Step-like Increases Research Articles

Extracellular membrane vesicles derived from Komagataeibacter oboediens exposed on the International Space Station fuse with artificial eukaryotic membranes in contrast to vesicles of reference bacterium

Membranous Extracellular Vesicles (EVs) of Gram-negative bacteria are a secretion and delivery system that can disseminate bacterial products and interact with hosts and the environment. EVs of nonpathogenic bacteria deliver their contents by endocytosis into eukaryotic cells, however, no evidence exists for a fusion delivery mechanism. Here, we describe the fusion of exposed to space/Mars-like stressors simulated on the International Space Station vesicles (E-EVs) from Komagataeibacter oboediens to different types of model planar membranes in comparison with the EVs of the ground-based reference strain. The most reliable fusion was achieved with PC:PE:ergosterol or sterol-free PC:PE bilayers. The relative permeability ratio (PK+/PCl-) estimated from the shift of zero current potential according to Goldman–Hodgkin–Katz equation consisted of 4.17 ± 0.48, which coincides with preferential cation selectivity of the EV endogenous channels. The increase in membrane potential from 50 mV to 100 mV induced the fusion of E-EVs with all tested lipid compositions. The fusion of model exosomes with planar bilayer lipid membranes was confirmed by separate step-like increases in its conductance. In contrast, the ground-based reference K. oboediens EVs never induced the fusion event. In our study, we show membrane lipidome perturbations and increased protein aggregation occurred in the exposed samples in the harsh environment when outer membranes of K. oboediens acquired the capability of both homo- and heterotypic fusion possibly by altered membrane fluidity and the pore-forming capability.

Reconstructing five decades of sediment export from two glacierized high-alpine catchments in Tyrol, Austria, using nonparametric regression

Abstract. Knowledge on the response of sediment export to recent climate change in glacierized areas in the European Alps is limited, primarily because long-term records of suspended sediment concentrations (SSCs) are scarce. Here we tested the estimation of sediment export of the past five decades using quantile regression forest (QRF), a nonparametric, multivariate regression based on random forest. The regression builds on short-term records of SSCs and long records of the most important hydroclimatic drivers (discharge, precipitation and air temperature – QPT). We trained independent models for two nested and partially glacier-covered catchments, Vent (98 km2) and Vernagt (11.4 km2), in the upper Ötztal in Tyrol, Austria (1891 to 3772 m a.s.l.), where available QPT records start in 1967 and 1975. To assess temporal extrapolation ability, we used two 2-year SSC datasets at gauge Vernagt, which are almost 20 years apart, for a validation. For Vent, we performed a five-fold cross-validation on the 15 years of SSC measurements. Further, we quantified the number of days where predictors exceeded the range represented in the training dataset, as the inability to extrapolate beyond this range is a known limitation of QRF. Finally, we compared QRF performance to sediment rating curves (SRCs). We analyzed the modeled sediment export time series, the predictors and glacier mass balance data for trends (Mann–Kendall test and Sen's slope estimator) and step-like changes (using the widely applied Pettitt test and a complementary Bayesian approach). Our validation at gauge Vernagt demonstrated that QRF performs well in estimating past daily sediment export (Nash–Sutcliffe efficiency (NSE) of 0.73) and satisfactorily for SSCs (NSE of 0.51), despite the small training dataset. The temporal extrapolation ability of QRF was superior to SRCs, especially in periods with high-SSC events, which demonstrated the ability of QRF to model threshold effects. Days with high SSCs tended to be underestimated, but the effect on annual yields was small. Days with predictor exceedances were rare, indicating a good representativity of the training dataset. Finally, the QRF reconstruction models outperformed SRCs by about 20 percent points of the explained variance. Significant positive trends in the reconstructed annual suspended sediment yields were found at both gauges, with distinct step-like increases around 1981. This was linked to increased glacier melt, which became apparent through step-like increases in discharge at both gauges as well as change points in mass balances of the two largest glaciers in the Vent catchment. We identified exceptionally high July temperatures in 1982 and 1983 as a likely cause. In contrast, we did not find coinciding change points in precipitation. Opposing trends at the two gauges after 1981 suggest different timings of “peak sediment”. We conclude that, given large-enough training datasets, the presented QRF approach is a promising tool with the ability to deepen our understanding of the response of high-alpine areas to decadal climate change.

Signatures of dark excitons in exciton–polariton optics of transition metal dichalcogenides

Integrating 2D materials into high-quality optical microcavities opens the door to fascinating many-particle phenomena including the formation of exciton–polaritons. These are hybrid quasi-particles inheriting properties of both the constituent photons and excitons. In this work, we investigate the so-far overlooked impact of dark excitons on the momentum-resolved absorption spectra of hBN-encapsulated WSe2 and MoSe2 monolayers in the strong-coupling regime. In particular, thanks to the efficient phonon-mediated scattering of polaritons into energetically lower dark exciton states, the absorption of the lower polariton branch in WSe2 is much higher than in MoSe2. It shows unique step-like increases in the momentum-resolved profile indicating opening of specific scattering channels. We study how different externally accessible quantities, such as temperature or mirror reflectance, change the optical response of polaritons. Our study contributes to an improved microscopic understanding of exciton–polaritons and their interaction with phonons, potentially suggesting experiments that could determine the energy of dark exciton states via momentum-resolved polariton absorption.

Merging of relaxations and step-like increase of accompanying supercooled liquid region in metallic glasses via ultrafast nanocalorimetry

Glassy materials under external stimuli usually display multiple and complex relaxations. The relaxations and the evolution paths of glassy materials significantly affect their properties and are closely related to many key issues in glass physics, such as glass transition and thermoplastic forming. However, until now, the relaxation dynamics in the presence of external stimuli and the microscopic atomic motion of glassy materials have been unclear due to the lack of structural information. By combining Flash and conventional differential scanning calorimetry (DSC), we applied a very large range of heating rate of six orders of magnitude and investigated the relaxation dynamics of three typical metallic glasses. We discovered the merging of distinct relaxation events with increasing rate of heating. Most interestingly, the experiments revealed new behaviors with step-like increases in the supercooled liquid region and excess heat capacity during the merging of multiple relaxations. A comprehensive scheme was proposed for the evolution of the thermal relaxation spectrum, the heterogeneity of the corresponding atomic motion and the potential energy landscape with rate of heating. These experimental results shed light on the mechanism of atomic rearrangement during heating and provided a new approach to regulate the physical properties of amorphous materials by controlling their intrinsic relaxation dynamics.

Stepwise evolution of the Asian summer monsoon during the Holocene revealed by a stalagmite record from Heifeng Cave, Southwest China

The abrupt changes of the Asian summer monsoon (ASM) during the Holocene have long been of interest to environmental scientists. Here, RAMPFIT and Bayesian Change Point (BCP) analyses are applied to analyze the stalagmite δ18O record from Heifeng Cave in southern China, and the results show that it is characterized by a distinct stepwise pattern of variation which can be divided into six stages (Stages, S) and five transitional phases (Transitions, T). In the early Holocene, when Northern Hemisphere summer insolation (NHSI) was at its maximum, the ASM underwent step-like increases in strength, comprising two stages. With the decrease in NHSI during the middle to late-Holocene, the weakening of ASM intensity was characterized by further step-like changes comprising three stages. The transitional phases of the monsoon are broadly correlative with millennial-scale monsoon weakening events associated with Bond events in the North Atlantic region, suggesting that the stepwise evolution of the ASM during the Holocene was caused by the combined effects of changes in NHSI and Bond events. We propose that Bond events may have acted as triggers that caused the ASM to cross a critical threshold, prompting a shift from one regime to another.

Quantum size effects in the magnetic susceptibility of a metallic nanoparticle

We theoretically study quantum size effects in the magnetic response of a spherical metallic nanoparticle (e.g. gold). Using the Jellium model in spherical coordinates, we compute the induced magnetic moment and the magnetic susceptibility for a nanoparticle in the presence of a static external magnetic field. Below a critical magnetic field the magnetic response is diamagnetic, whereas above such field the magnetization is characterized by sharp, step-like increases of several tenths of Bohr magnetons, associated with the Zeeman crossing of energy levels above and below the Fermi sea. We quantify the robustness of these regimes against thermal excitations and finite linewidth of the electronic levels. Finally, we propose two methods for experimental detection of the quantum size effects based on the coupling to superconducting quantum interference devices.

Freezing of molecular rotation in a paramagnetic crystal studied by P31 NMR

We present a detailed $^{31}\mathrm{P}$ nuclear magnetic resonance (NMR) study of the molecular rotation in the compound $[\mathrm{Cu}{(\mathrm{pz})}_{2}{(2\ensuremath{-}\mathrm{HOpy})}_{2}]{({\mathrm{PF}}_{6})}_{2}$, where $\mathrm{pz}={\mathrm{C}}_{4}{\mathrm{H}}_{4}{\mathrm{N}}_{2}$ and $2\ensuremath{-}\mathrm{HOpy}={\mathrm{C}}_{5}{\mathrm{H}}_{4}\mathrm{NHO}$. Here, a freezing of the ${\mathrm{PF}}_{6}$ rotation modes is revealed by several steplike increases of the temperature-dependent second spectral moment, with accompanying broad peaks of the longitudinal and transverse nuclear spin-relaxation rates. An analysis based on the Bloembergen-Purcell-Pound (BPP) theory quantifies the related activation energies as ${E}_{a}/{k}_{B}=250$ and 1400 K. Further, the anisotropy of the second spectral moment of the $^{31}\mathrm{P}$ absorption line was calculated for the rigid lattice, as well as in the presence of several sets of ${\mathrm{PF}}_{6}$ reorientation modes, and is in excellent agreement with the experimental data. Whereas the anisotropy of the frequency shift and enhancement of nuclear spin-relaxation rates is driven by the molecular rotation with respect to the dipole fields stemming from the Cu ions, the second spectral moment is determined by the intramolecular interaction of nuclear $^{19}\mathrm{F}$ and $^{31}\mathrm{P}$ moments in the presence of the distinct rotation modes.

Late Quaternary vegetation, climate, and fire history of the Southeast Atlantic Coastal Plain based on a 30,000-yr multi-proxy record from White Pond, South Carolina, USA

AbstractThe patterns and drivers of late Quaternary vegetation dynamics in the southeastern United States are poorly understood due to low site density, problematic chronologies, and a paucity of independent paleoclimate proxy records. We present a well-dated (15 accelerator mass spectrometry14C dates) 30,000-yr record from White Pond, South Carolina that consists of high-resolution analyses of fossil pollen, macroscopic charcoal, andSporormiellaspores, and an independent paleotemperature reconstruction based on branched glycerol dialkyl tetraethers. Between 30,000 and 20,000 cal yr BP, openPinus-Piceaforest grew under cold and dry conditions; elevatedQuercusbefore 26,000 cal yr BP, however, suggest warmer conditions in the Southeast before the last glacial maximum, possibly corresponding to regionally warmer conditions associated with Heinrich event H2. Warming between 19,700 and 10,400 cal yr BP was accompanied by a transition from conifer-dominated to mesic hardwood forest.Sporormiellaspores were not detected and charcoal was low during the late glacial period, suggesting megaherbivore grazers and fire were not locally important agents of vegetation change.Pinusreturned to dominance during the Holocene, with step-like increases inPinusat 10,400 and 6400 cal yr BP, while charcoal abundance increased tenfold, likely due to increased biomass burning associated with warmer conditions. Low-intensity surface fires increased after 1200 cal yr BP, possibly related to the establishment of the Mississippian culture in the Southeast.

Second-order modeling for the pulmonary oxygen uptake on-kinetics: a comprehensive solution for overshooting and nonovershooting responses to exercise.

The human oxygen uptake (V̇o2) response to step-like increases in work rate is currently modeled by a First Order System Multi-Exponential (FOME) arrangement. Because of their first-order nature, none of FOME model's exponentials is able to model an overshoot in the oxygen uptake kinetics (OV̇o2K). Nevertheless, OV̇o2K phenomena are observed in the fundamental component of trained individuals' step responses. We hypothesized that a Mixed Multi-Exponential (MiME) model, where the fundamental component is modeled with a second- instead of a first-order system, would present a better overall performance than that of the traditional FOME model in fitting V̇o2 on-kinetics at all work rates, either presenting or not OV̇o2K. Fourteen well-trained male cyclists performed three step on-transitions at each of three work rates below their individual lactate thresholds' work rate (WRLT), and two step on-transitions at each of two exercise intensities above WRLT. Averaged responses for each work rate were fitted with MiME and FOME models. Root mean standard errors were used for comparisons between fitting performances. Additionally, a methodology for detecting and quantifying OV̇o2K phenomena is proposed. Second order solutions performed better (P < 0.000) than the first-order exponential when the OV̇o2K was present, and did not differ statistically (P = 0.973) in its absence. OV̇o2K occurrences were observed below and, for the first time, above WRLT (88 and 7%, respectively). We concluded that the MiME model is more adequate and comprehensive than the FOME model in explaining V̇o2 step on-transient responses, considering cases with or without OV̇o2K altogether.NEW & NOTEWORTHY To our knowledge, this is the first study applying second-order system equations to model V̇o2 on-kinetics, which is useful for both mathematical representation and physiological understanding of the overshoot phenomenon manifesting in the fundamental components of some step responses. Moreover, an objective methodology for detecting and quantifying this overshoot that considers data from the whole response is proposed. Finally, this is the first work detecting overshoot occurrences outside the moderate domain of exercise.

Structure and electric properties of NaxLa(2−x)/3Cu3Ti4O12 ceramics prepared by sol–gel method

The NaxLa(2−x)/3Cu3Ti4O12 (x = 0.50, 0.35, 0.20, 0.05) ceramics were designed on the premise of charge balance and were prepared by the sol–gel method. The phase structure, microstructure, electric properties of the NaxLa(2−x)/3Cu3Ti4O12 (x = 0.50, 0.35, 0.20, 0.05) ceramics were investigated. The results indicated that with the decreasing of x, the NaxLa(2−x)/3Cu3Ti4O12 (x = 0.50, 0.35, 0.20, 0.05) ceramics showed different microstructure and electrical behaviors. When x = 0.35, the NaxLa(2−x)/3Cu3Ti4O12 ceramics showed the biggest dielectric constant, but still kept the lower dielectric losses. When x = 0.20 and 0.05, the dielectric losses of NaxLa(2−x)/3Cu3Ti4O12 (x = 0.20, 0.05) ceramics were decreased, which were consistent with the primary aim of the present study. However, the dielectric constant of NaxLa(2−x)/3Cu3Ti4O12 (x = 0.20, 0.05) ceramics also were decreased, which was an unwanted result. In addition, with the decreasing of x, the second step-like increases and small peaks (A2) in the curses of dielectric constant-temperature, and the second relaxation peaks (a2) in the electric modulus analysis gradually weaken and finally disappeared. The conduction characteristics of NaxLa(2−x)/3Cu3Ti4O12 (x = 0.50, 0.35, 0.20, 0.05) ceramics had changed from two linear area to a linear area. Interestingly, when x = 0.35, the second relaxation energy values of NaxLa(2−x)/3Cu3Ti4O12 were relatively small and even much smaller than the first relaxation activation energy values, and the first relaxation activation energy value and second relaxation activation energy value were less than 0.70 eV, which might be attributed to the same role of the first ionization of oxygen vacancies, which were different from other ceramics. From the above the results of research, on the premise of charge balance, with change of Na+ and La3+ content, different the microstructure and electrical behavior of NaxLa(2−x)/3Cu3Ti4O12 ceramics might be due to the different defect structure.

Outbreaks of a Presumed Infectious Pathogen Creating On/Off Switching in Deaths

Background: There is now increasing international evidence for a series of outbreaks of a presumed infectious pathogen which result in 12-month periods of higher deaths, medical admissions, sickness absence, higher gender ratio at birth, stillbirths and certain congenital abnormalities. This study investigates the increase in deaths accompanying these outbreaks in the UK. Methods: Monthly deaths for local government areas in the UK were analysed using a running (moving) 12-month total. The magnitude of sudden step-like increases in deaths were calculated by comparing successive 12-month periods. Results: Statistically significant and large increases in death are observed at approximate 2-year intervals across all local government geographies. Such local ‘outbreaks’ aggregate to give periods of higher regional and national deaths. Conclusion: A new type of infectious outbreak appears to have been identified, with the potential for a profound change in public health policy. The immune modifying virus cytomegalovirus can be circumstantially implicated.

Inter-ribbon tunneling in graphene: An atomistic Bardeen approach

A weakly coupled system of two crossed graphene nanoribbons exhibits direct tunneling due to the overlap of the wavefunctions of both ribbons. We apply the Bardeen transfer Hamiltonian formalism, using atomistic band structure calculations to account for the effect of the atomic structure on the tunneling process. The strong quantum-size confinement of the nanoribbons is mirrored by the one-dimensional character of the electronic structure, resulting in properties that differ significantly from the case of inter-layer tunneling, where tunneling occurs between bulk two-dimensional graphene sheets. The current-voltage characteristics of the inter-ribbon tunneling structures exhibit resonance, as well as stepwise increases in current. Both features are caused by the energetic alignment of one-dimensional peaks in the density-of-states of the ribbons. Resonant tunneling occurs if the sign of the curvature of the coupled energy bands is equal, whereas a step-like increase in the current occurs if the signs are opposite. Changing the doping modulates the onset-voltage of the effects as well as their magnitude. Doping through electrostatic gating makes these structures promising for application towards steep slope switching devices. Using the atomistic empirical pseudopotentials based Bardeen transfer Hamiltonian method, inter-ribbon tunneling can be studied for the whole range of two-dimensional materials, such as transition metal dichalcogenides. The effects of resonance and of step-like increases in the current we observe in graphene ribbons are also expected in ribbons made from these alternative two-dimensional materials, because these effects are manifestations of the one-dimensional character of the density-of-states.

Nanosecond Characterization of Regional Domain Imprint from Fast Domain Switching Currents in Pb(Zr,Ti)O3 Thin Films**Supported by the National Key Basic Research Program of China under Grant No 2014CB921004, the National Natural Science Foundation of China under Grant Nos 61225020 and 61176121, and the Program for Professor of Special Appointment (Eastern Scholar) in Shanghai.

The traditional imprint characterization of ferroelectric thin films estimates imprint time dependence of the mean coercive voltage of all domains from a polarization-voltage hysteresis loop, which shows a semilogarithmic time dependence above an initial imprint time of τ0 > 1 μs at room temperature. Below τ0, the imprint effect is believed to be weak. In consideration of region-by-region domain reversal under a rising pulsed voltage with ordered coercive voltages increasing from zero up to the maximum applied voltage during capacitor charging time, we can estimate the imprinted coercive voltage of each domain from domain switching current transient separately with imprint time as short as 20 ns. In disagreement with the previous observations, all imprinted coercive voltages for the domains in Pt/Pb(Zr0.4Ti0.6)O3/Pt thin-film capacitors show step-like increases at two characteristic times of 300 ns and 0.27s. The imprint effect is surprisingly strong enough even at shortened time down to 20 ns without any evidence of weakening.

The real reason for the huge NHS overspend?

40 British Journal of Healthcare Management 2016 Vol 22 No 1 © 2 01 6 M A H ea lth ca re L td behaviour is effectively removed and small number monthly variation is minimised. The periods of high unexplained death shows up in a running 12-month total as an inverted ‘V’, where the upward slope represents a step-like increase in deaths lasting for somewhere around 12 months, and the downward slope simply shows the dilution of the running total after cessation of the step-change. The magnitude of the step-change is shown by the difference from trough to peak and, as can be seen in Figure 1 can be very large or even seemingly absent on some occasions. Differences in timing between local government areas can be discerned, and these differences arise from very small area spatial spread of an as yet unidentified agent (Jones, 2015c-f). Increased medical admissions and bed occupancy mirrors the increase in deaths (Jones, 2015b; 2015h–i; 2016). Figure 1 illustrates the principle that something strange—probably infectious–is happening, which affects levels of medical admission and costs. Also note that the funding formula does not contain any correcting factors to account for this behaviour (Jones, 2013). Table 1 quantifies the magnitude of these step-like increases in death for a variety of the largest regions (in italics) and counties during a number of these suspected infectious outbreaks. Both maximum step-up and step-down are shown in the last two columns simply because the value of the step-down gives an alternative measure for the strength of each event. Immediately apparent is a wide range in percentage increases between regions for each event, with the 2004 (and to a lesser extent 2002) event being below the limit of detection (n/a) in a range of locations. Generally speaking, the 2012 and 2014 events are the highest in magnitude, with 60% of all local government areas in England and Wales having the greatest magnitude of increase in deaths (and hence medical admissions) in 2014, and as such will have the greatest impact upon NHS financial pressures. However, the principle observation is that different locations will experience different cost pressures, such as Essex (+5.4%) in the 2010 event versus +0.6% in Rod Jones The real reason for the huge NHS overspend?

A regular series of unexpected and large increases in total deaths (all-cause mortality) for male and female residents of mid super output areas (MSOA) in England and Wales: How high level analysis can miss the contribution from complex small-area spatial spread of a presumed infectious agent

Background: The trends in death in the UK, Europe, Australia, New Zealand and America show evidence for extended periods of higher than expected deaths. This study investigates the detail of these trends using Mid Super Output Areas (MSOA) in England and Wales, containing 10 to 100 male or female deaths per annum. Objective: To study the trend in deaths for both male and female residents of MSOA, and seek to identify a recurring series of curious and unexpected step-like increases in death which endure for around 12-months before abating. Methods: A running 12-month sum of deaths was constructed for each MSOA over the period Jan-01 to Dec-14. Blocks of 12-month deaths were compared each side of a given date to detect step-like increases in deaths which endure for a period of around 12 months before reverting back to the baseline level. Results: Deaths in each MSOA are marked by a regular series of step-like increases which initiate at roughly two year intervals, however across England and Wales around 1% of MSOA initiate a maximum magnitude event at any point in time. When clustered to larger areas, depending on the timing (synchrony) and magnitude in the smaller areas, these events can cause either a cancelling-out effect or re-inforce each other to create larger local, regional or national events. Female deaths show a tendency for larger step-like increases than males. The maximum increase in deaths declines with increasing size of the MSOA (average deaths per annum) and follows a Power Law function. For MSOA containing around 10 deaths per annum, the largest step-like increase in deaths range from 58% to 300%. Extrapolation back to around 0.1 deaths (roughly 8 households or a small social network) gives a maximum potential increase around 1,000%. Males and females appear to behave as separate compartments and each can lag behind the other due to random events surrounding initiation of each ‘outbreak’. Other studies indicate that these events instigate periods of higher emergency department attendance, emergency medical admissions, GP referral and sickness absence, and even a wobble in the gender ratio at birth. Conclusions: These events provide evidence for the existence of a new type of disease entity. There are implications to the monitoring of deaths and mortality rates between areas and countries, most importantly that the unique spatiotemporal spread can lead to these events being obscured in larger aggregates such as a country or region. The larger increase in death in females is also reflected in larger increases in female medical admissions during these events, and seeming selective loss of the female fetus. It remains unknown why there is an approximate two-year periodicity, and why the magnitude of each event in each MSOA shows such high variation over time, although chance transmission and a moderate degree of seasonal forcing (winter) appear involved.

Calmodulation of Voltage-Gated Calcium Channels by Blue Light

Delivering custom-shaped signaling inputs to dissect biological networks has been a coveted goal of engineering-minded biologists, keenly aware of the advantages of analyzing electronic circuitry with a signal generator. We have recently devised a rapamycin-based chemical-dimerization strategy to produce step-like increases in the concentration of calmodulin (CaM) at the cytoplasmic mouth of L-type Ca2+ channels. This tactic revealed that CaM binding to channels induces two effects: a large increase in peak open probability (PO), and the ability to undergo Ca2+-dependent inactivation (CDI) (Adams et al (2014) Cell, in press). Yet, the rapamycin system is comparatively slow (trise-half ∼30 s) and irreversible. Here we explore the use of a light-based dimerization system from Arabidopsis (CRY2 and CIB1, Kennedy et al (2010)) to deliver CaM more rapidly and reversibly upon activation by blue light. To evaluate functionality with Ca2+ channels, HEK293 cells expressing Ltype Cav1.3 channels were endowed with CIB1 targeted to the membrane and CRY2 glycine linked to a dominant-negative CaM1234, where mutations eliminate Ca2+ binding and presumably render this construct a constitutive apoCaM. On dimerization with blue light, CDI was indeed attenuated, confirming functionality with Ca2+ channels. More telling, blue-light exposure left peak currents unchanged, arguing that CaM1234 in fact acts just like apoCaM. Next, we expressed a variant of Cav1.3 (MQDY) with diminished apoCaM binding at baseline, and changed the CIB1 payload to wild-type CaM. Reassuringly, blue-light exposure increased both peak current and CDI by ∼20% (5/6 responding cells), consistent with enhanced MQDY binding to CaM upon blue-light recruitment. Intriguingly, full enhancement occured in the very first current evoked after blue-light illumination (<20 s); CaM exchange with these channels thereby occurs on an even faster timescale. In all, light-based recruitment promises a powerful tool for investigating CaM modulation of membrane proteins.

Heterogeneity in signaled active avoidance learning: substantive and methodological relevance of diversity in instrumental defensive responses to threat cues.

Individuals exposed to traumatic stressors follow divergent patterns including resilience and chronic stress. However, researchers utilizing animal models that examine learned or instrumental threat responses thought to have translational relevance for Posttraumatic Stress Disorder (PTSD) and resilience typically use central tendency statistics that assume population homogeneity. This approach potentially overlooks fundamental differences that can explain human diversity in response to traumatic stressors. The current study tests this assumption by identifying and replicating common heterogeneous patterns of response to signaled active avoidance (AA) training. In this paradigm, rats are trained to prevent an aversive outcome (shock) by performing a learned instrumental behavior (shuttling between chambers) during the presentation of a conditioned threat cue (tone). We test the hypothesis that heterogeneous trajectories of threat avoidance provide more accurate model fit compared to a single mean trajectory in two separate studies. Study 1 conducted 3 days of signaled AA training (n = 81 animals) and study 2 conducted 5 days of training (n = 186 animals). We found that four trajectories in both samples provided the strongest model fit. Identified populations included animals that acquired and retained avoidance behavior on the first day (Rapid Avoiders: 22 and 25%); those who never successfully acquired avoidance (Non-Avoiders; 20 and 16%); a modal class who acquired avoidance over 3 days (Modal Avoiders; 37 and 50%); and a population who demonstrated a slow pattern of avoidance, failed to fully acquire avoidance in study 1 and did acquire avoidance on days 4 and 5 in study 2 (Slow Avoiders; 22.0 and 9%). With the exception of the Slow Avoiders in Study 1, populations that acquired demonstrated rapid step-like increases leading to asymptotic levels of avoidance. These findings indicate that avoidance responses are heterogeneous in a way that may be informative for understanding both resilience and PTSD as well as the nature of instrumental behavior acquisition. Characterizing heterogeneous populations based on their response to threat cues would increase the accuracy and translatability of such models and potentially lead to new discoveries that explain diversity in instrumental defensive responses.

Control of motor unit firing during step-like increases in voluntary force.

In most skeletal muscles, force is generated by a combination of motor unit (MU) recruitment and increases in the firing rate of previously active MUs. Two contrasting patterns of firing rate organization have been reported. In the first pattern, the earliest recruited MUs reach the highest firing rates as force is increased, and later recruited MUs fire at lower rates. When firing rate of multiple MUs are superimposed, these rate trajectories form a concentric layered profile termed “onion skin.” In the second pattern, called “reverse onion skin,” later recruited MUs reach higher firing rates, and crossing of firing rate trajectories for recorded MUs is common (although such trajectories are assembled routinely from different trials). Our present study examined the firing rate organization of concurrently active MUs of the first dorsal interosseous muscle during serial, step-like increases in isometric abduction forces. We used a surface sensor array coupled with MU discrimination algorithms to characterize MU firing patterns. Our objective was to determine whether “onion skin” profiles are contingent upon the force trajectory of the motor task, examined here using step-like increases of force output, and also whether they are manifested at different force levels. Our results revealed that the overall “onion skin” firing rate profile was retained as the force level increased with each force step up to 15% MVC. However, the distribution of firing rates across MUs was compressed with increasing force, and overlapping firing rate of units were observed. This rate compression was largely due to rate saturation of the relatively high frequency discharging MUs. Our results reflect flexible firing patterns across MUs at different levels of excitation drive. It is also evident that many units did not follow all the step increases consistently. This failure to track firing rate increases at higher forces could be due to an intrinsically mediated saturation of firing rates for the low threshold MUs, or potentially to some form of inhibitory interactions between active MUs as the level of excitation of the MU pool is progressively increased.

GALACTIC COSMIC-RAY MODULATION NEAR THE HELIOPAUSE

We investigate the modulation of galactic cosmic rays in the inner and outer heliosheaths using three-dimensional numerical simulations. The model is based on the Parker transport equation integrated using a stochastic phase-space trajectory method. Integration is performed on a plasma background obtained from a global three-dimensional magnetohydrodynamic simulations. Our results predict a negligible amount of modulation in the outer heliosheath because of weak scattering of cosmic ray ions owing to very low levels of magnetic fluctuation power at wavenumbers relevant to the transport of cosmic rays with MeV to GeV energies. This means that the heliopause may be treated as a Dirichlet-type boundary for the purpose of energetic particle modeling. We present models with and without drift velocity to facilitate comparison with papers published earlier. We also attempt to reproduce the sudden step-like increases of cosmic-ray intensity observed by Voyager 1 before its encounter with the heliopause. Our results indicate that very slow cross-field diffusion in the outer heliosheath could produce a large gradient of cosmic rays inside the heliospheric boundary. The resulting large gradient in cosmic-ray intensity near the heliopause qualitatively agrees with recent Voyager 1 observations.

Surface wave excitation at the northern edge of the Kanto Basin, Japan

In this paper, we analyze the seismograms of a local earthquake (M W = 5.8) and find a clear surface wave excitation at the northern edge of the Kanto Basin, Japan. To conduct three-dimensional (3-D) finite difference method simulations for this observation, we investigate the characteristics of the S wave velocity in the Kanto Basin and construct a realistic sedimentary structure model. The S wave velocities derived from the vertical seismic profiling measurements in the Kanto Basin show smooth depth gradients rather than step-like increases and can be successfully modeled by an exponential asymptotically bounded velocity function. Our simulation using the modified Japan integrated velocity structure model by incorporating a sedimentary layer with S wave velocity-depth gradients well reproduces the excitation and dispersion of the observed surface waves. This result indicates that realistic modeling of the impedance contrast at the sediment-bedrock interface is indispensable for the precise evaluation of surface wave excitation at the basin edge.