increased the average crack spacing and led to a change in buckling mode. The lack of sizeable changes in the mechanical behaviour over the large range of testing procedures leads to a resilient material system for flexible applications. [ABSTRACT FROM AUTHOR]

Context. Optical interferometers are subject to many atmospheric and instrumental artifacts that contribute to the degradation of their instrumental contrast, hence their performances. The differential birefringence is, among these effects, one of the trickiest to control, in particular for instrument using fibers, where it can be far larger than the one arising in the optical mirror trains. Several solutions have been tested in the past, ranging from polarization splitting to fiber tweaking. We adopt a new solution for the PIONIER instrument, a four-telescope (4T) combiner at the Very Large Telescope Interferometer (VLTI). Aims. We present a method to cancel the instrumental birefringence in an optical interferometer, allowing the joint detection of the fringe patterns of both polarizations, and substantial gains to be made in both signal-to-noise ratio and readout speed. Methods. A thin (2 mm) plate of birefringent material (LiNbO3) is inserted in each of the four beams. The incidence angle of each plate is adjustable. This allows us to introduce a controlled amount of birefringence in each beam and to cancel the instrumental differential birefringence. We present our derivation of the induced birefringence versus incidence angle and discuss the design choices. Results. Our proposed solution is implemented in the Pionier instrument. Before correction, the instrumental birefringence was of order 5 μm (path length). The adjustment takes about one hour, results in a birefringence of less than 0.1 μm, and is stable for at least the duration of an observing run (several days). Conclusions. We demonstrate on an operational near-infrared interferometer a novel, simple, low-cost, and effective technique to control the differential birefringence. The predictability and stability of the correction make this technique ideal for an automated correction in the VLTI second generation instruments. [ABSTRACT FROM AUTHOR]

Summary Background: Light transmission aggregometry (LTA) is considered the gold standard for investigating platelet activity ex vivo. However, LTA protocols are not standardized, and differences in LTA procedure are a potential source of variance in results. Centrifugation speed is an essential component of platelet preparation in LTA, has yet to be standardized, and may affect platelet aggregation results. We sought to investigate the effect of relative centrifugal force (RCF) intensity on LTA results. Methods: Ten healthy controls had venous blood drawn and centrifuged at 150, 200, 300, and 500 g for 10 min. Cell counts in whole blood and platelet-rich plasma (PRP) were measured using a hematology analyzer. LTA was performed using 1.0 μ m adenosine diphosphate (ADP) and 0.4 μ m epinephrine as an agonist. Aggregation (%) was compared at 60, 120, 180, and 300 s and at maximum aggregation. Results: Centrifugation speed was associated with decreasing platelet count ( P < 0.001) and decreasing mean platelet volume ( P < 0.001) in PRP. Maximum aggregation decreased with increasing speeds for ADP 1.0 μ m (150 g- 89%, 200 g- 93%, 300 g- 71%, 500 g- 17%; P < 0.001). Similar findings were noted at 120 s (150 g- 69%, 200 g- 50%, 300 g- 35%, 500 g- 12%; P < 0.001), 180 s (150 g- 82%, 200 g- 74%, 300 g- 44%, 500 g- 13%; P < 0.001), and 300 s (150 g- 85%, 200 g- 88%, 300 g- 55%, 500 g- 14%; P < 0.001). Consistently, platelet aggregation in response to epinephrine 0.4 μ m decreased significantly with increasing centrifuge RCF at 60, 120, 180, 300 s and at maximum aggregation ( P < 0.05 for each comparison). Conclusion: Our data demonstrate the importance of centrifugation speed in the interpretation of LTA results, supporting the need for standardization of centrifugation RCF in LTA protocols. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the improvement in the overall survival and progression of donor inhibitory killer cell immunoglobulin-like receptors (KIRs) haplotype B patients after undergoing an allogeneic hematopoietic stem cell transplantation used for multiple myeloma.

A microscopic theory for the decay of a compound nucleus is presented which is formulated in the spirit of transport theories. Its basic physical assumption is the existence of two time scales, a rapid one concerning the creation of intrinsic excitations and a slow one controlling the change of the nuclear shape. This fact is used in the derivation of an equation of motion for the reduced density by applying the so-called Markov approximation. A canonical distribution of the system with regard to the intrinsic excitations at a given shape is assumed as an approximation and a temperature T(q, t) depending on the nuclear shapes and time t is defined so as to render the canonical distribution as realistic as possible. [ABSTRACT FROM AUTHOR]

Abstract: We formulate a microscopic theory of the decay of a compound nucleus through fission which generalizes earlier microscopic approaches of fission dynamics performed in the framework of the adiabatic hypothesis. It is based on the constrained Hartree–Fock–Bogoliubov procedure and the Generator Coordinate Method, and requires an effective nucleon–nucleon interaction as the only input quantity. The basic assumption is that the slow evolution of the nuclear shape must be treated explicitly, whereas the rapidly time-dependent intrinsic excitations can be treated by statistical approximations. More precisely, we introduce a “reference density” which represents the slow evolution of the nuclear shape by a reduced density matrix and the state of intrinsic excitations by a canonical distribution at each given shape of the nucleus. The shape of the nuclear density distribution is described by parameters (“generator coordinates”q), not by “superabundant” degrees of freedom introduced in addition to the complete set of nucleonic degrees of freedom. We first derive a rigorous equation of motion for the reference density and, subsequently, simplify this equation on the basis of the “Markov approximation”. The temperature T which appears in the canonical distribution is determined by the requirement that, at each time t, the reference density should correctly reproduce the mean excitation energy at given values of the shape parameters q. The resulting equation for the “local” temperature must be solved together with the equations of motion obtained for the reduced density matrix . [Copyright &y& Elsevier]

The exercise carbon dioxide equivalent slope predicts prognosis in coronary artery disease patients. However, no study examined whether the carbon dioxide equivalent slope in coronary artery disease patients is dependent on the type of exercise. Twenty-nine coronary artery disease patients performed maximal cardiopulmonary exercise tests on bike, treadmill and arm cycle, with assessment of oxygen uptake, carbon dioxide output, and expiratory volume. The carbon dioxide equivalent slope was calculated from rest till peak exercise. The carbon dioxide equivalent slope was significantly different between walking, cycling, and arm cranking exercises (P<0.05), i.e. the carbon dioxide equivalent slope was the lowest during walking and the highest during arm cranking. Bland-Altman plots revealed that the difference of the carbon dioxide equivalent slope between exercises was greater in the case of a higher averaged carbon dioxide equivalent slope and overall peak oxygen uptake. In conclusion, the carbon dioxide equivalent slope is significantly dependent on the type of exercise in coronary artery disease patients. Additionally, the averaged carbon dioxide equivalent slope and peak oxygen uptake affect the difference of the carbon dioxide equivalent slopes between exercises. [ABSTRACT FROM AUTHOR]

The exercise carbon dioxide equivalent slope predicts prognosis in coronary artery disease patients. However, no study examined whether the carbon dioxide equivalent slope in coronary artery disease patients is dependent on the type of exercise. Twenty-nine coronary artery disease patients performed maximal cardiopulmonary exercise tests on bike, treadmill and arm cycle, with assessment of oxygen uptake, carbon dioxide output, and expiratory volume. The carbon dioxide equivalent slope was calculated from rest till peak exercise. The carbon dioxide equivalent slope was significantly different between walking, cycling, and arm cranking exercises (P<0.05), i.e. the carbon dioxide equivalent slope was the lowest during walking and the highest during arm cranking. Bland-Altman plots revealed that the difference of the carbon dioxide equivalent slope between exercises was greater in the case of a higher averaged carbon dioxide equivalent slope and overall peak oxygen uptake. In conclusion, the carbon dioxide equivalent slope is significantly dependent on the type of exercise in coronary artery disease patients. Additionally, the averaged carbon dioxide equivalent slope and peak oxygen uptake affect the difference of the carbon dioxide equivalent slopes between exercises. [ABSTRACT FROM AUTHOR]

A dynamical approach to the neutron-induced fission of 255,257Fm isotopes based on the time-dependent generator-coordinate method is applied. As the generating functions the eigensolutions of the constrained Hartree-Fock-Bogoliubov method with the effective D1S Gogny force are used. The here presented collective-dynamics calculations in the two-dimensional collective space described by quadrupole and octupole moments allow to determine the fragment mass distributions of those two Fm isotopes. [ABSTRACT FROM AUTHOR]

Two-dimensional Hartree-Fock-Bogoliubov (HFB) calculations have been performed from spherical shapes to large deformations with constraints on axial quadrupole and octupole deformations in 238U, 256–260Fm and 226Th actinides. Scission configurations have then been identified in this subspace of collective coordinates and many nuclear properties of the nascent fragments have been derived, such as deformation, deformation energy or prompt neutron multiplicity. The HFB states have then served as basis states for time-dependent collective calculations based on the Time-Dependent Generator Coordinate Method and the Gaussian Overlap Approximation to derive fission fragment yields. [ABSTRACT FROM AUTHOR]

With a help of the selfconsistent Hartree-Fock-Bogoliubov (HFB) approach with the D1S effective Gogny interaction and the Generator Coordinate Method (GCM) we incorporate the transverse collective vibrations to the one-dimensional model of the fission-barrier penetrability based on the traditional WKB method. The average fission barrier corresponding to the least-energy path in the two-dimensional potential energy landscape as function of quadrupole and octupole degrees of freedom is modified by the influence of the transverse collective vibrations along the nuclear path to fission. The set of transverse vibrational states built in the fission valley corresponding to a successively increasing nuclear elongation produces the new energy barrier which is compared with the least-energy barrier. These collective states are given as the eigensolutions of the GCM purely vibrational Hamiltonian. In addition, the influence of the collective inertia on the fission properties is displayed, and it turns out to be the decisive condition for the possible transitions between different fission valleys. [ABSTRACT FROM AUTHOR]

We present the case of an HIV-infected patient who developed life-threatening rhabdomyolysis and Fanconi syndrome 11 years after initiation of TDF-based combination antiretroviral therapy (cART). Apart from our patient, the association of rhabdomyolysis and concomitant tubular nephropathy has been reported in three other patients in the literature [[5]]. The tubular nephropathy was diagnosed as Fanconi syndrome in two patients and acute tubular necrosis in the two other patients. [Extracted from the article]

In this paper, we study the application of the method of fundamental solutions to the computation of stress intensity factors in linear elastic fracture mechanics. The displacements are approximated by linear combinations of the fundamental solutions of the Cauchy–Navier equations of elasticity and the leading terms for the displacement near the crack tip. The applicability of two formulations of the method is demonstrated on two mode I crack problems, where it is shown that accurate approximations for the stress intensity factors can be obtained with relatively few degrees of freedom. [ABSTRACT FROM AUTHOR]

Most of this paper consists of the derivation of general beam-referenced stage-two spin-correlation functions for the analysis of top-antitop pair production at the Tevatron, at the Large Hadron Collider, and/or at an International Linear Collider. However, for the charged-lepton plus jets reaction $q \bar{q} \rightarrow t \bar{t} \rightarrow (W^ + b) (W^- \bar{b} ) \rightarrow (l^{ + } \nu b ) (W^- \bar{b} )$ , there is a simple three-angle spin-correlation function for the determination of the relative sign of or for the measurement of a possible non-trivial phase between the two dominant λ b=-1/2 helicity amplitudes for the t → W + b decay mode. For the CP-conjugate case, there is an analogous function and tests for $\bar{t} \rightarrow W^{-} \bar{b}$ decay. These results make use of W-boson longitudinal-transverse interference. [ABSTRACT FROM AUTHOR]

Low energy fission is described using a microscopic and time-dependent approach. Fission dynamics is derived from the evolution of a collective wave function in the restricted space generated by the quadrupole and octupole collective variables. Propagation is made by use of the Time Dependent Generator Coordinate Method with a basis set of Hartree Fock Bogoliubov states obtained from self-consistent calculations with the Gogny force. Theoretical fragment mass and kinetic energy distributions in actinide fission are presented. First calculations with selected initial states indicate that the main features of experimental mass distributions in 238U are reproduced. The peak-to-valley ratio appears to significantly depend on the parity of the initial state chosen. [Copyright &y& Elsevier]

In this work we demonstrate the robustness of a real-space approach for the treatment of infinite systems described with periodic boundary conditions that we have recently proposed (Tavernier et al in J Phys Chem Lett 17:7090, 2000). In our approach we extract a fragment, i.e., a supercell, out of the infinite system, and then modifying its topology into the that of a Clifford torus which is a flat, finite and border-less manifold. We then renormalize the distance between two points by defining it as the Euclidean distance in the embedding space of the Clifford torus. With our method we have been able to calculate the reference results available in the literature with a remarkable accuracy, and at a very low computational effort. In this work we show that our approach is robust with respect to the shape of the supercell. In particular, we show that the Madelung constants converge to the same values but that the convergence properties are different. Our approach scales linearly with the number of atoms. The calculation of Madelung constants only takes a few seconds on a laptop computer for a relative precision of about 10 - 6 . [ABSTRACT FROM AUTHOR]

An analysis of singular solutions at corners consisting of several different homogeneous wedges is presented for anisotropic potential theory in plane. The concept of transfer matrix is applied for a singularity analysis first of single wedge problems and then of multi-material corner problems. Explicit forms of eigenequations for evaluation of singularity exponent in the case of multi-material corners are derived both for all combinations of homogeneous Neumann and Dirichlet boundary conditions at faces of open corners and for multi-material planes with singular interior points. Perfect transmission conditions at wedge interfaces are considered in both cases. It is proved that singularity exponents are real for open anisotropic multi-material corners, and a sufficient condition for the singularity exponents to be real for anisotropic multi-material planes is deduced. A case of a complex singularity exponent for an anisotropic multi-material plane is reported, apparently for the first time in potential theory. Simple expressions of eigenequations are presented first for open bi-material corners and bi-material planes and second for a crack terminating at a bi-material interface, as examples of application of the theory developed here. Analytical solutions of these eigenequations are presented for interface cracks with any combination of homogeneous boundary conditions along the interface crack faces, and also for a special case of a crack perpendicular to a bi-material interface. A numerical study of variation of the singularity exponent as a function of inclination of a crack terminating at a bi-material interface is presented. [Copyright &y& Elsevier]

Changes in protein glycosylation of tumour cells, as detected by lectin histochemistry, have been associated with metastasis formation in several human malignancies. This study analysed the association between lectin binding and metastasis in cutaneous malignant melanoma. In a 10-year retrospective study, sections of 100 primary cutaneous malignant melanomas were histochemically stained for the following 5 lectins: HPA, SNA-I, MAA, WGA and PHA-L, differing in their carbohydrate specificity. Since differences in the results of HPA binding depending on methodology have been reported, an indirect and a biotinylated method were employed for HPA. Kaplan-Meier analysis of time to first metastasis revealed a positive correlation between HPA binding and metastasis for both methods, with the biotinylated HPA method (P < 0.0001) being superior to the 'indirect' method (P = 0.0006). Cox regression analysis demonstrated that even after adjustment for stage, HPA positivity is an independent predictor for metastasis. The results of the present study indicate that N-acetyl-galactosamine/-glucosamine residues, recognized by HPA, are linked to metastasis in malignant melanoma. In contrast, β1-6 branched oligosaccharides or sialic acid residues, both of which were correlated with metastasis in other malignancies, are of no functional importance for metastasis formation in malignant melanoma. Thus, HPA proved to be a useful and independent prognostic marker for the metastatic phenotype of melanoma. [ABSTRACT FROM AUTHOR]

The clinical features of human immunodeficiency virus (HIV) dementia exhibit the hallmarks of a subcortical dementia. These features include psychomotor slowing, apathy, bradykinesia and altered posture and gait similar to those observed in advanced Parkinson's disease. The dementia has the hallmarks attributed to subcortical dementia. The exquisite sensitivity of many of these patients to dopamine receptor blockade suggested a profound and, perhaps, selective abnormality of striatal dopaminergic systems. Additional investigations, electrophysiological, pathological, virological, metabolic and radiological studies, indicate that the basal ganglia are a major target of HIV infection. In this review, we describe the evidence for involvement of basal ganglia and, in particular, the dopaminergic systems, in HIV dementia. We also suggest novel therapeutic strategies that may be beneficial in the treatment of this disorder. [ABSTRACT FROM AUTHOR]

We report experimental tests of the present models of the peak effect in weakly disordered type-II superconductors. Our results favour the scenario in which the peak effect arises from a crossover between the Larkin pinning length and a rapidly falling elastic length in a vortex phase populated with thermally excited topological defects. A thickness dependence study of the onset of the peak effect at varying driving currents suggests that both screw and edge dislocations are involved in the vortex lattice disordering. The driven dynamics in threedimensional samples are drastically different from those in two-dimensional samples. We suggest that this may be a consequence of the absence of a Peierls potential for screw dislocations in a three-dimensional vortex line lattice. [ABSTRACT FROM AUTHOR]

The spin of the supermassive black hole that resides at the Galactic Center can, in principle, be measured by accurate measurements of the orbits of stars that are much closer to Sgr A* than S2, the orbit of which recently provided the measurement of the gravitational redshift and the Schwarzschild precession. The GRAVITY near-infrared interferometric instrument combining the four 8m telescopes of the VLT provides a spatial resolution of 2–4 mas, breaking the confusion barrier for adaptive-optics-assisted imaging with a single 8–10m telescope. We used GRAVITY to observe Sgr A* over a period of six months in 2019 and employed interferometric reconstruction methods developed in radio astronomy to search for faint objects near Sgr A*. This revealed a slowly moving star of magnitude 18.9 in the K-band within 30 mas of Sgr A*. The position and proper motion of the star are consistent with the previously known star S62, which is at a substantially greater physical distance, but in projection passes close to Sgr A*. Observations in August and September 2019 detected S29 easily, with K-magnitude of 16.6, at approximately 130 mas from Sgr A*. The planned upgrades of GRAVITY, and further improvements in the calibration, offer greater chances of finding stars fainter than K-magnitude of 19. [ABSTRACT FROM AUTHOR]

The combination of the high intensity proton beam facilities and massive detectors for precision measurements of neutrino oscillation parameters including the charge-parity violating (CPV) phase will open the door to help make beyond the standard model (BSM) physics reachable even in low energy regimes in the accelerator-based experiments. Large-mass detectors with highly precise tracking and energy measurements, excellent timing resolution, and low energy thresholds will enable the searches for BSM phenomena from cosmogenic origin, as well. Therefore, it is also conceivable that BSM topics in the next-generation neutrino experiments could be the dominant physics topics in the foreseeable future, as the precision of the neutrino oscillation parameter and CPV measurements continue to improve.This paper provides a review of the current landscape of BSM theory in neutrino experiments in two selected areas of the BSM topics—dark matter and neutrino related BSM—and summarizes the current results from existing neutrino experiments to set benchmarks for both theory and experiment. This paper then provides a review of upcoming neutrino experiments throughout the next 10 to 15 year time scale and their capabilities to set the foundation for potential reach in BSM physics in the two aforementioned themes. An important outcome of this paper is to ensure theoretical and simulation tools exist to carry out studies of these new areas of physics, from the first day of the experiments, such as Deep Underground Neutrino Experiment in the U.S. and Hyper-Kamiokande Experiment in Japan. [ABSTRACT FROM AUTHOR]

Context. Young stars interact with their accretion disk through their strong magnetosphere. Aims. We aim to investigate the magnetospheric accretion/ejection process in the young stellar system DoAr 44 (V2062 Oph). Methods. We monitored the system over several rotational cycles, combining high-resolution spectropolarimetry at both optical and near-IR wavelengths with long-baseline near-IR inteferometry and multicolor photometry. Results. We derive a rotational period of 2.96 d from the system's light curve, which is dominated by stellar spots. We fully characterize the central star's properties from the high signal-to-noise, high-resolution optical spectra we obtained during the campaign. DoAr 44 is a young 1.2 M⊙ star, moderately accreting from its disk (Ṁacc = 6.5 10−9M⊙ yr−1), and seen at a low inclination (i ≃ 30°). Several optical and near-IR line profiles probing the accretion funnel flows (Hα, Hβ, HeI 1083 nm, Paβ) and the accretion shock (HeI 587.6 nm) are modulated at the stellar rotation period. The most variable line profile is HeI 1083 nm, which exhibits modulated redshifted wings that are a signature of accretion funnel flows, as well as deep blueshifted absorptions indicative of transient outflows. The Zeeman-Doppler analysis suggests the star hosts a mainly dipolar magnetic field, inclined by about 20° onto the spin axis, with an intensity reaching about 800 G at the photosphere, and up to 2 ± 0.8 kG close to the accretion shock. The magnetic field appears strong enough to disrupt the inner disk close to the corotation radius, at a distance of about 4.6 R⋆ (0.043 au), which is consistent with the 5 R⋆ (0.047 au) upper limit we derived for the size of the magnetosphere in our Paper I from long baseline interferometry. Conclusions. DoAr 44 is a pre-transitional disk system, exhibiting a 25–30 au gap in its circumstellar disk, with the inner and outer disks being misaligned. On a scale of 0.1 au or less, our results indicate that the system is steadily accreting from its inner disk through its tilted dipolar magnetosphere. We conclude that in spite of a highly structured disk on the large scale, perhaps the signature of ongoing planetary formation, the magnetospheric accretion process proceeds unimpeded at the star-disk interaction level. [ABSTRACT FROM AUTHOR]

We study the time-variable linear polarisation of Sgr A* during a bright near-infrared flare observed with the GRAVITY instrument on July 28, 2018. Motivated by the time evolution of both the observed astrometric and polarimetric signatures, we interpret the data in terms of the polarised emission of a compact region ("hotspot") orbiting a black hole in a fixed, background magnetic field geometry. We calculated a grid of general relativistic ray-tracing models, created mock observations by simulating the instrumental response, and compared predicted polarimetric quantities directly to the measurements. We take into account an improved instrument calibration that now includes the instrument's response as a function of time, and we explore a variety of idealised magnetic field configurations. We find that the linear polarisation angle rotates during the flare, which is consistent with previous results. The hotspot model can explain the observed evolution of the linear polarisation. In order to match the astrometric period of this flare, the near horizon magnetic field is required to have a significant poloidal component, which is associated with strong and dynamically important fields. The observed linear polarisation fraction of ≃30% is smaller than the one predicted by our model (≃50%). The emission is likely beam depolarised, indicating that the flaring emission region resolves the magnetic field structure close to the black hole. [ABSTRACT FROM AUTHOR]

Context. Methods used to detect giant exoplanets can be broadly divided into two categories: indirect and direct. Indirect methods are more sensitive to planets with a small orbital period, whereas direct detection is more sensitive to planets orbiting at a large distance from their host star. This dichotomy makes it difficult to combine the two techniques on a single target at once. Aims. Simultaneous measurements made by direct and indirect techniques offer the possibility of determining the mass and luminosity of planets and a method of testing formation models. Here, we aim to show how long-baseline interferometric observations guided by radial-velocity can be used in such a way. Methods. We observed the recently-discovered giant planet β Pictoris c with GRAVITY, mounted on the Very Large Telescope Interferometer. Results. This study constitutes the first direct confirmation of a planet discovered through radial velocity. We find that the planet has a temperature of T = 1250 ± 50 K and a dynamical mass of M = 8.2 ± 0.8 MJup. At 18.5 ± 2.5 Myr, this puts β Pic c close to a 'hot start' track, which is usually associated with formation via disk instability. Conversely, the planet orbits at a distance of 2.7 au, which is too close for disk instability to occur. The low apparent magnitude (MK = 14.3 ± 0.1) favours a core accretion scenario. Conclusions. We suggest that this apparent contradiction is a sign of hot core accretion, for example, due to the mass of the planetary core or the existence of a high-temperature accretion shock during formation. [ABSTRACT FROM AUTHOR]

Context. Mass loss from long-period variable stars (LPV) is an important contributor to the evolution of galactic abundances. Dust formation is understood to play an essential role in mass loss. It has, however, proven difficult to develop measurements that strongly constrain the location and timing of dust nucleation and acceleration. Aims. Interferometric imaging has the potential to constrain the geometry and dynamics of mass loss. High angular resolution studies of various types have shown that LPVs have a distinct core-halo structure. These have also shown that LPV images commonly exhibit a non-circular shape. The nature of this shape and its implications are yet to be understood. Methods. Multi-telescope interferometric measurements taken with the Interferometric Optical Telescope Array (IOTA) provide imagery of the LPV Mira in the H-band. This wavelength region is well suited to studying mass loss given the low continuum opacity, which allows for emission to be observed over a very long path in the stellar atmosphere and envelope. Results. The observed visibilities are consistent with a simple core-halo model to represent the central object and the extended molecular layers but, in addition, they demonstrate a substantial asymmetry. An analysis with image reconstruction software shows that the asymmetry is consistent with a localized absorbing patch. The observed opacity is tentatively associated with small dust grains, which will grow substantially during a multi-year ejection process. Spatial information along with a deduced dust content of the cloud, known mass loss rates, and ejection velocities provide evidence for the pulsational pumping of the extended molecular layers. The cloud may be understood as a spatially local zone of enhanced dust formation, very near to the pulsating halo. The observed mass loss could be provided by several such active regions around the star. Conclusions. This result provides an additional clue for better understanding the clumpiness of dust production in the atmosphere of AGB stars. It is compatible with scenarios where the combination of pulsation and convection play a key role in the process of mass loss. [ABSTRACT FROM AUTHOR]