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The tunable design of protein redox potentials promises to open a range of applications in biotechnology and catalysis. Here, we introduce a method to calculate redox potential changes by combining fluctuation relations with molecular dynamics simulations. It involves the simulation of reduced and oxidized states, followed by the instantaneous conversion between them. Energy differences introduced by the perturbations are obtained using the Kubo-Onsager approach. Using a detailed fluctuation relation coupled with Bayesian inference, these are postprocessed into estimates for the redox potentials in an efficient manner. This new method, denoted MD + CB, is tested on a de novofour-helix bundle heme protein (the m4D2 “maquette”) and five designed mutants, including some mutants characterized experimentally in this work. The MD + CB approach is found to perform reliably, giving redox potential shifts with reasonably good correlation (0.85) to the experimental values for the mutants. The MD + CB approach also compares well with redox potential shift predictions using a continuum electrostatic method. The estimation method employed within the MD + CB approach is straightforwardly transferable to standard equilibrium MD simulations and holds promise for redox protein engineering and design applications.

The Global‐scale Observations of Limb and Disk (GOLD) imagers scan the Earth's Thermosphere‐Ionosphere (TI) in the far ultraviolet wavelengths. Measurements from GOLD daylit spectrum are used to retrieve the column integrated atomic oxygen to molecular nitrogen density ratio (O/N2) over about one fourth of the globe. The present investigation assesses the impact of assimilating GOLD disk O/N2on the Whole Atmosphere Community Climate Model with thermosphere‐ionosphere eXtension (WACCMX) using the Data Assimilation Research Testbed (DART) ensemble adjustment Kalman filter. Two Observing System Simulation Experiments (OSSEs) are performed, and improvements are quantified by calculating root mean square error (RMSE) and bias with respect to a truth run. In addition to solar and geomagnetic forcing, we introduced gravity wave forcing perturbations to increase the ensemble spread, which has not previously been applied in ensemble assimilation. One of the OSSEs assimilates only the lower atmosphere (LA, <${< } $100 km) observations, referred to as LA experiment, and the second assimilates GOLD O/N2and LA observations, referred to as Whole Atmosphere (WA) experiment. The WA‐analysis O/N2RMSE and bias are about 60% and 87% better compared to LA‐analysis. Also, the O/N2RMSE and bias for the WA‐analysis are about 23% and 54% better compared to WA 1‐hr forecasts. The improvement in WA electron column density (ECD), a model equivalent of Total Electron Content (TEC), is about 24% compared to the LA experiment. These results demonstrate that the assimilation of GOLD O/N2improves both the thermosphere and ionosphere in a whole atmosphere data assimilation system. To be able to nowcast and forecast the Thermosphere‐Ionosphere (TI) weather we need to demonstrate that the currently available whole atmosphere‐ionosphere‐thermosphere model results can be improved by adjusting their states based on the available observations. In this work we demonstrate a potential scenario, by employing Observing System Simulation Experiments (OSSE), where the use of NASA GOLD mission column integrated ratio of atomic oxygen to molecular nitrogen (O/N2) improves the analysis and short term forecast states in the Whole Atmosphere Community Climate Model with thermosphere‐ionosphere eXtension (WACCMX) compared to only assimilating observations below ∼${\sim} $100 km. These improvements suggest that assimilation of GOLD observations can be potentially beneficial to space weather forecasting models. Synthetic GOLD disk O/N2observations are assimilated in WACCMX + DARTGravity wave forcing perturbations are introduced to improve the ensemble spreadThe assimilation improves analysis RMSE and bias in O/N2by 23%–60% and 54%–87%, depending on the reference chosen Synthetic GOLD disk O/N2observations are assimilated in WACCMX + DART Gravity wave forcing perturbations are introduced to improve the ensemble spread The assimilation improves analysis RMSE and bias in O/N2by 23%–60% and 54%–87%, depending on the reference chosen

Activation heat capacity is emerging as a crucial factor in enzyme thermoadaptation, as shown by the non-Arrhenius behaviour of many natural enzymes. However, its physical origin and relationship to the evolution of catalytic activity remain uncertain. Here we show that directed evolution of a computationally designed Kemp eliminase reshapes protein dynamics, which gives rise to an activation heat capacity absent in the original design. These changes buttress transition-state stabilization. Extensive molecular dynamics simulations show that evolution results in the closure of solvent-exposed loops and a better packing of the active site. Remarkably, this gives rise to a correlated dynamical network that involves the transition state and large parts of the protein. This network tightens the transition-state ensemble, which induces a negative activation heat capacity and non-linearity in the activity–temperature dependence. Our results have implications for understanding enzyme evolution and suggest that selectively targeting the conformational dynamics of the transition-state ensemble by design and evolution will expedite the creation of novel enzymes.

Controlling the assembly and disassembly of nanoscale protein cages for the capture and internalization of protein or non-proteinaceous components is fundamentally important to a diverse range of bionanotechnological applications. Here, we study the reversible, pressure-induced dissociation of a natural protein nanocage, E. colibacterioferritin (Bfr), using synchrotron radiation small-angle X-ray scattering (SAXS) and circular dichroism (CD). We demonstrate that hydrostatic pressures of 450 MPa are sufficient to completely dissociate the Bfr 24-mer into protein dimers, and the reversibility and kinetics of the reassembly process can be controlled by selecting appropriate buffer conditions. We also demonstrate that the heme B prosthetic group present at the subunit dimer interface influences the stability and pressure lability of the cage, despite its location being discrete from the interdimer interface that is key to cage assembly. This indicates a major cage-stabilizing role for heme within this family of ferritins.

The ability to perform data assimilation in the Whole Atmosphere Community Climate Model eXtended version (WACCMX) is implemented using the Data Assimilation Research Testbed (DART) ensemble adjustment Kalman filter. Results are presented demonstrating that WACCMX+DART analysis fields reproduce the middle and upper atmosphere variability during the 2009 major sudden stratospheric warming (SSW) event. Compared to specified dynamics WACCMX, which constrains the meteorology by nudging toward an external reanalysis, the large‐scale dynamical variability of the stratosphere, mesosphere, and lower thermosphere is improved in WACCMX+DART. This leads to WACCMX+DART better representing the downward transport of chemical species from the mesosphere into the stratosphere following the SSW. WACCMX+DART also reproduces most aspects of the observed variability in ionosphere total electron content and equatorial vertical plasma drift during the SSW. Hindcast experiments initialized on 5, 10, 15, 20, and 25 January are used to assess the middle and upper atmosphere predictability in WACCMX+DART. A SSW, along with the associated middle and upper atmosphere variability, is initially predicted in the hindcast initialized on 15 January, which is ∼10 days prior to the warming. However, it is not until the hindcast initialized on 20 January that a major SSW is forecast to occur. The hindcast experiments reveal that dominant features of the total electron content can be forecasted ∼10–20 days in advance. This demonstrates that whole atmosphere models that properly account for variability in lower atmosphere forcing can potentially extend the ionosphere‐thermosphere forecast range. Whole atmosphere models offer the opportunity to improve specification and forecasting of the upper atmosphere through incorporating the effects of forcing from both the lower atmosphere as well as the Sun. This study presents initial results from a data assimilation version of the Whole Atmosphere Community Climate Model eXtended version (WACCMX+DART). WACCMX extends from the surface to ∼500 km altitude and thus simultaneously models the lower, middle, and upper atmospheres. By assimilating meteorological observations in the troposphere‐stratosphere, and satellite observations in the mesosphere, WACCMX+DART reanalysis fields are shown to reproduce the ionosphere variability during the 2009 sudden stratospheric warming (SSW) event. The ionosphere predictability during the 2009 SSW event is also assessed through a series of hindcast experiments that are initialized approximately 20, 15, 10, 5, and 0 days prior to the central (i.e., peak) date of the SSW. The hindcast experiments reveal that for the 2009 SSW event, the middle and upper atmosphere variability can be qualitatively forecasted 10–20 days in advance. The results demonstrate that it is possible to extend the useful forecast range of the ionosphere‐thermosphere through incorporating lower atmosphere effects, at least during periods of quiescent solar activity. This study presents initial results of a whole atmosphere‐ionosphere data assimilation model, WACCMX+DARTMiddle and upper atmosphere variability is well reproduced in WACCMX+DART analysis fieldsSSW and associated middle and upper atmosphere variability can be forecast ∼10 days in advance

Understanding changes in the burden and growth rate of atmospheric methane (CH4) has been the focus of several recent studies but still lacks scientific consensus. Here we investigate the role of decreasing anthropogenic carbon monoxide (CO) emissions since 2002 on hydroxyl radical (OH) sinks and tropospheric CH4loss. We quantify this impact by contrasting two model simulations for 2002–2013: (1) a Measurement of the Pollution in the Troposphere (MOPITT) CO reanalysis and (2) a Control‐Run without CO assimilation. These simulations are performed with the Community Atmosphere Model with Chemistry of the Community Earth System Model fully coupled chemistry climate model with prescribed CH4surface concentrations. The assimilation of MOPITT observations constrains the global CO burden, which significantly decreased over this period by ~20%. We find that this decrease results to (a) increase in CO chemical production, (b) higher CH4oxidation by OH, and (c) ~8% shorter CH4lifetime. We elucidate this coupling by a surrogate mechanism for CO‐OH‐CH4that is quantified from the full chemistry simulations. Decreases in tropospheric CO from 2002 to 2012 indicate an increase in CH4chemical lossThere is a positive trend in the chemical production of CO from CH4in the tropicsWe infer a reduced growth rate in CH4burden due to decreases in anthropogenic CO emissions

The transition from late‐orogenic to post‐orogenic magmatism following major orogenic episodes such as the Neoproterozoic to Cambrian East African Orogen (EAO) is an important, yet not well‐understood geological event marking the cessation of subduction‐controlled magmatism between buoyant lithospheric fragments. Forming the northern part of the EAO in the Arabian‐Nubian Shield are three granitic suites that successively intruded the same northeastern area and post‐date the ~640 Ma major orogenic episode: (1) 620–600 Ma alkali feldspar (hypersolvous) granite with alkaline/ferroan/A‐type geochemistry, (2) 599 Ma granite cumulates (some garnet‐bearing) with calc‐alkaline/magnesian affinities, and (3) 584–566 Ma alkali feldspar (hypersolvous) granite (aegirine‐bearing) with a distinctive peralkaline/ferroan/A‐type signature. Combining whole‐rock geochemistry from the southern and northern Arabian Shield, suites 1 and 2 are suggested to be products of late‐orogenic slab tear/rollback inducing asthenospheric mantle injection and lower crustal melting/fractionation toward A‐type/ferroan geochemistry. Suite 3, however, is suggested to be produced by post‐orogenic lithospheric delamination, which replaced the older mantle with new asthenospheric (rare earth element‐enriched) mantle that ultimately becomes the thermal boundary layer of the new lithosphere. Major shear zones, such as the 620–540 Ma Najd Fault System (NFS), are some of the last tectonic events recorded across the Arabian Shield. Data presented here suggest that the NFS is directly related to the late‐orogenic (620–600 Ma) slab tear/rollback in the northeastern Shield as it met with opposing subduction polarity in the southern Shield. Furthermore, this study infers that east and west Gondwana amalgamation interacted with opposing convergence reflected by the NFS. Three granites from the NE Arabian Shield post‐date a ~640 Ma major orogenic episode and record a change in mantle sourceGeochemical comparison suggests late‐orogenic lower crustal melting induced by slab tear followed by a switch to lithospheric delaminationLate‐orogenic magmatism symbolizes an extensional phase of a major transpressional shear zone generated by opposing subduction polarity

Galectin-1 (Gal-1) is involved in tumoral angiogenesis, hypoxia and metastases. Actually the Gal-1 expression profile in multiple myeloma (MM) patients and its pathophysiological role in MM-induced angiogenesis and tumoral growth are unknown. In this study, we found that Gal-1 expression by MM cells was upregulated in hypoxic conditions and that stable knockdown of hypoxia inducible factor-1a significantly downregulated its expression. Therefore, we performed Gal-1 inhibition using lentivirus transfection of shRNA anti-Gal-1 in human myeloma cell lines (HMCLs), and showed that its suppression modified transcriptional profiles in both hypoxic and normoxic conditions. Interestingly, Gal-1 inhibition in MM cells downregulated proangiogenic genes, including MMP9and CCL2, and upregulated the antiangiogenic ones SEMA3Aand CXCL10. Consistently, Gal-1 suppression in MM cells significantly decreased their proangiogenic properties in vitro. This was confirmed in vivo, in two different mouse models injected with HMCLs transfected with anti-Gal-1 shRNA or the control vector. Gal-1 suppression in both models significantly reduced tumor burden and microvascular density as compared with the control mice. Moreover, Gal-1 suppression induced smaller lytic lesions on X-ray in the intratibial model. Overall, our data indicate that Gal-1 is a new potential therapeutic target in MM blocking angiogenesis.

The intraseasonal variability of the eastward propagating nonmigrating diurnal tide with zonal wave number 3 (DE3) during 2007 in the mesosphere, ionosphere, and thermosphere is investigated using a whole atmosphere model reanalysis and satellite observations. The atmospheric reanalysis is based on implementation of data assimilation in the Whole Atmosphere Community Climate Model (WACCM) using the Data Assimilation Research Testbed (DART) ensemble Kalman filter. The tidal variability in the WACCM+DART reanalysis is compared to the observed variability in the mesosphere and lower thermosphere (MLT) based on the Thermosphere Ionosphere Mesosphere Energetics Dynamics satellite Sounding of the Atmosphere using Broadband Emission Radiometry (TIMED/SABER) observations, in the ionosphere based on Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) observations, and in the upper thermosphere (∼475 km) based on Gravity Recovery and Climate Experiment (GRACE) neutral density observations. To obtain the short‐term DE3 variability in the MLT and upper thermosphere, we apply the method of tidal deconvolution to the TIMED/SABER observations and consider the difference in the ascending and descending longitudinal wave number 4 structure in the GRACE observations. The results reveal that tidal amplitude changes of 5–10 K regularly occur on short timescales (∼10–20 days) in the MLT. Similar variability occurs in the WACCM+DART reanalysis and TIMED/SABER observations, demonstrating that the short‐term variability can be captured in whole atmosphere models that employ data assimilation and in observations by the technique of tidal deconvolution. The impact of the short‐term DE3 variability in the MLT on the ionosphere and thermosphere is also clearly evident in the COSMIC and GRACE observations. Analysis of the troposphere forcing in WACCM+DART and simulations of the Global Scale Wave Model (GSWM) show that the short‐term DE3 variability in the MLT is not related to a single source; rather, it is due to a combination of changes in troposphere forcing, zonal mean atmosphere, and wave‐wave interactions. Short‐term DE3 variability in observations is compared with WACCM+DART reanalysisShort‐term variability found to occur in MLT, ionosphere, and upper thermosphereSeveral different mechanisms combine to generate the short‐term variability

We reported that p62 (sequestosome 1) serves as a signaling hub in bone marrow stromal cells (BMSCs) for the formation of signaling complexes, including NF?B, p38MAPK and JNK, that are involved in the increased osteoclastogenesis and multiple myeloma (MM) cell growth induced by BMSCs that are key contributors to multiple myeloma bone disease (MMBD), and demonstrated that the ZZ domain of p62 (p62-ZZ) is required for BMSC enhancement of MMBD. We recently identified a novel p62-ZZ inhibitor, XRK3F2, which inhibits MM cell growth and BMSC growth enhancement of human MM cells. In the current study, we evaluate the relative specificity of XRK3F2 for p62-ZZ, characterize XRK3F2’s capacity to inhibit growth of primary MM cells and human MM cell lines, and test the in vivoeffects of XRK3F2 in the immunocompetent 5TGM1 MM model. We found that XRK3F2 induces dramatic cortical bone formation that is restricted to MM containing bones and blocked the effects and upregulation of tumor necrosis factor alpha (TNFa), an osteoblast (OB) differentiation inhibitor that is increased in the MM bone marrow microenvironment and utilizes signaling complexes formed on p62-ZZ, in BMSC. Interestingly, XRK3F2 had no effect on non-MM bearing bone. These results demonstrate that targeting p62 in MM models has profound effects on MMBD.

Introduction: Female flight attendants may have a higher risk of breast and other cancers than the general population because of routine exposure to cosmic radiation. As part of a forthcoming study of breast and other cancer incidence, occupational cosmic radiation exposure of a cohort of female flight attendants was estimated. Methods: Questionnaire data were collected from living female cohort members who were formerly employed as flight attendants with Pan American World Airways. These data included airline at which the flight attendant was employed, assigned domicile, start and end dates for employment at domicile, and number of block hours and commuter segments flown per month. Questionnaire respondents were assigned daily absorbed and effective doses using a time-weighted dose rate specific to the domicile and/or work history era combined with self-reported work history information. Results: Completed work history questionnaires were received from 5898 living cohort members. Mean employment time as a flight attendant was 7.4 yr at Pan Am and 12 yr in total. Estimated mean annual effective dose from all sources of occupational cosmic radiation exposure was 2.5 ± 1.0 mSv, with a mean career dose of 30 mSv. Discussion: Annual effective doses were similar to doses assessed for other flight attendant cohorts; however, questionnaire-based cumulative doses assessed in this study were on average higher than those assessed for other flight attendant cohorts using company-based records. The difference is attributed to the inclusion of dose from work at other airlines and commuter flights, which was made possible by using questionnaire data. [ABSTRACT FROM AUTHOR]

The objective of this experiment was to determine the effect that the amount of condensed distillers solubles (CDS) added back to distillers grains (DG) and its form, wet or dried, have on nutrient digestion. Three Holstein cows with ruminal cannulas were used to evaluate in situ ruminal degradability of DM and CP and in vitro intestinal digestibility of CP. Condensed distillers solubles were added back to wet DG in the following ratios of wet DG to CDS: 100:0, 86.7:13.3, 73.3:26.7, and 60:40. One-half of each mixed feed at each ratio was dried, and the other one-half remained wet, resulting in 8 DG samples. Feeds were incubated in the rumen for 0, 3, 6, 12, 18, 24, and 48 h. Intestinal CP digestibility was measured on residue from 12-h ruminal incubation feeds by the pepsin-pancreatin method. The soluble fraction of DM and CP was greater (P< 0.001) for wet compared with dried DG and increased as CDS increased in each blend (P< 0.001). The potentially degradable fraction of DM and CP was greater (P< 0.001) for dried compared with wet DG and decreased as CDS increased in each blend (P< 0.01). The rate of DM and CP degradation was not (P> 0.05) affected by form or inclusion of CDS. Rumen-degraded DM was greater (P< 0.001) for wet compared with dried DG (59.7 vs. 48.6%), and as the percentage of CDS increased, it increased (P< 0.001) from 49.3 to 61.2%. Rumen-degraded protein (RDP) was greater (P< 0.001) for wet DG than dried DG (53.1 vs. 38.0%). In addition, RDP increased (P< 0.001) from 42.0 to 50.5% as the concentration of CDS increased from 0 to 40%. Estimated intestinal digestibility of rumen-undegraded protein was greater (P= 0.003) for wet DG compared with dried DG (69.7 vs. 64.0%), but was unaffected (P= 0.11) by the addition of CDS. Intestinal absorbable dietary protein was greater (P< 0.001) for dried DG (39.7%) compared with wet DG (32.7%), and decreased (P< 0.001) from 39.9 to 32.0% with increasing concentrations of CDS. Total digestible protein (TDP) increased (P< 0.001) from 77.7 to 85.8% for dried and wet DG, whereas different ratios of DG to CDS resulted in similar TDP. Based on this study, ruminal DM and CP degradability and intestinal protein digestibility of DG increased when the percentage of CDS increased. Although dried DG can supply more ruminal undegraded protein, wet DG can supply more TDP.

Two experiments were conducted to evaluate the fermentation characteristics of ensiled wet corn distillers grains with solubles (WDG) alone or mixed with soybean hulls (SH) and the ability of the mixture to maintain growth performance in dairy heifers. The first experiment was an ensiling study using laboratory silos. Ensiled blends were 100% WDG, 85% WDG with 15% SH, and 70% WDG with 30% SH on an as-fed basis. Silos were opened for analysis on d 0, 3, 7, and 21. The pH was less in the 100% WDG compared with other treatments (P< 0.01), but all treatments had a pH near 4. Lactic acid concentration was greater in 100% WDG compared with the blends of WDG and SH (P< 0.01). Acetic acid was not found in 100% WDG and increased over time in the 2 blends (P< 0.01). Other differences between blends, such as DM, CP, ammonia N, fiber, and fat, were reflective of the different concentrations of WDG and SH in the blends. In the second experiment, the 70% WDG and 30% SH (as-fed) blend was ensiled in a silo bag and then evaluated as a feed for growing dairy heifer diets. Twenty-four heifers were used in a randomized complete block design and assigned to be fed 1 of 3 diets: 1) control, 2) low inclusion of WDGSH, and 3) a high inclusion of WDGSH. All treatment diets consisted of 50% brome grass hay on a DM basis. The control diet had 50% of the diet (DM basis) as a grain mix, which was composed of corn, soybean meal, and minerals. The low WDGSH diet contained 24.4% of the blend and 25.6% grain mix. The high WDGSH diet contained 48.7% of the blend and 1.3% mineral mix. Average daily gain and most of the body growth measures were similar among treatments. However, DMI decreased linearly (P< 0.01) as the WDGSH blends were fed, resulting in improved (P= 0.02) G:F. Results from these experiments indicated that WDG can be effectively ensiled with SH and sustain adequate growth rate when fed to growing dairy heifers.

We characterize the movement of carbon black particles in inhomogeneous, two-dimensional dc electric fields. Motivated by display applications, the particles are suspended in a nonpolar solvent doped with a charge control agent. The two-dimensional fields are generated between strip electrodes on a glass slide spaced 120 μm apart with field strengths up to 10⁴ V/m. Such fields are insufficient to drive either electrohydrodynamic instabilities or natural convection due to ohmic heating, but they move the particles between the electrodes in about 30 s. In the center region between the strip electrodes, the particles move by electrophoresis; that is, the particle velocity is proportional to the electric field. However, when imposing a constant-potential or constant-current boundary condition at the electrodes to derive the electrical field, the electrophoretic mobility calculated from the measured particle velocities is outside the range of mobilities predicted from the theory of O'Brien and White. Near the electrodes the particles either speed up or slow down, depending on the polarity of the electrode, and these changes in velocity cannot be explained simply by electrophoresis in a spatially varying electric field. We suggest that this anomalous motion arises from electrohydrodynamic flows originating from the interaction between the space charge of the polarized layers above the electrodes and the electric field. Approximate calculations indicate such flows could be sufficiently strong to explain the anomalous trajectories near the edges of the electrodes.

A series of novel aminoalkylindoles was synthesized in an effort to develop compounds that are potent agonists at the CB1 cannabinoid receptor and that are also easily labeled with radioisotopes of iodine for biochemical and imaging studies. 2-Iodophenyl-[1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl]methanone (8, AM2233) had a very high affinity for the rat CB1 receptor, with most of the affinity residing with the (R)-enantiomer. Radioiodinated 8, (R)-8, and (S)-8 were prepared by radioiododestannylation of the tributyltin analogues in high yields, radiochemical purities, and specific radioactivities. In a mouse hippocampal membrane preparation with [¹³¹I](R)-8 as radioligand, racemic 8 exhibited a Ki value of 0.2 nM compared with 1.6 nM for WIN55212-2. In autoradiographic experiments with mouse brain sections, the distribution of radioiodinated 8 was consistent with that of brain CB1 receptors. Again, very little specific binding was seen with the (S)-enantiomer [¹³¹I](S)-8 and none occurred with the (R)-enantiomer [¹³¹I](R)-8 in sections from CB1 receptor knockout mice. Radioiodinated 8 thus appears to be a suitable radioligand for studies of CB1 cannabinoid receptors.

Electrical current versus potential relationships were measured for solutions of dodecane containing the charge control agent poly(isobutylene succinimide) (PIBS) at various concentrations. Both one-dimensional (parallel planar electrodes) and two-dimensional (strip electrodes) fields were studied. The initial current was proportional to the applied voltage for both electrode configurations. Using the initial decay rate of the current (t &lt; 0.5 s) in the planar electrode cell and the Gouy−Chapman model for electrode polarization, we determined the diffusion coefficient of the charge carriers (micelles) in the solution, from which we calculated their effective radius to be 10 nm. The constancy of the carrier radius over a 7-fold change in PIBS concentration, along with the proportionality between conductivity and concentration, supports the hypothesis that the charged species result from the interactions between two micelles. The experimentally determined geometric factor (cell constant) relating current to applied potential at time zero for the strip electrode cell agrees with the value predicted from the solution of Laplace's equation for the electrical potential in this system. The intermediate-time (0.5−3.0 s) decay rate of current was faster than predicted from the classical Gouy−Chapman theory of the double layer, possibly because of volume fraction effects in the double layer. The very long-time (minutes to hours) residual current that we observed is not explained, but we suspect that some charge transfer across the electrode must have occurred because there was insufficient ion capacity (i.e., amount of PIBS) in the solution to account for the total charge transferred through the cell.

AbstractThe atomic structure of synthetic, deuterated goslarite (ZnSO4·7D2O), a= 11.8176(6) Å, b= 12.0755(7) Å, c= 6.8270(4)Å, space group P212121, Z= 4, has been refined in a combined neutron powder diffraction and X-ray single-crystal data refinement to wRp1.92%, Rp1.45% and R(F2)12.66% for the neutron powder data contribution and R(F2) 8.72% for the X-ray single-crystal data contribution. Both data sets were necessary to achieve the best overall fit agreement in the Rietveld refinement and reasonable geometry within structural units. The results of this study confirm that the H-bonding scheme for goslarite is the same as that of the other epsomite group minerals. Small but significant variations of the Zn–O bond lengths can be attributed to details of the H bonds to the O atoms of the Zn octahedra. This investigation of the atomic structure and hydrogen bonding of goslarite is groundwork for future studies into phase relationships and the mechanisms of hydration and dehydration in the ZnSO4–H2O system.

We have designed, synthesized, and characterized a metal chelating compound that is based on the structure of cholesterol and contains the high affinity metal chelating group, lysine nitrilotriacetic acid (Lys-NTA). Using the enzyme isoprenylcysteine carboxylmethyltransferase (Icmt) from yeast as a model integral membrane metalloenzyme, we find that this agent potently inhibits Icmt activity with an IC50 value between 35 and 75 μM, which is at least 40 times more potent than the best known Icmt metal chelating inhibitor, Zincon. We propose that the rigid hydrophobic cholesterol moiety promotes partitioning into the membrane, enabling the metal-binding NTA group(s) to inactivate the enzyme by metal chelation. Because this compound is based on a naturally occurring membrane lipid and appears to chelate metals buried deeply within water insoluble environments, this agent may also be useful as a general tool for identifying previously unappreciated metal dependencies of other classes of membrane proteins.

The genus Halosarpheia(Halosphaeriales) was established for marine ascomycetes with obpyriform to sub-globose, coriaceous, brown to black ostiolate ascomata with long necks; hamathecia of catenophyses; thin-walled, unitunicate, persistent asci with thick-walled apices; and ellipsoid, one septate, hyaline ascospores equipped with coiled, threadlike apical appendages that unfurl in water. Emphasis on ascospore appendage morphology has led to the inclusion in the genus of morphologically disparate fungi from a variety of marine and freshwater habitats. To better understand the evolutionary relationships of Halosarpheiaspecies, phylogenetic analyses were conducted on 16 Halosarpheiaspecies, 13 other species of Halosphaeriales and representatives of the Microascales, Hypocreales, Sordariales and Xylariales using 18S and 28S rDNA sequence data. All of the Halosarpheiaspecies occurred on the Halosphaeriales clade. The type species of the genus, H. fibrosa, occurred on a well-supported clade with two morphologically similar species, H. trulliferaand H. unicellularis. This clade, which phylogenetically was distant from the clades of other Halosarpheiaspecies, represents the genus Halosarpheiasensu stricto. The other Halosarpheiaspecies were distributed among eight other well-supported clades clearly separated from one another based on molecular data. New generic names are established for six of these clades, one new species is described, and one species is transferred to Aniptodera. A table (Table I) comparing the morphology, habitat, substrate and distribution of the genera of aquatic ascomycetes with coiled, threadlike apical appendages treated in this study is provided, along with a key for their identification.

In our efforts toward developing a nonselective ligand that would block the effects of stimulants such as methamphetamine at dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporters, we synthesized a series of 3-(3,4-dichlorophenyl)-1-indanamine derivatives. Two of the examined higher affinity compounds had a phenolic hydroxyl group enabling preparation of a medium to long chain carboxylic acid ester that might eventually be useful for a long-acting depot formulation. The in vitro data indicated that (−)-(1R,3S)-trans-3-(3,4-dichlorophenyl)-6-hydroxy-N-methyl-1-indanamine ((−)-(1R,3S)-11) displays high-affinity binding and potent inhibition of uptake at all three biogenic amine transporters. In vivo microdialysis experiments demonstrated that intravenous administration of (−)-(1R,3S)-11 to rats elevated extracellular DA and 5-HT in the nucleus accumbens in a dose-dependent manner. Pretreating rats with 0.5 mg/kg (−)-(1R,3S)-11 elevated extracellular DA and 5-HT by approximately 150% and reduced methamphetamine-induced neurotransmitter release by about 50%. Ex vivo autoradiography, however, demonstrated that iv administration of (−)-(1R,3S)-11 produced a dose-dependent, persistent occupation of 5-HT transporter binding sites but not DA transporter sites.

Heme-containing proteins are one of the most structurally and functionally diverse groups of proteins in nature. Central to our understanding of their function is an appreciation of the fundamental inorganic and physical properties of the heme prosthetic group itself. Many spectroscopic techniques have been used to probe heme proteins but these alone often cannot reveal all of the key information required. Many exogeneous heme-iron ligands have been shown to be highly sensitive to the electronic and physical properties of protein-bound heme groups. Such ligands, used in combination with spectroscopic andor crystallographic analyses, have proved to be particularly useful in probing not only the heme prosthetic group itself but also the surrounding structure and dynamics of the protein active-site. In this perspective, we introduce five diverse families of heme-proteins and discuss how the use of heme-coordinating ligands has provided immensely important information about the physical and structural properties of each heme-protein family.

The crystal structures of three analogues of the potent δ-opioid receptor antagonist H-Dmt-Tic-OH (2‘,6‘-dimethyl-l-tyrosine-l-1,2,3,4-tetrahydroisoquinoline-3-carboxylate), N,N (CH3)2-Dmt-Tic-OH (1), H-Dmt-Tic-NH-1-adamantane (2), and N,N(CH3)2-Dmt-Tic-NH-1-adamantane (3) were determined by X-ray single-crystal analysis. Crystals of 1 were grown by slow evaporation, while those of 2 and 3 were grown by vapor diffusion. Compounds 1 and 3 crystallized in the monoclinic space group P21, and 2 crystallized in the tetragonal space group P43. Common backbone atom superimpositions of structures derived from X-ray diffraction studies resulted in root-mean-square (rms) deviations of 0.2−0.5 Å, while all-atom superimpositions gave higher rms deviations from 0.8 to 1.2 Å. Intramolecular distances between the aromatic ring centers of Dmt and Tic were 5.1 Å in 1, 6.3 Å in 2, and 6.5 Å in 3. The orientation of the C-terminal substituent 1-adamantane in 2 and 3 was affected by differences in the ψ torsion angles and strong hydrogen bonds with adjacent molecules. Despite the high δ-opioid receptor affinity exhibited by each analogue (Ki &lt; 0.3 nM), high μ-receptor affinity (Ki &lt; 1 nM) was manifested only with the bulky C-terminal 1-adamantane analogues 2 and 3. Furthermore, the bioactivity of both 2 and 3 exhibited μ-agonism, while 3 also had potent δ-antagonist activity. Those data demonstrated that a C-terminal hydrophobic group was an important determinant for eliciting μ-agonism, whereas N-methylation maintained δ-antagonism. Furthermore, the structural results support the hypothesis that expanded dimensions between aromatic nuclei is important for acquiring μ-agonism.

The relative motion between two colloidal particles loosely deposited on an electrode passing alternating current was investigated. Parameters such as zeta potential, electrolyte composition, electrolyte concentration, and frequency were varied. At a low frequency (100 Hz), the particles aggregated in both sodium bicarbonate and sodium chloride solutions but separated in sodium hydroxide solutions. At 1000 Hz, the particles separated in both bicarbonate and hydroxide solutions, and the rate of separation was slower than at 100 Hz for the hydroxide solutions. The effect of zeta potential was negligible, indicating a convective mechanism causing the relative motion between the particles. Electrolyte concentration had no appreciable effect on the motion. These results are qualitatively consistent with predictions of a theory based on electrohydrodynamic flow induced by the interaction between a space charge in the liquid adjacent to the electrode's surface, generated by concentration gradients of the ions, and an electric field tangent to the electrode which is caused by deflection of current around each particle. The interparticle separation velocity in hydroxide solutions predicted from the theory without adjustable parameters is comparable to the experimental values.

The hydrodynamic (solvent) permeability of porous membranes filled with cross-linked polyacrylamide (PA) was measured as a function of pore size, surface chemistry, and solvent quality. The gel was formed by first soaking the membrane in the solution containing the acrylamide monomer, cross-linking agent, and initiator, and then polymerizing in situ using thermal activation. The water permeability of the gel-filled membranes at a fixed polymer volume fraction within the pores was insensitive to the pore diameter over the range 0.09−0.48 μm. There was no measurable effect of two different surface chemistries, indicating that the gel was trapped inside the porous matrix rather than covalently bonded to the internal membrane surfaces. The most important result was that there were large variations of the permeability when the quality of the solvent was made poorer by adding different alcohols to water. Going from a good solvent for PA (water) to poorer solvents (increasing alcohol concentration), the permeability increased. For example, the hydrodynamic permeability of the membrane-supported gels increased 100 times at alcohol concentrations for which bulk gel collapsed by a factor of 7 in volume. The large changes in permeability of the membrane-supported gels were reversible when the alcohol content of the solvent was reduced; the gel's permeability in pure water was always recovered to within ±15% after exposing the gel to alcohol-rich solutions. These results, along with results of partitioning and filtration experiments using colloidal particles, support the conjecture that a membrane-supported gel undergoes microsyneresis (coarsening of the microstructure) when exposed to a poor solvent but does not collapse as a bulk gel would.

Duchenne muscular dystrophy (DMD) is the second most commonly occurring genetically inherited disease in humans. It is an X-linked condition that affects approximately one in 3300 live male births. It is caused by the absence or disruption of the protein dystrophin, which is found in a variety of tissues, most notably skeletal muscle and neurones in particular regions of the CNS. Clinically DMD is characterized by a severe pathology of the skeletal musculature that results in the premature death of the individual. An important aspect of DMD that has received less attention is the role played by the absence or disruption of dystrophin on CNS function. In this review we concentrate on insights into this role gained from investigation of boys with DMD and the genetically most relevant animal model of DMD, the dystrophin-deficient mdx mouse. Behavioural studies have shown that DMD boys have a cognitive impairment and a lower IQ (average 85), whilst the mdx mice display an impairment in passive avoidance reflex and in short-term memory. In DMD boys, there is evidence of disordered CNS architecture, abnormalities in dendrites and loss of neurones, all associated with neurones that normally express dystrophin. In the mdx mouse, there have been reports of a 50% decrease in neurone number and neural shrinkage in regions of the cerebral cortex and brainstem. Histological evidence shows that the density of GABA(A) channel clusters is reduced in mdx Purkinje cells and hippocampal CA1 neurones. At the biochemical level, in DMD boys the bioenergetics of the CNS is abnormal and there is an increase in the levels of choline-containing compounds, indicative of CNS pathology. The mdx mice also display abnormal bioenergetics, with an increased level of inorganic phosphate and increased levels of choline-containing compounds. Functionally, DMD boys have EEG abnormalities and there is some preliminary evidence that synaptic function is affected adversely by the absence of dystrophin. Electrophysiological studies of mdx mice have shown that hippocampal neurones have an increased susceptibility to hypoxia. These recent findings on the role of dystrophin in the CNS have implications for the clinical management of boys with DMD.

We have prepared azabicyclo[3.2.1] derivatives (C-3-substituted tropanes) that bind with high affinity to the dopamine transporter and inhibit dopamine reuptake. Within the series, 3-{2-[bis-(4-fluorophenyl)methoxy]ethylidene}-8-methyl-8-azabicyclo[3.2.1]octane (8) was found to have the highest affinity and selectivity for the dopamine transporter. These azabicyclo[3.2.1] (bridged piperidine) series of compounds differ from the well-known benztropines by a 2-carbon spacer between C-3 and a diarylmethoxy moiety. Interestingly, these new compounds demonstrated a much lower affinity for the muscarinic-1 site, at least a 100-fold decrease compared to benztropine. Replacing N-methyl with N-phenylpropyl in two of the compounds resulted in a 3−10-fold increase in binding affinity for the dopamine transporter. However, those compounds lost selectivity for the dopamine transporter over the serotonin transporter. Replacement of the ether oxygen in the diarylmethoxy moiety with a nitrogen atom gave relatively inactive amines, indicating the important role which is played by the ether oxygen in transporter binding. Reduction of the C-3 double bond in 8 gave 3α-substituted tropanes, as shown by X-ray crystallographic analyses of 11, 12, and 19. The 3α-substituted tropanes had lower affinity and less selectivity than the comparable unsaturated ligands.

With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the phenyl group of the phenylcarbamoyl moieties, and with N-methyl and 6-methyl substituents (12, 13, 31, 33). We also quantified the inhibitory action of these compounds against human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). An analysis of the structure/anticholinesterase activity relationship of the described compounds, together with molecular modeling, confirmed the catalytic triad mechanism of the binding of this class of carabamate analogues within AChE and BChE and defined structural requirements for their differential inhibition.

AbstractSpecies of Halosarpheia, a genus of aquatic Ascomycetes, are morphologically unified by the presence of unfurling ascospore appendages. This character state may be unreliable for resolving evolutionary relationships, however, due to its likely adaptive nature. Taxonomic emphasis on unfurling ascospore appendages has led to the inclusion of species within Halosarpheiathat are morphologically similar enough to confound identification, as well as those distinct enough to question their placement in the genus. Phylogenetic analyses of 18S rDNA sequences demonstrate polyphyly of the genus, with H. fibrosa, the type of the genus, resolved separately from all other species of Halosarpheiaanalyzed. Morphologically similar species H. retorquens, H. viscosa, H. heteroguttulata, and H. loticaare distinct species separable by RFLP analysis of the ITS1 region as well as 18S rDNA sequence analyses. Some morphological characters used to delineate species within Halosarpheia, such as ascospore guttulation pattern and number of ascospore appendages, may actually reflect generic differences that have been overshadowed by convergent evolution in appendage type.

Novel piperidine-based bivalent ligands were prepared in enantiomerically pure form and evaluated for their ability to inhibit reuptake of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) into rat brain nerve endings (synaptosomes). In this study, we have succeeded in using (1) the length of the linking chain connecting the two piperidine-based monomer units and (2) the absolute configuration of the piperidine monomer as a means to tailor activity and selectivity at the three monoamine transporters tested. In this series, the bivalent ligand 16, comprised of two (+)-trans-piperidine units linked by a pentamethylene spacer, exhibits a combination of high DA transporter (DAT) and 5-HT transporter (SERT) activity (Ki = 39 nM and 7 nM, respectively). Piperidine 16 is capable of reducing cocaine's locomotor effects in mice while not having any effect on locomotion when tested alone. Additionally, compound 16 (1−10 mg/kg) does not substitute for cocaine in drug discrimination studies in rats. However, the analogous bivalent ligand 15 comprised of two (−)-trans-piperidine units, which is SERT selective, was less effective in antagonizing cocaine's locomotor stimulant activity. The piperidine-based bivalent inhibitors described herein constitute a new class of monoamine reuptake inhibitors that exhibit varying levels of monoamine transporter activity and selectivity, and these ligands may serve as lead candidates in the discovery of new therapeutics to treat a range of neurological disorders including cocaine addiction.

A study of the effect of transposition of the internal nitrogen atom for the adjacent benzylic carbon atom in δ-selective agonists such as BW373U86 (1) and SNC-80 (2) has been undertaken. It was shown that high-affinity, fully efficacious, and δ opioid receptor-selective compounds can be obtained from this transposition. In addition to the N,N-diethylamido group needed as the δ address, the structural features identified to promote δ receptor affinity in the set of compounds studied included a cis relative stereochemistry between the 3- and 4-substituents in the piperidine ring, a trans-crotyl or allyl substituent on the basic nitrogen, the lack of a 2-methyl group in the piperidine ring, and either no substitution or hydroxyl substitution in the aryl ring not substituted with the N,N-diethylamido group. Structural features found to be important for μ affinity include hydroxyl substitution in the aryl ring, the presence of a 2-methyl group in a cis relative relationship to the 4-amino group as well as N-substituents such as cyclopropylmethyl. It was also determined that μ receptor affinity could be increased while maintaining δ receptor affinity, especially when hydroxyl-substituted compounds are considered. Additionally, it was discovered that the somewhat lower μ/δ selectivities observed for the piperidine compounds relative to the piperazine-based ligands appear to arise as a consequence of the carbon−nitrogen transposition which imparts an overall lower δ and higher μ affinity to the piperidine-based ligands. This higher affinity for the μ receptor, apparently intrinsic to the piperidine-based compounds, suggests that ligands of this class will more easily be converted to μ/δ combination agonists compared to the piperazine ligands such as 1. This is particularly important since analogues of 1, which show both μ- and δ-type activity, are now recognized as important for their strong analgesia and cross-canceling of many of the side effects found in agonists operating exclusively from either the δ or μ opioid receptor.

Today there are many choices for a community faced with the need to upgrade its failing sewage treatment system. The objective of this case is to teach participants how to weigh choices that affect the whole community by involving them in a decision of wastewater treatment in a small rural town. Current alternative wastewater systems as well as traditional systems should be considered. The dilemma is to choose a system that will be efficient, affordable for the citizens of the community, and ultimately avoid surface and ground water pollution. Once a system has been chosen, it must follow a management plan to be effective over time. The decision involves not only the citizens of the town, but the city engineer and other state and county agencies concerned with the environmental and human health hazards caused by inadequate wastewater treatment.

A series of methoxy-containing derivatives of indatraline 13a−f and 17 were synthesized, and their binding affinities for the dopamine, serotonin, and norepinephrine transporter binding sites were determined. Introduction of a methoxy group to indatraline affected its affinity and selectivity greatly. Except for the 4-methoxy derivative 13a,which had the same high affinity at the dopamine transporter binding site as indatraline, the other methoxy-containing analogues (13b−f and 17) exhibited lower affinity than indatraline for the three transporter binding sites. However, some of the analogues were more selective than indatraline, and the 6-methoxy derivative 13c displayed the highest affinity for both the serotonin and norepinephrine transporters. This compound retained reasonable affinity for the dopamine transporter and is a promising template for the development of a long-acting inhibitor of monoamine transporters. Such inhibitors have potential as medications for treatment, as a substitution medication, or for prevention of the abuse of methamphetamine-like stimulants.

The motion of particles deposited on an electrode by electrophoresis is governed by electrokinetics, electrohydrodynamics, and Brownian diffusion. Under a dc electric field, the particles attract each other through their electroosmotic flows, but Brownian diffusion tends to randomize the distribution. Here, we develop a mathematical model for the time evolution of the probability of separation between two deposited particles. Predictions from the model for the mean separation versus time and the standard deviation about the mean separation are compared with experimental data for pairs of polystyrene latex particles deposited on thin-film metallic electrodes. The good agreement in the absence of adjustable parameters indicates that the convective−diffusion analysis based on electrokinetics is the mechanism behind particle aggregation during electrophoretic deposition under dc field conditions, that is, electroosmotic convection drives the particles together and the Brownian motion of the particles tends to separate them.

Differential electrophoresis is a technique for studying the forces holding two Brownian particles in a doublet configuration. The technique is based on the concept that particles having different zeta potentials (ζ) try to move at different velocities in an electric field but the colloidal forces holding the particles together frustrate the electrophoretic motion. A doublet with a dipole moment of ζ will rotate in an electric field; by measuring the angular velocity or stationary-state angular distribution, one is able to make conclusions about the rigidity of the doublet (i.e., whether or not there are forces acting tangentially to the surfaces of the two particles). At a sufficiently high electric field, the doublet aligns with the field and an electrophoretic displacement force tries to pull apart the doublet; this force, which is typically in the range 0.1−50 pN for micron size particles, can be calculated precisely from the electric field and known properties of the system. The doublet breaks if the electrophoretic displacement force exceeds the maximum attractive colloidal force. The electrophoretic rotation velocity and the displacement force are both proportional to the applied electric field and the difference in the ζ potentials between the two particles. Experimental results are reported for mixed doublets of a silica/polystyrene latex, which demonstrate the existence of tangential forces between the particles' surfaces and a time-dependent nature of the colloidal interactions.

The synthesis and monoamine transporter activity of additional members of a series of 3,4-disubstituted piperidines (truncated analogues of the WIN series) are described. All members of this series were prepared from arecoline hydrobromide in optically pure form and were evaluated for their ability to inhibit high affinity uptake of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) into rat brain nerve endings (synaptosomes). Most of the compounds prepared in this series are reasonably potent DAT inhibitors (Ki values of 4−400 nM) and have selectivity for the 5-HT transporter relative to both the NE transporter (3−9-fold) and to the DAT (≈25-fold). In the present series, (−)-methyl 1-methyl-4β-(2-naphthyl)piperidine-3β-carboxylate (6) was found to be the most potent piperidine-based ligand, exhibiting Ki's of 21 nM and 7.6 nM at the DAT and 5-HTT, respectively. While the 5-HTT activity of compound 6 is comparable to that of the antidepressant medication fluoxetine, it is less selective. As is apparent from the data presented, the naphthyl substituted piperidines 6−9, which differ in their stereochemistry, show different degrees of selectivity for the three transporters. Consistent with results reported in the literature for the tropane analogues, removal of the methyl group from the nitrogen atom of 9 leads to a further enhancement in 5-HTT activity. To examine the in vivo effects of these piperidines, preliminary behavioral screening was carried out on piperidine 14. Despite its 2.5-fold greater DAT activity compared to cocaine, piperidine 14 was found to be about 2.5-fold less potent in increasing distance traveled in mice. However, consistent with its DAT activity, piperidine 14 was found to be about 2.5-fold more potent than cocaine in enhancing stereotypic movements. Further studies of these piperidine-based ligands may provide valuable insights into the pharmacological mechanisms underlying the enhancement in distance traveled versus stereotypic movements. The present results have important implications for better understanding the structural motifs required in the design of agents with specific potency and selectivity at monoamine transporters.

The present study investigates the impact of assimilating electron density profiles from the Constellation Observing System for Meteorology, Ionosphere, and Climate‐2 (COSMIC‐2) mission in a whole atmosphere data assimilation system. The observations are assimilated into the Whole Atmosphere Community Climate Model with thermosphere‐ionosphere eXtension (WACCMX) using the Data Assimilation Research Testbed (DART) ensemble adjustment Kalman filter. Assimilation of the COSMIC‐2 electron density profiles during the evaluation time period of 25–30 April 2020 leads to improvement in both the 1 hr forecast and analysis electron densities in WACCMX + DART. Compared to a control experiment that does not assimilate COSMIC‐2 observations, the assimilation of the COSMIC‐2 electron density profiles reduces the 1 hr forecast root mean square error (RMSE) and bias with respect to COSMIC‐2 observations at 300 km by 6.76% and 24.91%, respectively. Assimilation of the COSMIC‐2 electron density profiles does not significantly influence the RMSE and bias with respect to ground‐based Global Navigation Satellite System vertical total electron content observations. The equatorial vertical plasma drift velocity in WACCMX + DART is changed by ±5–10 ms−1due to the assimilation of the COSMIC‐2 electron density profiles, indicating that the model representation of the electrodynamics of the low latitude ionosphere are significantly impacted by the assimilation of COSMIC‐2 observations. Assess the impact of assimilating Constellation Observing System for Meteorology, Ionosphere, and Climate‐2 (COSMIC‐2) electron density profiles in a whole atmosphere data assimilation systemAt 300 km, assimilating COSMIC‐2 electron densities reduces the 1 hr forecast root mean square error and bias by 6.76% and 24.91%Assimilating COSMIC‐2 electron densities leads to ±5–10 m/s changes in equatorial vertical plasma drift velocities Assess the impact of assimilating Constellation Observing System for Meteorology, Ionosphere, and Climate‐2 (COSMIC‐2) electron density profiles in a whole atmosphere data assimilation system At 300 km, assimilating COSMIC‐2 electron densities reduces the 1 hr forecast root mean square error and bias by 6.76% and 24.91% Assimilating COSMIC‐2 electron densities leads to ±5–10 m/s changes in equatorial vertical plasma drift velocities

The upward plasma drift and equatorial ionization anomaly (EIA) in the Earth's ionosphere are strongly influenced by the zonal electric field, which is generated by the wind dynamo. Specification and forecasting of thermospheric winds thus plays an important role in ionospheric weather prediction. In this study, we assess the impact of assimilating thermospheric wind observations from the Michelson Interferometer for Global High‐resolution Thermospheric Imaging (MIGHTI) instrument on NASA's Ionospheric CONnection (ICON) explorer satellite on the ionospheric electrodynamics. Empirical localization functions (ELFs) of ICON/MIGHTI zonal and meridional winds are also computed and applied to our data assimilation experiments, enabling improved assimilation of the ICON/MIGHTI wind observations. A set of observing system simulation experiments (OSSEs) are performed using the National Center for Atmospheric Research (NCAR) Whole Atmosphere Community Climate Model with thermosphere‐ionosphere eXtension (WACCMX) with data assimilation provided by the Data Assimilation Research Testbed (DART) ensemble adjustment Kalman filter. The results show that assimilating the ICON/MIGHTI wind observations with the ELF improves the zonal and meridional wind root mean square error (RMSE) by 16%–18% and 7%–10%, respectively. The improved wind specification further improves the low‐latitude E× Bvertical drift RMSE by about 18%. The response of electron densities is slower, and the overall impact is smaller. The improvement of the ionosphere F‐region maximum electron density (NmF2) between ±45° is about 8% after 18 days of data assimilation. ICON/MIGHTI meridional and zonal wind data are assimilated into the WACCMX + DART to adjust the thermospheric wind stateThe adjusted thermospheric wind state can further improve the predictability of the plasma drift by 18% and NmF2 by 8%Empirical localization functions are used to better assimilate the ICON/MIGHTI meridional and zonal wind observations ICON/MIGHTI meridional and zonal wind data are assimilated into the WACCMX + DART to adjust the thermospheric wind state The adjusted thermospheric wind state can further improve the predictability of the plasma drift by 18% and NmF2 by 8% Empirical localization functions are used to better assimilate the ICON/MIGHTI meridional and zonal wind observations

Therationaldesign, preparationandstructureassignmentof a rigid donor–spacer–acceptor system is simply achieved by the use of a strategy based on the synthesis of a peptide from conformationally restricted Cα‐tetrasubstituted α‐amino acids (see figure), and X‐ray diffraction and photophysical methods for crystal state and solution structure determination.