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Both predicting and controlling disruptions are critical and urgent issues for ITER as some disruptions with a short warning time may be unavoidable. For these cases, a rapid response disruption mitigation system (DMS) referred to as the electromagnetic particle injector (EPI) is being developed. The primary advantages of the EPI are its fast response time and high velocity, which have been demonstrated in offline experiments (Raman et al., 2021). The EPI is capable of accelerating a metallic sabot electromagnetically using a rail gun to the required velocities (>2 km/s) within 2 ms. Two high-field racetrack magnets able to generate fields over 2 T are positioned above and below the rails to permit high velocity at low rail currents, a requirement to minimize electrode erosion. At the end of the acceleration phase, a sabot capture mechanism retains the spent sabot inside the vacuum chamber that houses the EPI. At this point, it releases well-defined microspheres, or a shell pellet, of a radiative payload into the disrupting plasma. A remotely operated sabot loading system positioned behind the injector contains several pre-equipped sabots that can be loaded by an operator from the tokamak control room. The injector is interfaced to the tokamak through a guide tube attached to the front of the EPI vacuum chamber. The advantages of the EPI system over other DMSs under consideration are described in conjunction with the details of an EPI system designed for near-term test on an existing large tokamak.

The accumulation of cull potato piles is a concern because they take up space and harbor potato-associated pathogens. Black soldier fly, Hermetia illucens, larvae are an increasingly popular agent for converting organic wastes into ingredients for animal feeds. In this investigation, their ability to process cull potato waste was assessed. Potato tubers were suitable for larval development, but only following their disintegration through thermal or mechanical means. Optimal bioconversion was observed when potato substrate was provided at a rate of 1 g per larva. The presence of ground turkey meat and sawdust was generally beneficial to larval development and biomass accumulation. The presence of potato foliage in diet showed no negative effects on larval development and there was no glycoalkaloid bioaccumulation in larval tissues. Evidence from this investigation suggests that culled potato waste may be recycled using black soldier fly larvae.

Saline/sodic soils are often remediated by applying gypsum, improving drainage, and irrigating with high quality water. However, these management approaches may not be effective or feasible in dryland soils supersaturated with gypsum. A field study, conducted between 2017 and 2021, investigated the effect of phytoremediation on soil and plant health in a landscape containing productive, transition, and saline/sodic soils. Phytoremediation treatments–corn (Zea mays) and two perennial grass mixes (mix 1 slender wheatgrass [Elymus trachycaulus] and beardless wildrye [Leymus triticoides], and mix 2 slender wheatgrass, creeping meadow foxtail [Alopecurus arundinaceus], western wheatgrass [Agropyron smithii], and green wheatgrass [Elymus Hoffmannii])-were planted and compared with a no-plant control treatment across three soil zones. Perennial grasses were dormant seeded in the winter of 2017 and 2018, and corn was grown in 2018, 2019, and 2020. Soil samples (0 to 15 cm) were collected on July 24, 2018, July 23, 2019, July 24, 2020, and April 15, 2021. Across soil zones, corn production was 5,990 (grain + stover), 3,900 (stover only), and 6,150 (grain + stover) kg ha-1in 2018, 2019, and 2020, respectively, whereas perennial grass biomass yields averaged 1,220, 9,065, and 7,375 kg ha-1in 2018, 2019, and 2020, respectively. Due to high rainfall that occurred from the fall of 2018 through the summer of 2019, the depth to the water table decreased and the soil electrical conductivity (EC1:1) (-0.83 ± 0.149 dS m-1) and exchangeable sodium (Na+) (-656 ± 220) decreased in all treatments. In addition, from 2018 to 2019, the risk of soil dispersion (lower Na+/EC1:1ratio) was less in treatments with growing plants (p= 0.02) than plots without plants. With drier conditions from the fall of 2019 through the spring of 2021, the depth to groundwater increased, the EC1:1decreased in the transition soil but increased in the saline/sodic soil (p= 0.001), and the Na+/EC1:1ratio increased in the productive and transition soils and was static or decreased in the saline/sodic soil (p= 0.001). In conclusion, this and related work showed that phytoremediation when combined with high natural rainfall reduced soil EC1:1and the exchangeable Na+in all soils; however, these benefits may be short lived, and as the water tables dropped in 2020, EC1:1increased in the saline/sodic zones. Laboratory and linked research from the study site also showed that fertilizing saline sodic soils can result in very high nitrous oxide (N2O) emissions, and reseeding degraded soil to perennial plants provides soil cover that reduces the risk of erosion and provides habitat for wildlife.

Coordinated skills such as speech or dance involve sequences of actions that follow syntactic rules in which transitions between elements depend on the identities and order of past actions. Canary songs consist of repeated syllables called phrases, and the ordering of these phrases follows long-range rules1in which the choice of what to sing depends on the song structure many seconds prior. The neural substrates that support these long-range correlations are unknown. Here, using miniature head-mounted microscopes and cell-type-specific genetic tools, we observed neural activity in the premotor nucleus HVC2–4as canaries explored various phrase sequences in their repertoire. We identified neurons that encode past transitions, extending over four phrases and spanning up to four seconds and forty syllables. These neurons preferentially encode past actions rather than future actions, can reflect more than one song history, and are active mostly during the rare phrases that involve history-dependent transitions in song. These findings demonstrate that the dynamics of HVC include ‘hidden states’ that are not reflected in ongoing behaviour but rather carry information about prior actions. These states provide a possible substrate for the control of syntax transitions governed by long-range rules.

Black soldier fly larvae, Hermetia illucens(L.), are used to convert organic waste streams into insect-based animal feeds. We tested their ability to retain alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from feeding substrates, which has important implications for their use in aquaculture. When supplementing a chicken feed diet with increasing concentrations of salmon oil (0–42%) over an increasing number of days (0–8), the concentrations of the three omega-3 acids in larvae increased significantly. Larval survival and biomass accumulation were not affected. Supplementing a chicken feed diet with increasing concentrations (0–14%) of Tetraselmis chuiButcher (Chlorodendrales: Chlorodendraceae) microalgae paste also significantly increased ALA and EPA contents of the harvested larvae. However, microalgae also decreased survival, harvested biomass, and individual growth of larvae feeding on the diet with the highest supplement concentration (14%). DHA was not detected in any microalgae diet or subsequent larval tissue samples. All three omega-3 polyunsaturated fatty acids tested in this study were accumulated in dose-dependent manner, with quadratic, and occasionally linear, equations providing the best description of the observed relationships. There were significant negative correlations between several fatty acids, indicating that they may replace one another in living larvae. Our findings confirm that black soldier fly larvae can retain ingested fatty acids and change fatty acid profiles in their tissues accordingly. However, optimizing nutrient content of harvestable larvae is likely to be more complicated than simply enriching their diets with omega-3 fatty acids.

Motor skills can be maintained for decades, but the biological basis of this memory persistence remains largely unknown. The zebra finch, for example, sings a highly stereotyped song that is stable for years, but it is not known whether the precise neural patterns underlying song are stable or shift from day to day. Here we demonstrate that the population of projection neurons coding for song in the premotor nucleus, HVC, change from day to day. The most dramatic shifts occur over intervals of sleep. In contrast to the transient participation of excitatory neurons, ensemble measurements dominated by inhibition persist unchanged even after damage to downstream motor nerves. These observations offer a principle of motor stability: spatiotemporal patterns of inhibition can maintain a stable scaffold for motor dynamics while the population of principal neurons that directly drive behavior shift from one day to the next.

A high average power diode pumped solid state laser is used to pump large aperture Ti:sapphire enabling high average power chirped pulse amplification. After compression, over a petawatt of peak power will be used to generate fusion ions and neutrons for materials testing of first wall and final optics candidates.

AbstractCritical issues and ion beam requirements are explored for fast ignition using ion beams to provide fuel compression using indirect drive and to provide separate short-pulse ignition heating using direct drive. Several ion species with different hohlraum geometries are considered for both accelerator-produced and laser-produced ion ignition beams. Ion-driven fast ignition targets are projected to have modestly higher gains than with conventional heavy ion fusion and may offer some other advantages for target fabrication and for use of advanced fuels. However, much more analysis and additional experiments are needed before conclusions can be drawn regarding the feasibility for meeting the ion beam transverse and longitudinal emittances, focal spots, pulse lengths, and target standoff distances required for ion-driven fast ignition.

Background & Aims: Patients with cirrhosis have an increased risk for cholelithiasis but also have an increased risk for morbidity and mortality after cholecystectomy. Current preoperative assessment of surgical risk is imprecise. Our aims were to identify preoperative factors that would accurately predict the risk for cholecystectomy in patients with cirrhosis. Methods: Preoperative clinical or biochemical parameters were determined for 33 patients with cirrhosis and 31 age- and sex-matched patients without cirrhosis. The use of these parameters and of the Child-Pugh and model for end-stage liver disease (MELD) scores as preoperative predictors of outcome after surgery were assessed. Results: There were 2 deaths, both in cirrhotic patients. The overall risk for morbidity or mortality was increased in cirrhotic patients compared with controls. Postoperative morbidity was significantly associated with preoperative increases of international normalized ratio >1.2, bilirubin >1.0 mg/dL, creatinine >1.4 mg/dL, and a decreased platelet count <150 x 10^3/mL. The MELD and Child-Pugh scores accurately predicted postoperative morbidity, with an area under the curve of 0.938 and 0.839, respectively. A preoperative MELD score of >=8 had a sensitivity of 91% and a specificity of 77% for predicting postoperative morbidity. Persons with a MELD score of >=8 had increased 30- and 90-day global charges and increased blood product usage. Conclusions: Preoperative biochemical parameters, international normalized ratio, bilirubin, platelets, and creatinine can predict increased morbidity in cirrhotic patients. A MELD score of >=8 identifies a group at high risk for postoperative morbidity after cholecystectomy.

In contrast to the large mass, complexity and recirculating power of conventional drivers for inertial confinement fusion (ICF), antiproton annihilation offers a specific energy of 90 MJ µg⁻¹ and thus a unique form of energy packaging and delivery. In principle, antiproton drivers could provide a profound reduction in system mass for advanced space propulsion by ICF. We examine the physics underlying the use of antiprotons (

Excess sludge generated in industrial wastewater treatment was converted to soluble organic products and gases in a nitrolysis reaction. The conversion of industrial excess sludge reached 80% by mass (99% conversion after removal inerts from the calculation). The most instrumental operating parameters in increasing this conversion were reaction temperature and acid/sludge ratio in the reactor. The reduction in mass and volume of the excess sludge shows promise in reducing the liability and cost associated with disposal. The production of organic acids (e.g., acetic acid) was also demonstrated, leading to an even more promising treatment alternative for excess sludge. The operating parameters that affect the production of organic acids were also studied. The reaction rate of the process was compared to a previously developed model, showing good agreement. The stoichiometry of the process was investigated, showing more than 90 mg of acetic acid and more than 50 mg of formic acid produced per gram of industrial excess sludge reacted.

The public's misconception of what the singlepayer system is (and how it can help them) has made talk of a U.S. national health plan a challenging one. Here's how RNs can dispel myths with facts. [ABSTRACT FROM AUTHOR]

This research is focused on developing a process called nitrolysis for treatment of excess sludge from wastewater processing. In this process, the excess sludge is treated with nitric acid (up to 11 wt %) at an elevated temperature (>160 °C) and pressure (100 psig). The result of this treatment is a substantial conversion of the excess sludge to soluble organic. This conversion reduces the viscosity and solids content of the excess sludge stream, thus reducing the disposal costs. The products of the reaction include biodegradable organics that may be recycled to the wastewater treatment process. Other products include potentially recoverable organic acids such as acetic acid. These acids are produced at about 0.15 g/g of dry excess sludge that reacts. This study investigates the operating parameters that could improve the conversion of excess sludge to products and/or biodegradable soluble organics. The parameters used in this study included temperature, acid concentration, sludge concentration, and reaction time. An initial factorial study of these parameters indicated that the acid and sludge concentrations were the most influential in the conversion process. Increasing the acid concentration would convert more of the excess sludge to product. Although the initial study did not show a change in conversion above 160 °C, decreasing the temperature below 160 °C showed a significant decrease in the excess sludge conversion from 75% to 22%. The lower acid concentration also showed a significant drop in conversion, decreasing from >60% at 11.2 wt % acid to 10% at 0.4 wt % acid. Chemical oxygen demand and total organic carbon tests were used to verify the material balance around the reactor with better than 90% closure. These tests also demonstrated that the initial hydrolysis step in the biomass degradation is very rapid (&lt;5 min).

This investigation assessed the ability of the zoonotic A/chicken/Hong Kong/220/97 (chicken/Hong Kong) (H5N1) highly pathogenic avian influenza virus to infect and cause disease in zebra finches (Taeniopygia guttata), house finches (Carpodacus mexicanus), house sparrows (Passer domesticus), European starlings (Sternus vulgaris), and budgerigars (Melopsittacus undulatus) after intranasal administration. Zebra finches were the most severely affected of the five species, demonstrating anorexia, depression, and 100% mortality within 5 days of inoculation. Gross lesions in this species were absent or only mild. But histologic lesions and the corresponding viral antigen were observed in multiple organs, especially in the nasal cavity, brain, pancreas, spleen, adrenal glands, and ovary. Significant morbidity and mortality also were observed in both house finches and budgerigars. Affected birds of these two species demonstrated anorexia, depression, and neurologic signs and typically were moribund or dead within 2 days of the onset of clinical signs. Gross lesions were mild or absent in house finches and budgerigars. Histologically, the brain and pancreas were the most consistently and severely affected organs in house finches. The brain was the most affected organ in budgerigars. Unlike these three species, house sparrows suffered only mild transient depression, had no mortality, and lacked gross lesions. Viral antigen and microscopic lesions were observed only in the heart and testicle of a minority of birds of this species. Starlings demonstrated neither clinical disease nor mortality and lacked gross and histologic lesions. Viral antigen was not observed in any of the collected tissues from starlings. These results indicate that there is significant variation in the pathogenicity of the chicken/Hong Kong virus for different species of birds, including species within the same order. In addition, neurotropism is a recurrent feature among birds that eventually succumb to infection.

The Innovative Confinement Concepts Workshop, ICC2002, provided a forum for presentations and exchange of ideas on the science and status of innovative concepts in the U.S. Fusion Energy Program. The workshop, held at the University of Maryland on January 22–24, 2002, included oral presentations addressing the important science and status of the concepts, posters focussed on details of the work, a skunkworks for novel ideas, and breakout sessions preparing for the July 2002 fusion energy Snowmass meeting. This report summarizes the oral presentations. A web site (https://wormhole.ucllnl.org/ICC2002/) has been established with the abstracts and many of the presentations, both oral and poster, from the workshop.

The initiation of gene expression in response to Drosophila receptor tyrosine kinase signaling requires the nuclear import of the MAP kinase, D-ERK. However, the molecular details of D-ERK translocation are largely unknown. In this regard, we have identified D-Importin-7 (DIM-7), the Drosophila homolog of vertebrate importin 7, and its gene moleskin. DIM-7 exhibits a dynamic nuclear localization pattern that overlaps the spatial and temporal profile of nuclear, activated D-ERK. Co-immunoprecipitation experiments show that DIM-7 associates with phosphorylated D-ERK in Drosophila S2 cells. Furthermore, moleskin mutations enhance hypomorphic and suppress hypermorphic D-ERK mutant phenotypes. Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7. Mutations in the Drosophila Importin beta homolog Ketel, also reduce the nuclear localization of activated D-ERK. Together, these data indicate that DIM-7 and Ketel are components of the nuclear import machinery for activated D-ERK.

Direct bird-to-human transmission, with the production of severe respiratory disease and human mortality, is unique to the Hong Kong-origin H5N1 highly pathogenic avian influenza (HPAI) virus, which was originally isolated from a disease outbreak in chickens. The pathobiology of the A/chicken/Hong Kong/ 220/97 (H5N1) (HK/220) HPAI virus was investigated in chickens, turkeys, Japanese and Bobwhite quail, guinea fowl, pheasants, and partridges, where it produced 75-100% mortality within 10 days. Depression, mucoid diarrhea, and neurologic dysfunction were common clinical manifestations of disease. Grossly, the most severe and consistent lesions included splenomegaly, pulmonary edema and congestion, and hemorrhages in enteric lymphoid areas, on serosal surfaces, and in skeletal muscle. Histologic lesions were observed in multiple organs and were characterized by exudation, hemorrhage, necrosis, inflammation, or a combination of these features. The lung, heart, brain, spleen, and adrenal glands were the most consistently affected, and viral antigen was most often detected by immunohistochemistry in the parenchyma of these organs. The pathogenesis of infection with the HK/220 HPAI virus in these species was twofold. Early mortality occurring at 1-2 days postinoculation (DPI) corresponded to severe pulmonary edema and congestion and virus localization within the vascular endothelium. Mortality occurring after 2 DPI was related to systemic biochemical imbalance, multiorgan failure, or a combination of these factors. The pathobiologic features were analogous to those experimentally induced with other HPAI viruses in domestic poultry.

AbstractWith 180 MJ/μg, antiprotons offer the highest stored energy per unit mass of any known entity. The use of antiprotons to promote fast ignition in an inertial confinement fusion (ICF) capsule and produce high target gains with only modest compression of the main fuel is investigated. Unlike standard fast ignition where the ignition energy is supplied by an energetic, short pulse laser, the energy here is supplied through the ionization energy deposited when antiprotons annihilate at the center of a compressed fuel capsule. This can be considered in-situ fast ignition as it obviates the need for the external injection of the ignition energy. In the first of two candidate schemes, the antiproton package is delivered by a low-energy ion beam. In the second, autocatalytic scheme, the antiprotons are preemplaced at the center of the capsule prior to compression. In both schemes, we estimate that ~1012antiprotons are required to initiate fast ignition in a typical ICF capsule and show that incorporation of a thin, heavy metal shell is desirable to enhance energy deposition within the ignitor zone. In addition to eliminating the need for a second, energetic fast laser and vulnerable final optics, this scheme would achieve central ignition without reliance on laser channeling through halo plasma or Hohlraum debris. However, in addition to the practical difficulties of storage and manipulation of antiprotons at low energy, the other large uncertainty for the practicality of such a speculative scheme is the ultimate efficiency of antiproton production in an external, optimized facility. Estimates suggest that the electrical wall plug energy per pulse required for the separate production of the antiprotons is of the same order as that required for the conventional slow compression driver.

The homeotic gene, Ultrabithorax (Ubx) is involved in specifying the identities of several segments in the fly Drosophila melanogaster. The structures of over 60 independent Ubx cDNAs have been examined. There are two major species of transcripts, 3.2 and 4.3 kb in length, which are produced by alternate sites of polyadenylation. Differential splicing gives rise to at least five variant Ubx proteins. The variant forms share common 5′ and 3′ exons but differ in their small internal ‘micro’ exons. Additional variation is generated by two separate splice donor sites at the end of the common 5′ exon, situated 27 bp apart. Northern hybridization and S1 nuclease protection studies of RNA from various developmental stages and tissue types reveal that the alternate splicing and the choice of polyadenylation site are each differentially regulated in both a temporal and a tissue specific manner. Additional transcripts were found just downstream of the Ubx transcription unit, which may be products of the lethal left of bithorax gene (llb).

Release of the excitotoxic amino acids, glutamate and aspartate, from the ischemic rat cerebral cortex was compared in two models; the seven vessel occlusion model (7VO) of complete cerebral ischemia and the four vessel occlusion model (4VO) of incomplete cerebral ischemia. Amino acid efflux into cortical superfusates was measured using cortical cups placed on both hemispheres. Whereas a 20 min period of ischemia causes a pronounced release of glutamate and aspartate from the 4VO model, efflux was significantly reduced in the 7VO model. Release of the inhibitory transmitter GABA, was similar in the two models. This result suggests that excitotoxic amino acid efflux into the extracellular spaces of the cerebral cortex may be enhanced by the residual blood flow in an incomplete ischemia.

The Tokamak Physics Experiment is designed to develop the scientific basis for a compact and continuously operating tokamak fusion reactor. It is based on an emerging class of tokamak operating modes, characterized by beta limits well in excess of the Troyon limit, confinement scaling well in excess of H-mode, and bootstrap current fractions approaching unity. Such modes are attainable through the use of advanced, steady state plasma controls including strong shaping, current profile control, and active particle recycling control. Key design features of the TPX are superconducting toroidal and poloidal field coils; actively-cooled plasma-facing components; a flexible heating and current drive system; and a spacious divertor for flexibility. Substantial deuterium plasma operation is made possible with an in-vessel remote maintenance system, a lowactivation titanium vacuum vessel, and shielding of ex-vessel components. The facility will be constructed as a national project with substantial participation by U.S. industry. Operation will begin with first plasma in the year 2000.

A rapid modified high performance liquid chromatographic (HPLC) method was developed for the analysis of the benzimidazole fungicide thiabendazole (TBZ) in fresh produce. Changes were in the extraction technique and HPLC mobile phase. TBZ was extracted from the produce by either polytroning 10 g in 20 mL of methanol for 3 minutes or shaking, by hand, a 5 or 10 g sample in 20 mL of methanol for 10 minutes. A 50 μL aliquot was injected directly into an isocratic fluorescent HPLC system. Total analysis time ranged from 8 to 15 minutes per sample depending upon the extraction procedure employed. Percent recoveries averaged 90% with excellent reproducibility (%CVs from 0 to 18). For enzyme linked immunosorbent assay (ELISA) confirmation a 0.1 mL aliquot of the sample was removed and evaporated to dryness under air. The residue was dissolved in water before performing the ELISA.

Abstract: Because of the potential application to power production, it is important to investigate a wide range of possible means to achieve nuclear fusion, even those initially appearing infeasible. In antiproton-catalyzed fusion, the negative antiproton shields the repulsion between the positively charged nuclei of hydrogen isotopes, allowing a much higher level of penetration through the repulsive Coulomb barrier and greatly enhancing the fusion cross section. With their more compact wave function, the more massive antiprotons offer much more shielding than negative muons. If the antiproton could exist in the ground state with a nucleus for a sufficient time without annihilating, the fusion cross sections are so enhanced at low energies that at room temperature, values up to about 1000 barns (d + t) would be possible. Unfortunately, the cross section for antiproton annihilation with the incoming nucleus is even higher. A model giving an upper bound for the fusion to annihilation cross section ratio for all relevant energies indicates that each antiproton will catalyze no more than about one fusion. Since the energy to make one antiproton greatly exceeds the fusion energy released, this level of catalysis is far from adequate for power production.

The 1993 declassification of virtually all inertial confinement fusion (ICF) target information relevant to fusion energy development, and demonstrable successes in the physics and technology related to ICF, have laid the ground work for a development plan for an Inertial Fusion Energy (IFE) programme. The ICF programme, funded by the Defense Program in the USA, has clearly demonstrated there is sufficient confidence in ignition and gain to proceed with construction of the National Ignition Facility, which will test the detailed physics of targets suitable for IFE. In September 1998, the facility was about 40 complete and on schedule and within budget for completion in 2003. X–ray–drive ignition is planned for 2007, followed by direct–drive ignition experiments. The other major elements of an IFE development programme, namely, driver, target factory, and target chamber developments can be investigated separately in affordable programmes. Although much work remains, there are concepts for adequately high driver efficiency and target gain, target cost and target chamber survivability to make an exploratory programme in IFE attractive.

Formation of the tail region of the Drosophila larva requires the activities of the terminal class genes. Genetic and molecular analyses of these genes suggests that localized activation of the receptor tyrosine kinase torso at the posterior egg pole triggers a signal transduction pathway. This pathway, mediated through the serine/threonine protein kinase D-raf and the protein tyrosine phosphatase corkscrew, controls the domains of expression of the transcription factors tailless and huckebein. In this paper, we report the molecular and developmental characterization of mutations in the D-raf gene. We show that mutations that alter conserved residues known to be necessary for kinase activity are associated with a null phenotype, demonstrating that D-raf kinase activity is required for its role in torso signaling. Another mutation, D-rafPB26, which prematurely truncates the kinase domain shows a weaker maternal effect phenotype that is strikingly similar to the corkscrew maternal effect phenotype, suggesting that a lower amount of kinase activity decreases the terminal signaling pathway. Finally, molecular and developmental characterization of two mutations that affect the late D-raf zygotic function(s) implies a novel role for D-raf in cell fate establishment in the eye. One of these mutations, D-rafC110, is associated with a single amino acid change within the putative D-raf regulatory region, while the other, D-rafHM-7, most likely reduces the wild-type amount of D-raf protein.

The nucleotide exchange process is one of the key activation steps regulating the ras protein. This report describes the development of potent, non-nucleotide, small organic inhibitors of the ras nucleotide exchange process. These inhibitors bind to the ras protein in a previously unidentified binding pocket, without displacing bound nucleotide. This report also describes the development and use of mass spectrometry, NMR spectroscopy and molecular modeling techniques to elucidate the structure of a drug-protein complex, and aid in designing new ras inhibitor targets.

By means of low-stringency cross-species hybridization to Southern DNA blots, human c-jun sequences were used to identify a unique Drosophila melanogaster locus (Djun). The predicted DJun protein is highly homologous to members of the mammalian Jun family in both the DNA binding and leucine zipper regions. Djun was mapped by in situ hybridization to position 46E of the second chromosome. It encodes a 1.7-kilobase transcript constitutively expressed at all developmental stages. Functionally, Djun in cooperation with mouse c-fos can trans-activate activator protein 1 DNA binding site when introduced into mammalian cells. Taken together, these data suggest that Djun, much like its mammalian homolog, may activate transcription of genes involved in regulation of cell growth, differentiation, and development. Furthermore, the identification of Djun allows one to exploit the genetics of Drosophila to identify genes in signal transduction pathways involving Djun and thus c-jun.

Monte Carlo methods are employed to compute surface heat fluxes at the first walls of three representative tandem mirror reactors: TDF, TASKA-M, and MARS, resulting from charge-exchange (CX) of high power neutral beams with the fusion plasmas. The full three-dimensional nature of the anisotropic interaction processes of neutral beams with mirror-confined plasmas is retained in the calculations, and resulting CX heat fluxes are mapped both azimuthally and axially on the first wall surfaces. The angular distribution of heat fluxes at the first wall shows strong backward-peaking for TDF with maximum power densities of ~ 2.4 kW cm-2 occurring at 180° relative to the incident beam direction. By contrast, the angular distributions for TASKA-M and MARS exhibit strong forward-peaking, resulting in hot spots of 1140 and 700 W cm-2, respectively, at the first wall. Physical arguments are presented for the behavior of these CX heat flux distributions in terms of the plasma and beam parameters of each system. Particular emphasis is given to the engineering implications of the results and methods for ameliorating these high first wall heat fluxes are discussed.

The orang‐utan Pongo pygmaeusssp is an Asian great ape which is now only found on the islands of Borneo and Sumatra. In North America in 1982 a Species Survival Plan (SSP) programme was initiated which, over the next 100 years, aims to maintain c. 91% of the original genetic diversity of the captive populations of Bornean Pongo pygmaeus pygmaeusand c. 94% of Sumatran Pongo pygmaeus abeliiorang‐utans. There is some controversy over the genetic evidence of distinct subspeciation but in 1985 the SSP adopted a moratorium on the reproduction of subspecific hybrids. The SSP has encouraged various initiatives in North American zoos which house orang‐utans to provide direct support to in situfield conservation and research projects in Indonesia and Malaysia, including a fund‐raising programme at Zoo Atlanta and a Population and Habitat Viability Analysis (PHVA) in Sumatra.

Hostility has been associated with coronary heart disease mortality. To assess possible mechanisms linking hostility to coronary heart disease risk, the authors conducted analyses in a cross-sectional study from data collected in 1985 and 1986 on 5,115 young adults, aged 18-30 years, black and white, male and female, in four large urban areas of the United States. The results show that higher levels of hostility as determined by the Cook-Medley Hostility Scale were strongly associated with tobacco and marijuana smoking, increased alcohol consumption, and greater caloric intake in both blacks and whites and in both men and women. The increased caloric consumption was evident in the higher waist/hip ratios, particularly in men (p less than 0.05). The associations were particularly strong (p less than 0.001) for tobacco cigarette smoking and marijuana smoking, with roughly a 1.5 times higher prevalence in the top hostility quartile compared with the bottom quartile after adjusting for age and education. Hostility levels were not related to the percentage of calories from fat or from sucrose intake, to plasma cholesterol levels, or to physical fitness (except for a weak association in the latter in white women). The results describe relations between hostility and health behaviors that may be detrimental to health. The findings provide a possible explanation for the association between hostility and coronary heart disease mortality.

Young adult blacks and whites aged 18-30 years of both low and high educational levels were recruited through random digit dialing to participate in the Chicago, Illinois, portion of a longitudinal study, Coronary Artery Risk Development in Young Adults (CARDIA). Overall, 31% of randomly selected persons eligible to participate had unlisted telephone numbers--about 50% of black men and women and 11% and 17% of white men and women, respectively. There was no difference in proportions of numbers unlisted by educational level, except for white men, who were more likely to have unlisted numbers at a low educational level than at a high educational level. There was no consistent pattern of differences in rates of participation across race, sex, or education subgroups for unlisted and listed numbers, and there were no significant differences for selected health measures, except smoking. The findings suggest that in Chicago, there is a potential bias in estimates of sociodemographic characteristics from the exclusion of unlisted numbers, but it is likely to be insignificant if recruitment is stratified according to race, sex, and education. Within strata, there was little bias with respect to the attributes measured. Ideally, to guard against possible bias, random digit dialing is recommended as the preferred way to select a representative population-based sample.

Probably the single largest advantage of the inertial route to fusion energy (IFE) is the perception that its power plant embodiments could achieve acceptable capacity factors. This is a result of its relative simplicity, the decoupling of the driver and reactor chamber, and the potential to employ thick liquid walls. We examine these issues in terms of the complexity, reliability, maintainability and, therefore, availability of both magnetic and inertial fusion power plants and compare these factors with corresponding scheduled and unscheduled outage data from present day fission experience. We stress that, given the simple nature of a fission core, the vast majority of unplanned outages in fission plants are due to failures outside the reactor vessel itself. Given we must be prepared for similar outages in the analogous plant external to a fusion power core, this puts severe demands on the reliability required of the fusion core itself. We indicate that such requirements can probably be met for IFE plants. We recommend that this advantage be promoted by performing a quantitative reliability and availability study for a representative IFE power plant and suggest that databases are probably adequate for this task.

5-HT4 receptors in isolated distal colon myenteric plexus of guinea-pig, mediating contraction of longitudinal smooth muscle, have been further characterized by selective agonists and antagonists. The indole agonists, 5-HT and 5-methoxytryptamine (5-MeOT), were full agonists (relative to 5-HT) with potency values (pEC50) of 8.0 ± 0.1 (n = 50) and 7.8 ± 0.1 (n = 12), respectively. 5-HT4 receptor agonists of other structural classes, including benzimidazolones (BIMU 1 and BIMU 8), and benzamides ((S)-zacopride, (R)-zacopride, renzapride, SC 49518) were partial agonists with intrinsic activities less than that of 5-HT. In general, the potencies for these compounds at 5-HT4 receptors in guinea-pig colon were similar to the potencies seen in the rat isolated oesophagus, where 5-HT4 receptors mediate relaxation.

Agonist-induced desensitization has been utilized to discriminate and independently “isolate” the neuronal excitatory receptors to 5-hydroxytryptamine (5-HT) in the guinea pig ileum (5-HT3 and putative 5-HT4 receptors). Electrically stimulated longitudinal muscle myenteric plexus preparations, and non-stimulated segments of whole ileum were used. Exposure to 5-methoxytryptamine (10 µmol/l) inhibited completely responses to 5-HT at the putative 5-HT4 receptor without affecting 5-HT3-mediated responses. Conversely, exposure to 2-methyl-5-HT (10 µmol/l) inhibited completely responses to 5-HT at the 5-HT3 receptor without affecting putative 5-HT4-mediated responses. The inhibition with 5-methoxytryptamine and 2-methyl-5-HT, either alone or in combination, appeared selective as responses to KCI, DMPP, carbachol, histamine, and substance P were unaffected or only very slightly modified. Furthermore, the pA2 values for ICS 205–930 at the putative 5-HT4 (pA2 = 6.2 to 6.5) and 5-HT3 (pA2 = 7.6 to 8.1) receptors (estimated in the presence of 2-methyl-5HT and 5-methoxytryptamine, respectively) were consistent with those estimated in the absence of desensitization.

A specific binding site for 1-[3H]stearoyl-lysophosphatidic acid (stearoyl-LPA) was identified and characterized in membranes prepared from rat brain and Swiss 3T3 fibroblasts. Specific binding of [3H]LPA to these sites was protein dependent, was saturable, reached equilibrium in 15 min, and was displacable by the addition of excess unlabeled LPA. Scatchard analysis of saturation binding experiments indicated that these sites had affinities of 2.0 +/- 0.5 nM and 5.4 +/- 2.6 nM and densities of 19 +/- 3 fmol/micrograms of protein and 38 +/- 6 fmol/micrograms of protein in rat brain and 3T3 cell membranes, respectively. Various LPAs, with different acyl groups in the sn-1-position, competed with [3H]LPA for these binding sites, with a rank order of potency of 1-oleoyl-LPA > 1-stearoyl-LPA = 1-palmitoyl-LPA > 1-myristoyl-LPA. Phosphatidic acid also bound to these sites, but with lower affinity than any LPA tested. Neither lysophosphatidylcholine, lysophosphatidylethanolamine, nor any free fatty acid competed with [3H]LPA for these binding sites. Binding of [3H]LPA to these sites was regulated by nonhydrolyzable guanine nucleotides in both rat brain and 3T3 cell membranes. Furthermore, in 3T3 cells, these sites were regulated by cell density. It was subsequently determined that LPA induced a transient increase in intracellular Ca2+ levels in 3T3 cells. The concentrations required for this response, as well as the rank order of potency of the various LPAs and phosphatidic acid, correlated with the affinity of these compounds for the [3H]LPA binding site. These results suggest that the specific, high affinity, binding sites for [3H]LPA are G protein-coupled receptors.