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We have measured the 30 and 100 eV far ultraviolet (FUV) emission cross sections of the optically allowed Fourth Positive Group (4PG) band system (A1Π → X1Σ+) of CO and the optically forbidden O (5So→ 3P) 135.6 nm atomic transition by electron‐impact‐induced‐fluorescence of CO and CO2. We present a model excitation cross section from threshold to high energy for the A1Π state, including cascade by electron impact on CO. The A1Π state is perturbed by triplet states leading to an extended FUV glow from electron excitation of CO. We derive a model FUV spectrum of the 4PG band system from dissociative excitation of CO2, an important process observed on Mars and Venus. Our unique experimental setup consists of a large vacuum chamber housing an electron gun system and the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission Imaging Ultraviolet Spectrograph optical engineering unit, operating in the FUV (110–170 nm). The determination of the total O i(5So) at 135.6 nm emission cross section is accomplished by measuring the cylindrical glow pattern of the metastable emission from electron impact by imaging the glow intensity about the electron beam from nominally zero to ~400 mm distance from the electron beam. The study of the glow pattern of O i(135.6 nm) from dissociative excitation of CO and CO2indicates that the O i(5So) state has a kinetic energy of ~1 eV by modeling the radial glow pattern with the published lifetime of 180 μs for the O i(5So) state. Both Mars and Venus have upper atmospheres that are similar in composition: mostly CO2, CO, and N2are dominant molecular gases, with nearly identical UV spectra. The modeling studies of atmospheric UV emissions cannot presently be accurately conducted to the same accuracy as the planetary UV measurements, which avail themselves with state‐of‐the‐art calibrated spectrographs. This dichotomy in accuracy between planetary observation and model occurs because the atomic and molecular emission cross sections with uncertainties of certain transitions are greater than 100%. Furthermore, the analysis is complicated by the spectral blending of the various emissions of the low‐resolution spectral spaceborne instruments. We present in this paper a UV laboratory instrument unique in the world at the University of Colorado that can measure for the first time the excitation mechanisms with accurate emission cross sections of both allowed and optically forbidden transitions that are occurring in a planetary atmosphere. We measured 30 and 100 eV emission cross sections of Fourth Positive band system of CO and O i(135.6 nm) from electron impact on CO and CO2We conducted a laboratory experiment measuring single‐scattering electron‐impact‐induced‐fluorescence FUV spectra from excitation of CO and CO2Fragment kinetic energy measurement for O i(5So) atoms found to be around ~1 eV from both CO and CO2molecular dissociation

We report the response of the Martian upper atmosphere to a strong X‐class flare on 10 September 2017 as observed by the Imaging Ultraviolet Spectrograph (IUVS) instrument aboard the Mars Atmosphere Volatile EvolutioN (MAVEN) mission. The solar flare peaked at 16:24 hr UT, and IUVS dayglow observations were taken about an hour after the flare peak. Retrieved temperatures from IUVS dayglow observations show a significant increase during the flare orbit, with a mean value of ∼270 K and a maximum value of ∼310 K. The retrieved temperatures during the flare orbit also show a strong latitudinal gradient, indicating that the flare‐induced heating is limited between low and middle latitudes. During this event IUVS observed an ∼70% increase in the observed brightness of CO 2+ultraviolet doublet and CO Cameron band emission at 90 km, where high‐energy photons (< 10 nm) deposit most of their energy. We report here first observations of thermospheric response to an X8.2 class flare on Mars measured by Imaging Ultraviolet Spectrograph on board the Mars Atmosphere Volatile EvolutioN spacecraft. We found that thermospheric temperatures increased by ~70 K at the time of the flare, although IUVS observations took place roughly 1 hr after the flare peak. The thermospheric temperatures retrieved by IUVS show that the flare‐induced heating was limited to the low and middle latitudes only. This is the first reported observation of latitudinal extent of atmospheric heating caused by a solar X‐class flare on Mars. Martian thermospheric temperature increases by ∼70 K in response to an X‐class solar flare and returns to its normal value in the next orbit (after  4.5 hr)Dayglow emissions show significant enhancement below and above the airglow peak due to increased flux of soft X‐ray and extreme ultraviolet photonsThermospheric heating due to the flare was limited to low and middle latitudes

We report the detection of bright aurora spanning Mars' nightside during the space weather event occurring in September 2017. The phenomenon was similar to diffuse aurora detected previously at Mars, but 25 times brighter and detectable over the entire visible nightside. The observations were made with the Imaging UltraViolet Spectrograph, a remote sensing instrument on the Mars Atmosphere and Volatile EvolutioN spacecraft orbiting Mars. Images show that the emission was brightest around the limb of the planet, with a fairly uniform faint glow against the disk itself. Spectra identified four molecular emissions associated with aurora, and limb scans show the emission originated from an altitude of ~60 km in the atmosphere. Both are consistent with very high energy particle precipitation. The auroral brightening peaked around 13 September, when the flux of solar energetic electrons and protons both peaked. During the declining phase of the event, faint but statistically significant auroral emissions briefly appeared against the disk of the planet in the form of narrow wisps and small patches. These features are approximately aligned with predicted open field lines in the region of strong crustal magnetic fields in Mars' southern hemisphere. A solar storm caused energetic particles from the Sun to strike Mars atmosphere and cause aurora. Unlike Earth, where aurora are limited to polar regions at the edges of our magnetic field, Mars aurora engulfed the entire planet. This is due to Mars' lack of a strong, global magnetic field. The solar storm caused aurora 25 times brighter than any previously observed. Mars Atmosphere and Volatile EvolutioN's Imaging UltraViolet Spectrograph obtained the first images of aurora on Mars. Mars does have weak magnetic fields locked into its wrist in some places. Imaging UltraViolet Spectrograph also obtained the first images of patchy aurora in those regions. The MAVEN spacecraft has obtained the first images of aurora on MarsMars aurora can be global in nature, due to its lack of a global magnetic fieldThe global aurora was triggered by a space weather event observed by many instruments and spacecraft

We report observations of Martian mesospheric ice clouds and thermospheric scale heights by the Imaging Ultraviolet Spectrograph on NASA's Mars Atmosphere and Volatile Evolution mission. The clouds are observed between 6 A.M. and 8 A.M. local time using mid‐UV limb observations between 60 and 80 km tangent altitude where ice particles that scatter sunlight can appear as detached layers near the equator. The equatorial longitudinal distribution shows populations of clouds near −110°E and −10°E as well as a population near 90°E, which does not have a clear precedent. The cloud populations indicate a wave 3 pattern near 70 km, which is confirmed by independent mesospheric temperature observations. Scale heights 100 km above the clouds derived from concurrent Imaging Ultraviolet Spectrograph (IUVS) observations also reveal a wave 3 longitudinal structure, suggesting that the temperature oscillations enabling the formation of mesospheric clouds couple to the upper atmosphere. The manuscript describes the observation of Martian mesospheric clouds between 60 and 80 km altitude by the Imaging Ultraviolet Spectrograph (IUVS) on NASA's MAVEN spacecraft. The cloud observations are uniquely obtained at early morning local times, which complement previous observations obtained primarily later in the diurnal cycle. Differences in the geographic distribution of the clouds from IUVS observations indicate that the local time is crucial for the interpretation of mesospheric cloud formation. We also report concurrent observations of upper atmospheric scale heights near 170 km altitude, which are diagnostic of temperature. These observations suggest that the dynamics enabling the formation of mesospheric clouds propagate all the way to the upper atmosphere. Martian mesospheric clouds are observed by solar scattering of midultraviolet sunlight from a fully illuminated atmosphereThe early morning mesospheric cloud observations are complementary to previous observations, which are primarily made in the afternoonThe data suggest that the geographic distribution of clouds is controlled by tides that propagate all the way to the upper atmosphere

We report results from a study of nitric oxide nightglow over the northern hemisphere of Mars during winter, the southern hemisphere during fall equinox, and equatorial latitudes during summer in the northern hemisphere based on observations of the δand γbands between 190 and 270 nm by the Imaging UltraViolet Spectrograph (IUVS) on the Mars Atmosphere and Volatile EvolutioN mission (MAVEN) spacecraft. The emission reveals recombination of N and O atoms dissociated on the dayside of Mars and transported to the nightside. We characterize the brightness (from 0.2 to 30 kR) and altitude (from 40 to 115 km) of the NO nightglow layer, as well as its topside scale height (mean of 11 km). We show the possible impact of atmospheric waves forcing longitudinal variability, associated with an increased brightness by a factor of 3 in the 140–200° longitude region in the northern hemisphere winter and in the −102° to −48° longitude region at summer. Such impact to the NO nightglow at Mars was not seen before. Quantitative comparison with calculations of the LMD‐MGCM (Laboratoire de Météorologie Dynamique‐Mars Global Climate Model) suggests that the model globally reproduces the trends of the NO nightglow emission and its seasonal variation and also indicates large discrepancies (up to a factor 50 fainter in the model) in northern winter at low to middle latitudes. This suggests that the predicted transport is too efficient toward the night winter pole in the thermosphere by ∼20° latitude north. We study nitric oxide nightglow at equinox, summer, and winter and compare to the LMD‐MGCM predictionsThis study reveals the seasonal control on the emission, as well as unexpected longitudinal variations caused by waves/tidesWe suggest future work on NO nightglow using GCMs and IUVS disk images and tangent limb data

Costimulation blockade (CoB) via belatacept is a lower‐morbidity alternative to calcineurin inhibitor (CNI)‐based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept and increased adhesion molecule expression. One such molecule is leukocyte function antigen (LFA)‐1. LFA‐1 exists in two forms: a commonly expressed, low‐affinity form and a transient, high‐affinity form, expressed only during activation. We have shown that antibodies reactive with LFA‐1 regardless of its configuration are effective in eliminating memory T cells but at the cost of impaired protective immunity. Here we test two novel agents, leukotoxin A and AL‐579, each of which targets the high‐affinity form of LFA‐1, to determine whether this more precise targeting prevents belatacept‐resistant rejection. Despite evidence of ex vivoand in vivoligand‐specific activity, neither agent when combined with belatacept proved superior to belatacept monotherapy. Leukotoxin A approached a ceiling of toxicity before efficacy, while AL‐579 failed to significantly alter the peripheral immune response. These data, and prior studies, suggest that LFA‐1 blockade may not be a suitable adjuvant agent for CoB‐resistant rejection. This study examines the use of belatacept with either depletion or inhibition of the high‐affinity form of LFA‐1 in a nonhuman primate model of kidney transplantation.

We present temperature maps derived from number density retrievals of carbon dioxide (CO2) for the upper mesosphere and lower thermosphere of Mars using limb observations from the Imaging Ultraviolet Spectrograph (IUVS) aboard NASA's Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft. We retrieve CO2densities using O(1S) metastable atoms that radiatively relax by emitting photons at 297.2 nm, producing a double‐peaked emission profile detectable by IUVS. Retrieved CO2densities are used to derive altitude profiles of temperature as a function of latitude, longitude, local time, season, dust activity, and solar activity. CO2density and temperature profiles retrieved using the O I 297.2 nm emission feature presented herein extend previous IUVS retrievals from 130–170 km down to 80 km. We validate retrieved CO2densities and derived temperatures using coincident measurements and corresponding data products produced by MAVEN IUVS, as available. Analysis of this comprehensive data set, which spans Mars years 32–36, shows (a) a consistently well‐defined mesopause at approximately 120 km, (b) warming at high pressures (typically below ∼100 km) for a variety of geophysical conditions, (c) asymmetry in temperatures at dawn and dusk with respect to latitude during different seasons (warmer temperatures at dawn during northern hemisphere autumn/winter and cooler temperatures at dusk during spring/summer), and (d) longitudinal waves with a dominant wave‐3 component in both the upper mesosphere and lower thermosphere, with lower (80–90 km) and upper (135–145 km) atmospheric waves about 65° out of phase. We show the first O I 297.2 nm emission‐derived temperature profiles extending from 80 to 150 km in the atmosphere of Mars obtained from observations by the Imaging Ultraviolet Spectrograph onboard NASA's Mars Atmosphere and Volatile EvolutioN spacecraft. This new analysis enables us to bridge the gap and improve our understanding of the coupling that occurs between the middle and upper atmospheres of Mars. Our analysis has revealed thermal variability in the Martian atmosphere with respect to latitude, longitude, local time, season, dust activity, and solar activity. As suggested by previous studies, waves generated in the lower atmosphere propagate to the upper atmosphere, coupling the atmospheric layers, and produce fluctuations in density (up to 40% locally) that can affect the background atmospheric temperature, which is a key parameter driving thermal escape of atomic hydrogen. The density and temperature data presented here provide an important but heretofore missing source of information that is needed to directly link weather and waves in the lower atmosphere to perturbations in composition and temperature in the upper atmosphere. Our analysis reveals a consistently well‐defined mesopause at approximately 120 kmWe observe an asymmetry in temperatures at dawn and dusk with respect to latitude during different seasonsLongitudinal waves with dominant wave‐3 component are characterized in both the upper mesosphere and lower thermosphere Our analysis reveals a consistently well‐defined mesopause at approximately 120 km We observe an asymmetry in temperatures at dawn and dusk with respect to latitude during different seasons Longitudinal waves with dominant wave‐3 component are characterized in both the upper mesosphere and lower thermosphere

Costimulation blockade with the fusion protein belatacept provides a desirable side effect profile and improvement in renal function compared with calcineurin inhibition in renal transplantation. This comes at the cost of increased rates of early acute rejection. Blockade of the integrin molecule leukocyte function‐associated antigen 1 (LFA‐1) has been shown to be an effective adjuvant to costimulation blockade in a rigorous nonhuman primate (NHP) model of islet transplantation; therefore, we sought to test this combination in an NHPrenal transplant model. Rhesus macaques received belatacept maintenance therapy with or without the addition of LFA‐1 blockade, which was achieved using a murine‐derived LFA‐1–specific antibody TS1/22. Additional experiments were performed using chimeric rhesus IgG1 (TS1/22R1) or IgG4 (TS1/22R4) variants, each engineered to limit antibody clearance. Despite evidence of proper binding to the target molecule and impaired cellular egress from the intravascular space indicative of a therapeutic effect similar to prior islet studies, LFA‐1 blockade failed to significantly prolong graft survival. Furthermore, evidence of impaired protective immunity against cytomegalovirus was observed. These data highlight the difficulties in translating treatment regimens between organ models and suggest that the primarily vascularized renal model is more robust with regard to belatacept‐resistant rejection than the islet model. In a nonhuman primate model of renal transplantation, the addition of short‐term LFA‐1 blockade to belatacept maintenance therapy fails to prolong graft survival beyond belatacept alone, contrary to previous results in other models, and impairs protective immunity, suggesting limited clinical applicability of this approach.

First direct observations of heating of the Mars neutral atmosphere by solar flares are presented in this study. Solar flares were detected using the Extreme Ultraviolet Monitor on board the Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft, and upper atmospheric temperature enhancements were determined by changes in the density scale height of Argon (Ar) made by the Neutral Gas and Ion Mass Spectrometer also on board MAVEN. We analyzed 14 M‐class or greater flares that occurred during the early part of the MAVEN mission in addition to a 30 day period of high flare activity during May 2015. We report that the Mars dayside upper atmosphere shows significant heating near the flare soft X‐ray peak; and it responds and recovers rapidly to heating from M‐class or larger flares. In addition, we present atmospheric density versus altitude profiles that were taken near the soft X‐ray peak of two flares. First observations of neutral heating at Mars due to solar flares are reportedThe upper atmosphere shows significant heating near the flare soft X‐ray peakThe Mars atmosphere responds and recovers rapidly to heating from M‐class flares

We report a comprehensive study of Mars dayglow observations focusing on upper atmospheric structure and seasonal variability. We analyzed 744 vertical brightness profiles comprised of ∼109,300 spectra obtained with the Imaging Ultraviolet Spectrograph (IUVS) aboard the Mars Atmosphere and Volatile EvolutioN (MAVEN) satellite. The dayglow emission spectra show features similar to previous UV measurements at Mars. We find a significant drop in thermospheric scale height and temperature between LS= 218° and LS= 337–352°, attributed primarily to the decrease in solar activity and increase in heliocentric distance. We report the detection of a second, low‐altitude peak in the emission profile of OI 297.2 nm, confirmation of the prediction that the absorption of solar Lyman alpha emission is an important energy source there. The CO2+UV doublet peak intensity is well correlated with simultaneous observations of solar 17–22 nm irradiance at Mars. Significant drop in thermospheric temperature between two Martian seasonsDetection of second layer of OI 297.2 nm emission below 100 kmStrong correlation between observed mid‐UV dayglow and simultaneously measured EUV flux at Mars

We identify molecular nitrogen (N2) emissions in the Martian upper atmosphere using the Imaging Ultraviolet Spectrograph (IUVS) on NASA's Mars Atmosphere and Volatile EvolutioN (MAVEN) mission. We report the first observations of the N2Lyman‐Birge‐Hopfield (LBH) bands at Mars and confirm the tentative identification of the N2Vegard‐Kaplan (VK) bands. We retrieve N2density profiles from the VK limb emissions and compare calculated limb radiances between 90 and 210 km against both observations and predictions from a Mars general circulation model (GCM). Contrary to earlier analyses using other satellite data, we find that N2abundances exceed GCM results by about a factor of 2 at 130 km but are in agreement at 150 km. The analysis and interpretation are enabled by a linear regression method used to extract components of UV spectra from IUVS limb observations. N2detected in the upper atmosphere of Mars by IUVS on MAVENTentative identification of N2Vegard‐Kaplan band emission confirmedN2Lyman‐Birge‐Hopfield bands identified on Mars for the first time

We present direct number density retrievals of carbon dioxide (CO2) and molecular nitrogen (N2) for the upper atmosphere of Mars using limb scan observations during October and November 2014 by the Imaging Ultraviolet Spectrograph on board NASA's Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft. We use retrieved CO2densities to derive temperature variability between 170 and 220 km. Analysis of the data shows (1) low‐mid latitude northern hemisphere CO2densities at 170 km vary by a factor of about 2.5, (2) on average, the N2/CO2increases from 0.042 ± 0.017 at 130 km to 0.12 ± 0.06 at 200 km, and (3) the mean upper atmospheric temperature is 324 ± 22 K for local times near 14:00. Retrieved CO2densities at 170 km vary by a factor of about 2.5On average, N2/CO2increases from 4% at 130 km to 12% at 200 kmMean Martian upper atmospheric temperature over the sampled time frame is 324 {±} 22 K

This study demonstrates that blockade of the ICOS–ICOS‐Ligand pathway, when used as monotherapy or paired with CD28‐B7 blockade, does not prolong renal allograft survival in a nonhuman primate kidney transplant model.

The authors provide an overview of the circumstances leading to loss of the critical T cell costimulatory molecule CD28, and they discuss the transplant‐relevant consequences of this sign of progressive T cell maturation.

The authors report on the use of an αvβ6 monoclonal antibody and its association with acute rejection when used in concert with calcineurin inhibitor–based immunosuppression in a nonhuman primate renal transplant model.

Belatacept is an inhibitor of CD28/B7 costimulation that is clinically indicated as a calcineurin inhibitor (CNI) alternative in combination with mycophenolate mofetil and steroids after renal transplantation. We sought to develop a clinically translatable, nonlymphocyte depleting, belatacept‐based regimen that could obviate the need for both CNIs and steroids. Thus, based on murine data showing synergy between costimulation blockade and mTOR inhibition, we studied rhesus monkeys undergoing MHC‐mismatched renal allotransplants treated with belatacept and the mTOR inhibitor, sirolimus. To extend prior work on costimulation blockade‐resistant rejection, some animals also received CD2 blockade with alefacept (LFA3‐Ig). Belatacept and sirolimus therapy successfully prevented rejection in all animals. Tolerance was not induced, as animals rejected after withdrawal of therapy. The regimen did not deplete T cells. Alefecept did not add a survival benefit to the optimized belatacept and sirolimus regimen, despite causing an intended depletion of memory T cells, and caused a marked reduction in regulatory T cells. Furthermore, alefacept‐treated animals had a significantly increased incidence of CMV reactivation, suggesting that this combination overly compromised protective immunity. These data support belatacept and sirolimus as a clinically translatable, nondepleting, CNI‐free, steroid‐sparing immunomodulatory regimen that promotes sustained rejection‐free allograft survival after renal transplantation.

Costimulation blockade (CoB), specifically CD28/B7 inhibition with belatacept, is an emerging clinical replacement for calcineurin inhibitor‐based immunosuppression in allotransplantation. However, there is accumulating evidence that belatacept incompletely controls alloreactive T cells that lose CD28 expression during terminal differentiation. We have recently shown that the CD2‐specific fusion protein alefacept controls costimulation blockade‐resistant allograft rejection in nonhuman primates. Here, we have investigated the relationship between human alloreactive T cells, costimulation blockade sensitivity and CD2 expression to determine whether these findings warrant potential clinical translation. Using polychromatic flow cytometry, we found that CD8+effector memory T cells are distinctly high CD2 and low CD28 expressors. Alloresponsive CD8+CD2hiCD28−T cells contained the highest proportion of cells with polyfunctional cytokine (IFNγ, TNF and IL‐2) and cytotoxic effector molecule (CD107a and granzyme B) expression capability. Treatment with belatacept in vitroincompletely attenuated allospecific proliferation, but alefacept inhibited belatacept‐resistant proliferation. These results suggest that highly alloreactive effector T cells exert their late stage functions without reliance on ongoing CD28/B7 costimulation. Their high CD2 expression increases their susceptibility to alefacept. These studies combined with in vivononhuman primate data provide a rationale for translation of an immunosuppression regimen pairing alefacept and belatacept to human renal transplantation.

Using the miniature swine large animal model we have attempted to determine the relationship between tolerance and the presence of donor cells in the bone marrow, thymus and lineages of peripheral blood in a series of hematopoietic cell transplant recipients receiving delayed donor allografts without immunosuppression. Twenty-two animals receiving hematopoietic cell transplantation and a delayed organ allograft were analyzed. Assays for presence of donor CFUs in bone marrow (by PCR), thymic chimerism (by FACS and PCRSouthern Blot), peripheral blood chimerism (by FACS), and in vitroresponsiveness to donor MHC were performed. Presence of donor BM CFUs, thymic chimerism and multilineage peripheral blood chimerism at the time of organ transplantation all correlated precisely with subsequent allograft tolerance (p < 0.001, p < 0.001, p < 0.005 respectively). These parameters were therefore accurate predictors (Positive Predictive Value (PPV) 100 in all) of tolerance. In vitroassays of responsiveness were also highly associated (p < 0.002, p < 0.002 respectively), but were not as accurate predictors of subsequent organ tolerance (CML PPV 80). Engraftment, as indicated by the presence of donor derived CFU in the bone marrow, detectable thymic chimerism and multilineage peripheral blood chimerism are reliable predictors of subsequent donor allograft acceptance in hematopoietic cell transplant recipients.

Sansalvamide A, a cyclic depsipeptide isolated from a marine fungus of the genus Fusarium, is composed of four hydrophobic amino acids (Phe, two Leu, Val) and one hydroxy acid ((S)-2-hydroxy-4-methylpentanoic acid; O-Leu) with five stereogenic centers all having S-stereochemistry. We have recently synthesized the corresponding cyclic peptide (Gu, W.; Liu, S.; Silverman, R. B. Organic Lett. 2002, 4, 4171−4174) and found that it too has antitumor activity. N-Methylation can enhance potency and selectivity for peptides. Consequently, here we synthesize 12 different N-methylated sansalvamide A peptide analogues and show that for several different tumor cell lines three of these analogues are more potent than the natural product; in pancreatic cells, sansalvamide A shows little activity, but the N-methylsansalvamide peptides are potent cytotoxic agents.

A detailed study has been conducted of the sorption of ethylene and 1-hexene in linear low density polyethylene (LLDPE) under typical gas phase LLDPE reactor conditions. The recently proposed osmotic ensemble hyperparallel tempering method is used to simulate ethylene and 1-hexene gas sorption in the polymer samples. Simulations are used to parametrize the PC−SAFT equation of state for calculation of gas sorption in amorphous polyethylene. A model for crystallite induced elastic constraints is adopted to modify the equation of state for description of gas sorption in polyethylene below melting point conditions. Single-component ethylene and 1-hexene gas sorption as well as ethylene/1-hexene gas co-sorption are studied in this work. It is observed that simulations provide an effective method to parametrize the PC−SAFT equation of state. In addition, since simulations and PC−SAFT assume a hypothetically amorphous polymer, a quantitative description of elastic effects for gas sorption in semicrystalline polyethylene emerges from our approach. The results are verified by comparison to the experimental results of Novak et al. [Novak et al. Manuscript in preparation, 2004].

We have studied the luminescence and spectroscopic properties of erythrosin B-doped sol-gel silica in aqueous solutions. Stern-Volmer plot was obtained for the phosphorescence intensity as a function of the dissolved oxygen content. Leaching of the dye molecules from the sol-gel matrix was examined by absorption spectroscopy. That acid-catalysed sol-gel materials leach slowly and based-catalysed sol-gel materials leach rapidly was revealed. Absorption data of the sol-gel materials indicated the existence of two leaching rate constants. Finally we demonstrated that the sol-gel oxygen sensor had a response time faster than 30 ms.

This paper identifies and ranks food items by estimating their contribution to the dietary exposure of the US population and 19 subpopulation groups. Contributions to dietary exposures to arsenic, cadmium, chromium, lead, nickel, benzene, chlorpyrifos, and diazinon are estimated using either the Dietary Exposure Potential Model (DEPM) approach, the National Human Exposure Assessment Survey Arizona (NHEXAS-AZ) approach or the combination of the two. The DEPM is a computer model that uses several national databases of food consumption and residue concentrations for estimating dietary. The DEPM approach ranks the contribution of food items to the total dietary exposure using two methods, the direct method that ranks contributions by population exposure magnitude and the weighted method that ranks by subpopulation exposure magnitude. The DEPM approach identifies highly exposed subpopulations and a relatively small number of food items contributing the most to dietary exposure. The NHEXAS-AZ approach uses the NHEXAS-AZ database containing food consumption data for each subject and chemical residues of a composite of food items consumed by each subject in 1 day during the sampling week. These data are then modeled to obtain estimates of dietary exposure to chemical residues. The third approach uses the NHEXAS-AZ consumption data with residue values from the national residue database. This approach also estimates percent contributions to exposure of each ranked food item for the Arizona population. Dietary exposures estimated using the three approaches are compared. The DEPM results indicate groups with highest dietary exposures include Nonnursing Infants, Children 1–6, Hispanic, Non-Hispanic White, Western, Northeast and Poverty 0–130%. The use of the Combined National Residue Database (CNRD) identifies 43 food items as primary contributors to total dietary exposure; they contribute a minimum of 68% of the total dietary exposure to each of the eight chemical residues. The percent contribution of ranked food items estimated using the NHEXAS samples is smaller than those obtained from the western US population via the DEPM. This indicates differences in consumption characteristics of the two groups with respect to the ranked food items. Six of 15 food items consumed by the NHEXAS-AZ subjects per day are ranked food items contributing between 56% and 70% of the estimated NHEXAS-AZ dietary exposure to each of the eight chemical residues. The difference between total dietary exposure estimates from the DEPM and NHEXAS-AZ approaches varies by chemical residue and is attributable to differences in sampling and analytical methods, and geographic areas represented by the data. Most metal exposures estimated using the NHEXAS consumption data with the CNRD have lower values than those estimated via the other approaches, possibly because the NHEXAS-AZ residue values are higher than the CNRD values. In addition, exposure estimates are seemingly affected by the difference in demographic characteristics and factors that affect types and amounts of food consumed. Efficient control strategies for reducing dietary exposure to chemical residues may be designed by focusing on the relatively small number of food items having similar ingredients that contribute substantively to the total ingestion exposure.Journal of Exposure Analysis and Environmental Epidemiology (2002) 12, 233–243 doi:10.1038/sj.jea.7500230

Abstract. The main arterial supply of the dorso-lumbar spinal cord is usually derived from a single anterior radiculo-medullary artery called the artery of Adamkiewicz and referred to as having a middle or low location. In some cases, the artery origin is higher, and a vessel which arises in the lower part of the region supplements the supply of the anterior spinal artery. In the literature, those arteries have been described as arising from L3 upwards, and have never been previously described angiographically, to our knowledge, below this level, although Suh and Alexander and Gililan have mentioned this eventuality. Of the 4,000 spinal cord angiographies performed in our institution, we report three cases in which the fourth lumbar artery flows into the anterior spinal artery of the conus medullaris. This anatomical variant may explain the sometimes devastating post-operative neurological complications from a spinal cord infarction on surgery of the lumbar spine or the abdominal aorta below L3.

Thermal treatment in air has a marked influence on the adsorption of oxygen and the photocatalytic activities of TiO2 (P25) for the oxidation of acetone in air. The photoactivity of TiO2 increases with the increase of thermal treatment temperature until 400 °C, above which more rutile is formed. On the basis of the photocatalytic performance of TiO2 thermally treated in a vacuum and the results of polycrystalline X-ray diffraction analysis, BET surface area, adsorption oxygen measurements and ESR spectra, the increase in photoactivity can be attributed to a catalyst surface with more adsorbed oxygen. This would generate more superoxide anion radicals under UV irradiation, resulting in a better separation of photoexcited electrons and holes.

The transcriptional coactivator p300 is essential for normal embryonic development and cellular differentiation. We have been studying the role of p300 in the transcription of a variety of genes, and we became interested in the role of this coactivator in the transcription of genes important in breast epithelial cell biology. From MCF-10A cells (spontaneously immortalized, nontransformed human breast epithelial cells), we developed cell lines that stably overexpress p300. These p300-overexpressing cells displayed reduced adhesion to culture dishes and were found to secrete an extracellular matrix deficient in laminin-5. Laminin-5 is the major extracellular matrix component produced by breast epithelium. Immunofluorescence studies, as well as experiments using normal matrix, confirmed that the decreased adhesion of p300-overexpressing cells is due to laminin-5-deficient extracellular matrix and not due to loss of laminin-5 receptors. Northern blots revealed markedly decreased levels of expression of two of the genes (designated LAMA3 and LAMC2) encoding the alpha3 and gamma2 chains of the laminin-5 heterotrimer in the cells that overexpress p300, whereas LAMB3 mRNA, encoding the third or beta3 chain of laminin-5, was not markedly reduced. Transient transfection experiments with a vector containing a murine LAMA3 promoter demonstrate that overexpressing p300 down-regulates the LAMA3 promoter. In summary, overexpression of p300 leads to down-regulation of laminin-5 production in breast epithelial cells, resulting in decreased adhesion.

Members of the NF-kappaB/RelB family of transcription factors play important roles in the regulation of inflammatory and immune responses. RelB, a member of this family, has been characterized as a transcription activator and is involved in the constitutive NF-kappaB activity in lymphoid tissues. However, in a previous study we observed an overexpression of chemokines in RelB-deficient fibroblasts. Here we show that RelB is an important transcription suppressor in fibroblasts which limits the expression of proinflammatory mediators and may exert its function by modulating the stability of IkappaBalpha protein. Fibroblasts from relb(-/-) mice overexpress interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in response to lipopolysaccharide (LPS) stimulation. These cells have an augmented and prolonged LPS-inducible IKK activity and an accelerated degradation which results in a diminished level of IkappaBalpha protein, despite an upregulated IkappaBalpha mRNA expression. Consequently, NF-kappaB activity was augmented and postinduction repression of NF-kappaB activity was impaired in these cells. The increased kappaB-binding activity and cytokine overexpression was suppressed by introducing RelB cDNA or a dominant negative IkappaBalpha into relb(-/-) fibroblasts. Our findings suggest a novel transcription suppression function of RelB in fibroblasts.

The establishment of CD4⁺ T cell tolerance requires that self-reactive thymocytes are negatively selected during thymic development. A threshold of antigen concentration appears to exist for both MHC class I- and class II-mediated negative selection, below which clonal deletion of a self-reactive transgenic TCR does not occur. Similarly, both the specificity and thymic concentration of MHC molecules affect the efficiency with which autoreactive thymocytes are deleted. However, this threshold for MHC class II concentration has not been well established. Here, we show that this threshold must be extraordinarily low. We have used the human lysozyme promoter to re-express an A_β^b cDNA on macrophages and other phagocytic myelomonocytic cells of class II-deficient A_β^b -/- mice. Surface expression of I-A^b could be detected on mature peritoneal macrophages and, minimally, on thymic dendritic cells; however, this level of expression was not sufficient for antigen-specific T cell activation. Nevertheless, when backcrossed onto an autoreactive K14 background, this minimal level of class II was sufficient to induce negative selection of a polyclonal self-reactive population. We conclude that provision of extremely low levels of class II to thymic dendritic cells confers on them the ability to mediate clonal deletion of autoreactive T cells.

Sn substitution for Ti in rutile TiO2has been found to increase the photoactivity of the rutile by up to 15 times for the oxidation of acetone. The activity increases with increasing Sn in Ti1−xSnxO2solid solution, and it peaks at a tin content of 0.075. Contrary to expectations, ζ potential measurements show that the poor photocatalytic activity of pure rutile is not due to the lack of hydroxyl groups on its surface. Photoexcited transient decay data relate the poor activity to the fast electron–hole recombination in rutile TiO2, and the addition of Sn to the rutile TiO2lattice can effectively slow down the recombination rate. Diffuse reflectance UV–vis spectra of the solid solutions reveal a blue shift, indicating an increase in the bandgap of the semiconductor. Based on these experimental results, we believe that the origin of the high photoactivity of Ti1−xSnxO2is the increase in its oxidation–reduction potential resulting from elevation of the solid solution's bandgap.

The establishment of CD4(+) T cell tolerance requires that self-reactive thymocytes are negatively selected during thymic development. A threshold of antigen concentration appears to exist for both MHC class I- and class II-mediated negative selection, below which clonal deletion of a self-reactive transgenic TCR does not occur. Similarly, both the specificity and thymic concentration of MHC molecules affect the efficiency with which autoreactive thymocytes are deleted. However, this threshold for MHC class II concentration has not been well established. Here, we show that this threshold must be extraordinarily low. We have used the human lysozyme promoter to re-express an A(beta)(b) cDNA on macrophages and other phagocytic myelomonocytic cells of class II-deficient A(beta)(b) -/- mice. Surface expression of I-A(b) could be detected on mature peritoneal macrophages and, minimally, on thymic dendritic cells; however, this level of expression was not sufficient for antigen-specific T cell activation. Nevertheless, when backcrossed onto an autoreactive K14 background, this minimal level of class II was sufficient to induce negative selection of a polyclonal self-reactive population. We conclude that provision of extremely low levels of class II to thymic dendritic cells confers on them the ability to mediate clonal deletion of autoreactive T cells.

As part of our fusion-product diagnostic development program, we have begun a series of experiments with 14 MeV neutrons generated in a Cockcroft-Walton accelerator. Two different detectors have been used to measure the neutron yield: a silicon SBD and a Cu foil. The energy of the emitted neutrons has been determined by using two spectrometers: the SBD and a3He proportional counter. The reaction rate is monitored, with about ±5% accuracy, by detecting the a particles from D + T ?n +a. The neutron yields obtained from the Si detector and the Cu activation had associated uncertainties of about ±15% and agreed well with the predicted values from a measurements.

Sample fabrication technique and characteristics of salicylideneaniline photochromic material and its applications as a temporary data storage medium in real-time holographic interferometry and high speed data recording are presented.

Host survival of herpes simplex virus type 1 (HSV-1) infection depends on the establishment of latent infections in both peripheral and central nervous systems. Strains of HSV-1 that are successful in escaping the immune response produce a lethal infection. We now report a possible mechanism of immune response evasion used by HSV-1. After intraocular inoculation of mice, HSV-1 strain F established a latent infection in the brain, whereas strain KOS did not. The immune response to HSV-1 infection (strains KOS and F) in the brain was characterized by induction of major histocompatibility complex class II expression and recruitment of CD4+ and CD8+ cells to highly restricted sites of intracerebral viral infection. Major histocompatibility complex class II antigen expression was primarily intracellular in strain KOS infection centers and at the cell surface in strain F infection centers. We propose that major histocompatibility complex class II-restricted viral-antigen presentation to T cells is interrupted during strain KOS infections, thereby allowing KOS infection to evade T-cell-mediated events that would normally protect the host from a lethal infection. Immunocompromised mice (athymic or irradiate mice) could not survive strain F infections; however, latent F infections were established in irradiated mice reconstituted with naive lymph node and spleen cells. These data suggest that class II-restricted presentation of viral antigens is required for the control of HSV-1 infections in the nervous system.

A Radiation Belt Monitor (RBM) sensitive to protons and electrons with energy ?0.5 MeV1 has been designed for the High Energy Transient Experiment (HETE) satellite in order to: first, control the on-off configuration of the experiments (i.e. those susceptible to proton damage); and second, to indicate the presence of proton and/or electron events that could masquerade as legitimate high energy photon events. One of the two RBM channels has an enhanced sensitivity to electrons. Each channel of the RBM, based on a PIN silicon diode, requires a typical power of 6 milliwatts. Tests have been performed with protons with energies from ~0.1 to 2.5 MeV (generated by a Cockcroft-Walton linear accelerator via the d(d,p)t reaction), and with electrons with energies up to 1 MeV (from a 1.0 µCi207Bi source).

A computational finite element model is developed herein for the purpose of predicting the evolution of delaminations in a laminated continuous fiber polymer matrix composite subjected to monotonically increasing loading. Because the temperature of interest is near the glass transition temperature of the matrix, the lamina are modelled as orthotropic linear viscoelastic materials. Crack growth is accommodated in the prediction via the incorporation of a cohesive zone model. Although the resulting algorithm is nonlinear and computationally intensive, it is demonstrated herein to be tenable for predicting delamination evolution. To illustrate this point, results are obtained for a quasi-isotropic [00,450,90°, -45°12laminate subjected to in-plane loading, as well as a crossply [9006/003], laminate subjected to out-of-plane loading. While results obtained herein are encouraging, they also indicate that further research is warranted to study potential anomalies.

Experimental results on striation instability in a self-sustained discharge-pumped XeCl laser are presented. The presence of HCl proves to be critical to the evolution of this particular mode of instability. The role of halogen donors in discharge instabilities of RGH lasers is discussed. That mixtures containing HCl will be susceptible to striation instability and those with F2 or NF3 will not is concluded.

Information was sought on the features of epithelial cells in the murine thymic medulla. The expression of major histocompatibility complex (MHC) molecules on medullary epithelium was defined by light microscopy with the aid of bone marrow chimeras and MHC-transgenic mice. A proportion of medullary epithelial cells was found to show conspicuously high expression of conventional MHC (H-2) class I (K, D, L) and class II (I-A, I-E) molecules. These cells express a high density of the Y-Ae epitope, a complex of an E alpha peptide and I-Ab molecules found on typical bone marrow-derived cells. MHC+ medullary epithelial cells show limited expression of I-O molecules, a class of atypical nonpolymorphic MHC-encoded class II molecules present on B cells. Other medullary epithelial cells express a high density of I-O molecules but show little or no expression of typical MHC class I or II molecules. MHC and I-O expression thus appear to subdivide medullary epithelial cells into two phenotypically distinct subsets. This applies in adults. In the embryonic thymus most medullary epithelial cells express both types of molecules.

T cell tolerance induction was examined in long-term H-2-heterozygous parent----F1 chimeras prepared with supralethal irradiation (1,300 rad). Although these chimeras appeared to be devoid of host-type APC, the donor T cells developing in the chimeras showed marked tolerance to host-type H-2 determinants. Tolerance to the host appeared to be virtually complete in four assay systems: (a) primary mixed lymphocyte reactions (MLR) of purified lymph node (LN) CD8+ cells (+/- IL-2); (b) primary MLR of CD4+ (CD8-) thymocytes; (c) skin graft rejection; and (d) induction of lethal graft-vs.-host disease by CD4+ cells. Similar tolerance was observed in chimeras given double irradiation. The only assay in which the chimera T cells failed to show near-total tolerance to the host was the primary MLR of post-thymic CD4+ cells. In this assay, LN CD4+ cells regularly gave a significant antihost MLR. The magnitude of this response was two- to fourfold less than the response of normal parental strain CD4+ cells and, in I-E(-)----I-E+ chimeras, was paralleled by approximately 70% deletion of V beta 11+ cells. Since marked tolerance was evident at the level of mature thymocytes, tolerance induction in the chimeras presumably occurred in the thymus itself. The failure to detect host APC in the thymus implies that tolerance reflected contact with thymic epithelial cells (and/or other non-BM-derived cells in the thymus). To account for the residual host reactivity of LN CD4+ cells and the incomplete deletion of V beta 11+ cells, it is suggested that T cell contact with thymic epithelial cells induced clonal deletion of most of the host-reactive T cells but spared a proportion of these cells (possibly low affinity cells). Since these latter cells appeared to be functionally inert in the thymus (in contrast to LN), we suggest that the thymic epithelial cells induced a temporary form of anergy in the remaining host-reactive thymocytes. This anergic state disappeared when the T cells left the thymus and reached LN.

There is a scarcity of descriptive data on the performance capacity of elite badminton players, whose fitness requirements are quite specific. The purpose of this paper is to investigate the physiological response of elite badminton players in a sport-specific fitness test. Twelve Hong Kong national badminton team players performed a field test on a badminton court. Six light bulbs were connected to a programming device causing individual bulbs to light up in a given sequence. The players were instructed to react to the flashes by running towards them, and striking shuttles mounted in the vicinity of the bulbs. Exercise intensity was controlled by altering the interval between successive lightings. A low correlation (r = 0.65) was found between the results of the field test and the rank-order list of subjects, based on an objective on-field physiological assessment and subjective ranking. This may be explained by the requirements of other factors besides physical fitness which contribute to success in elite level badminton competition. These factors may include, for example, technical skill, mental power, and aesthetic judgements on the court. Maximum mean (s.d.) heart rate data (187(8) beats.min-1) and blood lactate values (10.4(2.9) mmol.l-1) in this study showed that players were under maximal load during the field test. From the testing data, it seems reasonable to speculate that the intensity of level 3 (20 light pulses.min-1; 3.0 s.pulse-1) and level 4 (22 light pulses.min-1; 2.7 s.pulse-1) simulates the requirement of actual games energy expenditure of the Hong Kong badminton players exercising at close to their anaerobic threshold. The results also show that an estimate of fitness can be derived from measurements involving exercise closely resembling that which is specific for the sports activity in question. Improved training advice and guidance may result from such studies.

A theoretical model that accounts for fundamental plasma processes leading to the formation and decay of XeCs+ ionic excimers in high-pressure electron-beam-excited Ar/Xe/Cs mixtures was developed. Numerical calculations based on the model were performed. For atmospheric gas mixtures, the model predicts an intrinsic efficiency (energy stored in upper state/energy deposited) of 18%. Model calculations also indicate that while XeCs+ was predominantly formed via the rare-gas ion (Xe+) channel over the entire e-beam duration, the rare-gas metastable (Xe*) channel assumes dominance in the afterglow period.

Retinoic acid (RA) induces secretory differentiation in the wound epidermis of a regenerating amphibian limb. We investigated the role of individual RA receptor (RAR) types in the newt wound epidermis by introducing chimaeric RA/thyroid hormone (T3) receptors (chi alpha 1 and chi delta 1) that can be activated by T3. A biolistic particle delivery system was employed to transfect cells in the wound epidermis of a regenerating limb and approximately 10% of the cells in targeted surface areas expressed marker genes. Both chi alpha 1 and chi delta 1 were comparable in their ability to stimulate transcription of a synthetic reporter construct through a RA response element after activation with T3 in situ. This activation was also comparable to that obtained by the endogenous complement of RARs in the RA-treated, transfected wound epidermis. The RA-inducible WE3 antigen, a marker for secretory differentiation, which distinguishes the wound epidermis from normal skin (Tassava, R. A., Johnson-Wint, B. and Gross, J. 1986, J. Exp. Zool. 239, 229-240), was used to assess the functional role of chi alpha 1 and chi delta 1. Chimaeric receptors were transfected with an alkaline phosphatase marker gene, activated with T3, and the expression of both the marker and WE3 was analyzed by double-label immunofluorescence. Newt limbs transfected with chi delta 1 showed many double-labelled cells dependent on the presence of T3, whereas contralateral limbs transfected with an alkaline phosphatase marker lacking chimaeric receptor sequences did not.(ABSTRACT TRUNCATED AT 250 WORDS)

The rearrangement of Ig genes is known to be regulated by the production of H and kappa L chains. To determine whether lambda L chains have a similar effect, transgenic mice were produced with a lambda 2 gene. It was necessary to include the H chain enhancer, since a lambda gene without the added enhancer did not result in transgene expression. The lambda 2 transgene with the H enhancer was expressed in lymphoid cells only. The majority of the B cells of newborn transgenic mice produced lambda, whereas kappa + cells were reduced. Concomitantly, serum levels of kappa and kappa mRNA were diminished. By 2 wk after birth the proportion of kappa-expressing cells was dramatically increased. Adults had reduced proportions of B cells that produced lambda only, but the levels of lambda were still higher than in normal littermates. Also, kappa + cells were still lower than in normal mice. Analysis of hybridomas revealed that reduction of kappa gene rearrangement was the basis for the decreased frequency of kappa + cells. Furthermore, many cells also contained an unrearranged H chain allele. It was concluded that feedback inhibition by the lambda 2 together with endogenous H protein may have inhibited recombinase activity in early pre-B cells, leading to inhibition of both H chain and kappa gene rearrangement. Thus, lambda 2 can replace kappa in a feedback complex. The levels of serum lambda 1 and, to a lesser degree, of spleen lambda 1 mRNA were reduced in the lambda 2 transgenic mice. However, the proportion of hybridomas with endogenous lambda gene rearrangement was at least as high as in normal mice. It was therefore concluded that the suppression of functional lambda 1 may be a consequence of decreased selection of endogenous lambda-producing cells because of the excess of transgenic lambda. The escape of kappa-producing cells from feedback inhibition may be the result of several mechanisms that operate to varying degrees, among them: (a) kappa rearrangement during a period in which the recombinase is still active after appearance of a lambda 2/mu stop signal; (b) a B cell lineage that is not feedback inhibited at the pre-B cell stage; (c) subthreshold levels of transgenic lambda 2 in some pre-B cells; and (d) loss of the lambda 2 transgenes in rare pre-B cells.