Successful completion of a cyclic ground test of a mercury ion auxiliary propulsion system

An engineering model Ion Auxiliary Propulsion System (IAPS) 8-cm thruster (S/N 905) has completed a life test at NASA Lewis Research Center. The mercury ion thruster successfully completed and exceeded the test goals of 2557 on/off cycles and 7057 hr of operation at full thrust. The final 1200 cycles and 3600 hr of the life test were conducted using an engineering model of the IAPS power electronics unit (PEU) and breadboard digital controller and interface unit (DCIU). This portion of the test is described in this paper with a charted history of thruster operating parameters and off-normal events. Performance and operating characteristics were constant throughout the test with only minor variations. The engineering model power electronics unit operated without malfunction; the flight software in the digital controller and interface unit was exercised and verified. Post-test inspection of the thruster revealed facility enhanced accelerator grid erosion but overall the thruster was in good condition. It was concluded that the thruster performance was not drastically degraded by time or cycles. Additional cyclic testing is currently under consideration

Programmed heterogeneity: Epigenetic mechanisms in bacteria

Contrary to the traditional view that bacterial populations are clonal, single-cell analysis reveals that phenotypic heterogeneity is common in bacteria. Formation of distinct bacterial lineages appears to be frequent during adaptation to harsh environments, including the colonization of animals by bacterial pathogens. Formation of bacterial subpopulations is often controlled by epigenetic mechanisms that generate inheritable phenotypic diversity without altering the DNA sequence. Such mechanisms are diverse, ranging from relatively simple feedback loops to complex self-perpetuating DNA methylation patterns

Failure of Intravenous Morphine to Serve as an Effective Instrumental Reinforcer in Dopamine D2 Receptor Knock-Out Mice

The rewarding effects of opiates are thought to be mediated through dopaminergic mechanisms in the ventral tegmental area, dopamine-independent mechanisms in the nucleus accumbens, or both. The purpose of the present study was to explore the contribution of dopamine to opiate-reinforced behavior using D2 receptor knock-out mice. Wild-type, heterozygous, and D2 knock-out mice were first trained to lever press for water reinforcement and then implanted with intravenous catheters. The ability of intravenously delivered morphine to maintain lever pressing in these mice was studied under two schedules of reinforcement: a fixed ratio 4 (FR4) schedule (saline, 0.1, 0.3, or 1.0 mg/kg, per injection) and a progressive ratio (PR) schedule (1.0 mg/kg, per injection). In the wild-type and heterozygous mice, FR4 behavior maintained by morphine injections was significantly greater than behavior maintained by vehicle injections. Response rate was inversely related to injection dose and increased significantly in the wild-type and heterozygous mice when the animals were placed on the PR schedule. In contrast, the knock-out mice did not respond more for morphine than for saline and did not respond more when increased ratios were required by the PR schedule. Thus, morphine served as a positive reinforcer in the wild-type and heterozygous mice but failed to do so in the knock-out mice. Under this range of doses and response requirements, the rewarding effects of morphine appear to depend critically on an intact D2 receptor systemFil: Elmer, Greg I.. University of Maryland; Estados UnidosFil: Pieper, Jeanne O.. National Institutes of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Low, Malcolm J.. Oregon Health and Sciences University; Estados UnidosFil: Grandy, David K.. Oregon Health and Sciences University; Estados UnidosFil: Wise, Roy A.. National Institutes of Health; Estados Unido

Emotional orienting during interoceptive threat in orthostatic intolerance: dysautonomic contributions to psychological symptomatology in the postural tachycardia syndrome and vasovagal syncope

Cognitive and emotional processes are influenced by interoception (homeostatic somatic feedback), particularly when physiological arousal is unexpected and discrepancies between predicted and experienced interoceptive signals may engender anxiety. Due to the vulnerability for comorbid psychological symptoms in forms of orthostatic intolerance (OI), this study investigated psychophysiological contributions to emotional symptomatology in 20 healthy control participants (13 females, mean age 36 ± 8 years), 20 postural tachycardia syndrome (PoTS) patients (18 females, mean age 38 ± 13 years) and 20 vasovagal syncope (VVS) patients (15 females, mean age 39 ± 12 years). We investigated indices of emotional orienting responses (OR) to randomly presented neutral, pleasant and unpleasant images in the supine position and during the induced interoceptive threat of symptom provocation of head-up tilt (HUT). PoTS and VVS patients produced greater indices of emotional responsivity to unpleasant images and, to a lesser degree, pleasant images, during interoceptive threat. Our findings are consistent with biased deployment of response-focused emotion regulation (ER) while patients are symptomatic, providing a mechanistic underpinning of how pathological autonomic overexcitation predisposes to anxiogenic traits in PoTS and VVS patients. This hypothesis may improve our understanding of why orthostasis exacerbates cognitive symptoms despite apparently normal cerebral autoregulation, and offer novel therapeutic targets for behavioural interventions aimed at reducing comorbid cognitive-affective symptoms in PoTS and VVS

Online Adaptive Radiation Therapy: Implementation of a New Process of Care.

Onboard magnetic resonance imaging (MRI) guided radiotherapy is now clinically available in nine centers in the world. This technology has facilitated the clinical implementation of online adaptive radiotherapy (OART), or the ability to alter the daily treatment plan based on tumor and anatomical changes in real-time while the patient is on the treatment table. However, due to the time sensitive nature of OART, implementation in a large and busy clinic has many potential obstacles as well as patient-related safety considerations. In this work, we have described the implementation of this new process of care in the Department of Radiation Oncology at the University of California, Los Angeles (UCLA). We describe the rationale, the initial challenges such as treatment time considerations, technical issues during the process of re-contouring, re-optimization, quality assurance, as well as our current solutions to overcome these challenges. In addition, we describe the implementation of a coverage system with a physician of the day as well as online planners (physicists or dosimetrists) to oversee each OART treatment with patient-specific 'hand-off' directives from the patient's treating physician. The purpose of this effort is to streamline the process without compromising treatment quality and patient safety. As more MRI-guided radiotherapy programs come online, we hope that our experience can facilitate successful adoption of OART in a way that maximally benefits the patient

Macroalgal browsing on a heavily degraded, urbanized equatorial reef system

The removal of macroalgal biomass is critical to the health of coral reef ecosystems. Previous studies on relatively intact reefs with diverse and abundant fish communities have quantified rapid removal of macroalgae by herbivorous fishes, yet how these findings rel ate to degraded reef systems where fish diversity and abundance are markedly lower and algal biomass substantially higher, is unclear. We surveyed roving herbivorous fish communities and quantified their capacity to remove the dominant macroalga Sargassum ilicifolium on seven reefs in Singapore; a heavily degraded urbanized reef system. The diversity and abundance of herbivorous fishes was extremely low, with eight species and a mean abundance ~1.1 individuals 60 m -2 recorded across reefs. Consumption of S. ilicifolium varied with distance from Singapore's main port with consumption being 3- to 17-fold higher on reefs furthest from the port (Pulau Satumu: 4.18 g h -1 ; Kusu Island: 2.38 g h -1 ) than reefs closer to the port (0.35-0.78 g h -1 ). Video observations revealed a single species, Siganus virgatus, was almost solely responsible for removing S. ilicifolium biomass, accounting for 83% of the mass-standardized bites. Despite low herbivore diversity and intense urbanization, macroalgal removal by fishes on some Singaporean reefs was directly comparable to rates reported for other inshore Indo-Pacific reefs

Thermoregulation of \u3ci\u3eEscherichia coil pap\u3c/i\u3e Transcription: H-NS is a Temperature-Dependent DNA Methylation Blocking Factor

The expression of Pap pili that facilitate the attach- ment of Escherichia coli to uroepithelial cells is shut off outside the host at temperatures below 268C. Ribo- nuclease protection analysis showed that this thermo- regulatory response was rapid as evidenced by the absence of papBA transcripts, coding for Pap pilin, after only one generation of growth at 238C. The his- tone-like nucleoid structuring protein H-NS and DNA sequences within papB were required for thermoregu- lation, but the PapB and PapI regulatory proteins were not. In vivo analysis of pap DNA methylation patterns indicated that H-NS or a factor regulated by H-NS bound within the pap regulatory region at 238C but not at 378C, as evidenced by H-NS-dependent inhibi- tion of methylation of the pap GATC sites designated GATC-I and GATC-II. These GATC sites lie upstream of the papBAp promoter and have been shown pre- viously to play a role in controlling Pap pili expression by regulating the binding of Lrp, a global regulator that is essential for activating papBAp transcription. Competitive electrophoretic mobility shift analysis showed that H-NS bound specifically to a pap DNA fragment containing the GATC-I and GATC-II sites. Moreover, H-NS blocked methylation of these pap GATC sites in vitro : H-NS blocked pap GATC methyla- tion at 1.4 mM but was unable to do so at higher con- centrations at which non-specific binding occurred. Thus, non-specific binding of H-NS to pap DNA was not sufficient to inhibit methylation of the pap GATC sites. These results suggest that the ability of H-NS to act as a methylation blocking factor is dependent upon the formation of a specific complex of H-NS with pap regulatory DNA. We hypothesize that a func- tion of H-NS such as oligomerization was altered at 238C, which enabled H-NS to repress pap gene expres- sion through the formation of a specific nucleoprotein complex

Functional plasticity of antibacterial EndoU toxins.

Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CTSTECO31 from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His-His-Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate-specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N-terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA-CTSTECO31 and other clade III toxins are specific anticodon nucleases that cleave tRNAGlu between nucleotides C37 and m2 A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter-bacterial toxin delivery systems

Dopamine D 4 Receptor-Deficient Mice Display Cortical Hyperexcitability

The dopamine D(4) receptor (D(4)R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain dopamine (DA) neurons and is associated with cognitive and emotional processes. However, the physiological significance of this dopamine receptor subtype has been difficult to explore because of the slow development of D(4)R agonists and antagonists the selectivity and efficacy of which have been rigorously demonstrated in vivo. We have attempted to overcome this limitation by taking a multidimensional approach to the characterization of mice completely deficient in this receptor subtype. Electrophysiological current and voltage-clamp recordings were performed in cortical pyramidal neurons from wild-type and D(4)R-deficient mice. The frequency of spontaneous synaptic activity and the frequency and duration of paroxysmal discharges induced by epileptogenic agents were increased in mutant mice. Enhanced synaptic activity was also observed in brain slices of wild-type mice incubated in the presence of the selective D(4)R antagonist PNU-101387G. Consistent with greater electrophysiological activity, nerve terminal glutamate density associated with asymmetrical synaptic contacts within layer VI of the motor cortex was reduced in mutant neurons. Taken together, these results suggest that the D(4)R can function as an inhibitory modulator of glutamate activity in the FC.Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Cepeda, Carlos. University of California at Los Angeles; Estados UnidosFil: Hurst, Raymond S.. University of California at Los Angeles; Estados UnidosFil: Flores Hernandez, Jorge. University of California at Los Angeles; Estados UnidosFil: Ariano, Marjorie A.. The Chicago Medical School; Estados UnidosFil: Falzone, Tomas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Kozell, Laura B.. Oregon Health Sciences University; Estados UnidosFil: Meshul, Charles K.. Oregon Health Sciences University; Estados UnidosFil: Bunzow, James R.. Oregon Health Sciences University; Estados UnidosFil: Low, Malcolm J.. Oregon Health Sciences University; Estados UnidosFil: Levine, Michael S.. University of California at Los Angeles; Estados UnidosFil: Grandy, David K.. Oregon Health Sciences University; Estados Unido

Letters To The Editor.

No abstract available