Transition Path Sampling and Forward Flux Sampling. Applications to Biological Systems.

The last decade has seen a rapid growth in the number of simulation methods and applications dealing with the sampling of transition pathways of rare nanoscale events. Such studies are crucial, for example, for understanding the mechanism and kinetics of conformational transitions and enzymatic events associated with the function of biomolecules. In this review, a broad account of transition path sampling approaches is provided, starting from the general concepts, progressing to the specific principles that underlie some of the most important methods, and eventually singling out the so-called forward flux sampling method for a more detailed description. This is done because forward flux sampling, despite its appealing simplicity and potential efficiency, has thus far received limited attention from practitioners. While path sampling methods have a widespread application to many types of rare transitional events, here only recent applications involving biomolecules are reviewed, including isomerization, protein folding, and enzyme catalysis.This publication is based on work supported in part by Award No. KUS-C1-018-02, made by King Abdullah University of Science and Technology (KAUST). Additional support from the National Science Foundation Award 0553719 is also gratefully acknowledged. The authors are also grateful to J. Hernandez-Ortiz and P. Bolhuis for allowing us to modify their picture files

THE CONODONTS FROM THE EL HÍGADO FORMATION AND ITS CONTRIBUTION TO THE KNOWL-EDGE OF METAMORPHISM AND ORDOVICIAN PALEOGEOGRAPHY IN THE CENTRAL CORDILLERA OF COLOMBIA

En la Formación El Hígado aforante en la vertiente oriental de la Serranía de Las Minas, a 9.5 km al NW del municipio de Tarqui (Departamento del Huila), se encontró en su miembro inferior, en niveles de caliza bioclástica formados por acumulaciones lumaquélicas de braquiópodos rinconeliformes, una asociación de conodontos del Ordovícico Medio, junto con microelementos reelaborados del Ordovícico Inferior y Medio basal. El conjunto involucra una mezcla tafonómica de dos o más horizontes ordovícicos. Las formas más antiguas son de edad Tremadociano (biozonas de Paltodus deltifer a Paroistodus proteus). El rango de la asociación más moderna abarca las biozonas de Lenodus variabilis a Eoplacognathus suecicus y es de edad Darriwiliano. Otras formas retrabajadas parecen sugerir asociaciones adicionales de edades Floiano, Piso Tercero y Darriwiliano basal. El descubrimiento de estos conodontos implica que el Tremadociano llegó a depositarse en esta zona y fue erosionado prácticamente in situ en tiempos arenigianos, por lo que el Terreno Chibcha ya quedaría adyacente por aquél entonces a la cuenca pericratónica del este de Colombia. El índice de alteración del color de los co-nodontos (CAI), con valores 2 a 4, descarta el metamorfsmo regional de la Formación El Hígado, afectada localmente por hidrotermalismo (CAI 6).   Palabras clave: Conodontos, Ordovícico, Cordillera Central de Colombia, Metamorfsmo, Paleogeografía      Conodonts are rare fossils in northern South America, and this work reports their frst occurrence in the Ordovician of Colombia. The studied sample come from a thin brachiopod coquina interstratifed in storm-generated sandstone deposits, 20 m above the base of the El Hígado Formation (Darriwilian) in its type section in the Central Cordillera. The conodont assemblage contains fairly well preserved elements with different states of mechanical fragmentation, corrosion and even bacterial alteration. CAI values are between 2 and 6, in absence of regional metamorphism and with evidence of local hydrothermalism. The sample involved a taphonomic mixture of two or more Ordovician horizons. The older conodont assemblage is of Tremadocian age and range from the Paltodus deltifer to the Paroistodus proteus conodont biozones. The youngest assemblage range through the Lenodus variabilis and Eoplacognathus suecicus conodont biozones and is of Darriwilian age. A number of reworked conodont taxa seem to suggest additional assemblages of Floian, Third Stage and lowest Darriwilian intermediate ages. The studied conodonts indicate the existence of older and previously unknown Ordovician sedimentation in Central Colombia, where reworked specimens were probably winnowed from condensed successions ranging from the lower Tremadocian to the lower Darriwilian, and are indicative of a pre-Ordovician accretion fro the Chibcha terrane.   Key words: Conodonts, Ordovician, Central Cordillera of Colombia, Metamorphism, Palaeogeography.   &nbsp

Detection of Gravitational Redshift on the Solar Disk by Using Iodine-Cell Technique

With an aim to examine whether the predicted solar gravitational redshift can be observationally confirmed under the influence of the convective Doppler shift due to granular motions, we attempted measuring the absolute spectral line-shifts on a large number of points over the solar disk based on an extensive set of 5188-5212A region spectra taken through an iodine-cell with the Solar Domeless Telescope at Hida Observatory. The resulting heliocentric line shifts at the meridian line (where no rotational shift exists), which were derived by finding the best-fit parameterized model spectrum with the observed spectrum and corrected for the earth's motion, turned out to be weakly position-dependent as ~ +400 m/s near the disk center and increasing toward the limb up to ~ +600 m/s (both with a standard deviation of sigma ~ 100 m/s). Interestingly, this trend tends to disappear when the convectiveshift due to granular motions (~-300 m/s at the disk center and increasing toward the limb; simulated based on the two-component model along with the empirical center-to-limb variation) is subtracted, finally resulting in the averaged shift of 698 m/s (sigma = 113 m/s). Considering the ambiguities involved in the absolute wavelength calibration or in the correction due to convective Doppler shifts (at least several tens m/s, or more likely up to <~100 m/s), we may regard that this value is well consistent with the expected gravitational redshift of 633 m/s.Comment: 28 pages, 12 figures, electronic materials as ancillary data (table3, table 4, ReadMe); accepted for publication in Solar Physic

VFISV: Very Fast Inversion of the Stokes Vector for the Helioseismic and Magnetic Imager

In this paper we describe in detail the implementation and main properties of a new inversion code for the polarized radiative transfer equation (VFISV: Very Fast inversion of the Stokes vector). VFISV will routinely analyze pipeline data from the Helioseismic and Magnetic Imager (HMI) on-board of the Solar Dynamics Observatory (SDO). It will provide full-disk maps (4096$\times$4096 pixels) of the magnetic field vector on the Solar Photosphere every 10 minutes. For this reason VFISV is optimized to achieve an inversion speed that will allow it to invert 16 million pixels every 10 minutes with a modest number (approx. 50) of CPUs. Here we focus on describing a number of important details, simplifications and tweaks that have allowed us to significantly speed up the inversion process. We also give details on tests performed with data from the spectropolarimeter on-board of the Hinode spacecraft.Comment: 23 pages, 9 figures (2 color). Submitted for publication to Solar Physic

Temporal evolution of the Evershed flow in sunspots. I. Observational characterization of Evershed clouds

[Abridged] The magnetic and kinematic properties of the photospheric Evershed flow are relatively well known, but we are still far from a complete understanding of its nature. The evolution of the flow with time, which is mainly due to appearance of velocity packets called Evershed clouds (ECs), may provide information to further constrain its origin. Here we undertake a detailed analysis of the evolution of the Evershed flow by studying the properties of ECs. In this first paper we determine the sizes, proper motions, location in the penumbra, and frequency of appearance of ECs, as well as their typical Doppler velocities, linear and circular polarization signals, Stokes V area asymmetries, and continuum intensities. High-cadence, high-resolution, full vector spectropolarimetric measurements in visible and infrared lines are used to derive these parameters. We find that ECs appear in the mid penumbra and propage outward along filaments with large linear polarization signals and enhanced Evershed flows. The frequency of appearance of ECs varies between 15 and 40 minutes in different filaments. ECs exhibit the largest Doppler velocities and linear-to-circular polarization ratios of the whole penumbra. In addition, lines formed deeper in the atmosphere show larger Doppler velocities, much in the same way as the ''quiescent'' Evershed flow. According to our observations, ECs can be classified in two groups: type I ECs, which vanish in the outer penumbra, and type II ECs, which cross the outer penumbral boundary and enter the sunspot moat. Most of the observed ECs belong to type I. On average, type II ECs can be detected as velocity structures outside of the spot for only about 14 min. Their proper motions in the moat are significantly reduced with respect to the ones they had in the penumbra.Comment: Accepted for publication in A&

Modelling and Interpreting The Effects of Spatial Resolution on Solar Magnetic Field Maps

Different methods for simulating the effects of spatial resolution on magnetic field maps are compared, including those commonly used for inter-instrument comparisons. The investigation first uses synthetic data, and the results are confirmed with {\it Hinode}/SpectroPolarimeter data. Four methods are examined, one which manipulates the Stokes spectra to simulate spatial-resolution degradation, and three "post-facto" methods where the magnetic field maps are manipulated directly. Throughout, statistical comparisons of the degraded maps with the originals serve to quantify the outcomes. Overall, we find that areas with inferred magnetic fill fractions close to unity may be insensitive to optical spatial resolution; areas of sub-unity fill fractions are very sensitive. Trends with worsening spatial resolution can include increased average field strength, lower total flux, and a field vector oriented closer to the line of sight. Further-derived quantities such as vertical current density show variations even in areas of high average magnetic fill-fraction. In short, unresolved maps fail to represent the distribution of the underlying unresolved fields, and the "post-facto" methods generally do not reproduce the effects of a smaller telescope aperture. It is argued that selecting a method in order to reconcile disparate spatial resolution effects should depend on the goal, as one method may better preserve the field distribution, while another can reproduce spatial resolution degradation. The results presented should help direct future inter-instrument comparisons.Comment: Accepted for publication in Solar Physics. The final publication (including full-resolution figures) will be available at http://www.springerlink.co

Sunspots: from small-scale inhomogeneities towards a global theory

The penumbra of a sunspot is a fascinating phenomenon featuring complex velocity and magnetic fields. It challenges both our understanding of radiative magneto-convection and our means to measure and derive the actual geometry of the magnetic and velocity fields. In this contribution we attempt to summarize the present state-of-the-art from an observational and a theoretical perspective.Comment: Accepted for publication in Space Science Review

Modeling the Subsurface Structure of Sunspots

While sunspots are easily observed at the solar surface, determining their subsurface structure is not trivial. There are two main hypotheses for the subsurface structure of sunspots: the monolithic model and the cluster model. Local helioseismology is the only means by which we can investigate subphotospheric structure. However, as current linear inversion techniques do not yet allow helioseismology to probe the internal structure with sufficient confidence to distinguish between the monolith and cluster models, the development of physically realistic sunspot models are a priority for helioseismologists. This is because they are not only important indicators of the variety of physical effects that may influence helioseismic inferences in active regions, but they also enable detailed assessments of the validity of helioseismic interpretations through numerical forward modeling. In this paper, we provide a critical review of the existing sunspot models and an overview of numerical methods employed to model wave propagation through model sunspots. We then carry out an helioseismic analysis of the sunspot in Active Region 9787 and address the serious inconsistencies uncovered by \citeauthor{gizonetal2009}~(\citeyear{gizonetal2009,gizonetal2009a}). We find that this sunspot is most probably associated with a shallow, positive wave-speed perturbation (unlike the traditional two-layer model) and that travel-time measurements are consistent with a horizontal outflow in the surrounding moat.Comment: 73 pages, 19 figures, accepted by Solar Physic

Insights on the source of the 28 September 2018 Sulawesi tsunami, Indonesia based on spectral analyses and numerical simulations

The 28 September 2018 Sulawesi tsunami has been a puzzle because extreme deadly tsunami waves were generated following an Mw 7.5 strike-slip earthquake, while such earthquakes are not usually considered to produce large tsunamis. Here, we obtained, processed and analyzed two sea level records of the tsunami in the near-field (Pantoloan located inside the Palu Bay) and far-field (Mamuju located outside the Palu Bay) and conducted numerical simulations to shed light on the tsunami source. The two tide gauges recorded maximum tsunami trough-to-crest heights of 380 and 24 cm, respectively, with respective dominating wave periods of 3.6-4.4 and 10 min, and respective high-energy wave duration of 5.5 and [14 h. The two observed waveforms were significantly different with wave amplitude and period ratios of *16 and *3, respectively. We infer tsunamigenic source dimen19 sions of 3.4–4.1 km and 32.5 km, for inside and outside of the Palu Bay, respectively. Our numerical simulations fairly well repro21 duced both tsunami observations in Pantoloan and Mamuju; except for the arrival time in Mamuju. However, it was incapable of reproducing the maximum reported coastal amplitudes of 6–11 m. It is possible that these two sources are different parts of the same tectonic source. A bay oscillation mode of *85 min was revealed for the Palu Bay through numerical modeling. Actual sea surface disturbances and landslide-generated waves were captured by two video recordings from inside the Palu Bay shortly after the earthquake. It is possible that a large submarine landslide contributed to and intensified the Sulawesi tsunami. We identify the southern part of the Palu Bay, around the latitude of -0.82o S, as the most likely location of a potential landslide based on our backward tsunami ray tracing analysis. However, marine geological data from the Palu Bay are required to confirm such hypothesis

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men