Liquid flyback booster pre-phase: A study assessment

The concept of a flyback booster has been around since early in the shuttle program. The original two-stage shuttle concepts used a manned flyback booster. These boosters were eliminated from the program for funding and size reasons. The current shuttle uses two Redesigned Solid Rocket Motors (RSRM's), which are recovered and refurbished after each flight; this is one of the major cost factors of the program. Replacement options have been studied over the past ten years. The conclusion reached by the most recent study is that the liquid flyback booster (LFBB) is the only competitive option from a life-cycle cost perspective. The purpose of this study was to assess the feasibility and practicality of LFBB's. The study provides an expansion of the recommendations made during the aforementioned study. The primary benefits are the potential for enhanced reusability and a reduction of recurring costs. The potential savings in vehicle turnaround could offset the up-front costs. Development of LFBB's requires a commitment to the shuttle program for 20 to 30 years. LFBB's also offer enhanced safety and abort capabilities. Currently, any failure of an RSRM can be considered catastrophic, since there are no intact abort capabilities during the burn of the RSRM's. The performance goal of the LFBB's was to lift a fully loaded orbiter under optimal conditions, so as not to be the limiting factor of the performance capability of the shuttle. In addition, a final benefit is the availability of growth paths for applications other than shuttle

Racial Disparities Across Provider Specialties in Opioid Prescriptions Dispensed to Medicaid Beneficiaries with Chronic Noncancer Pain

Chronic pain affects both psychological and physical functioning, and is responsible for more than $60 billion in lost productivity annually in the United States. Although previous studies have demonstrated racial disparities in opioid treatment, there is little evidence regarding disparities in treatment of chronic non-cancer pain (CNCP) and the role of physician specialty

Superconductors with Magnetic Impurities: Instantons and Sub-gap States

When subject to a weak magnetic impurity potential, the order parameter and quasi-particle energy gap of a bulk singlet superconductor are suppressed. According to the conventional mean-field theory of Abrikosov and Gor'kov, the integrity of the energy gap is maintained up to a critical concentration of magnetic impurities. In this paper, a field theoretic approach is developed to critically analyze the validity of the mean field theory. Using the supersymmetry technique we find a spatially homogeneous saddle-point that reproduces the Abrikosov-Gor'kov theory, and identify instanton contributions to the density of states that render the quasi-particle energy gap soft at any non-zero magnetic impurity concentration. The sub-gap states are associated with supersymmetry broken field configurations of the action. An analysis of fluctuations around these configurations shows how the underlying supersymmetry of the action is restored by zero modes. An estimate of the density of states is given for all dimensionalities. To illustrate the universality of the present scheme we apply the same method to study `gap fluctuations' in a normal quantum dot coupled to a superconducting terminal. Using the same instanton approach, we recover the universal result recently proposed by Vavilov et al. Finally, we emphasize the universality of the present scheme for the description of gap fluctuations in d-dimensional superconducting/normal structures.Comment: 18 pages, 9 eps figure

Liquid Flyback Booster Pre-Phase A Study Assessment

Mw concept of a flyback booster has been around since early in the Shuttle program. The original two-stage Shuttle concepts used a manned flyback booster. These boosters were eliminated from the program for funding and size reasons. The current Shuttle uses two Redesigned Solid Rocket Motors (RSRMs), which are recovered and refurbished after each flight; this is one of the major cost factors of the program. Replacement options have been studied over the past ten years. The conclusion reached by the most recent study is that the liquid flyback booster (LFBB) is the only competitive option from a life-cycle cost perspective. The purpose of this study was to assess the feasibility and practicality of LFBBs. The study provides an expansion of the recommendations made during the during the aforementioned study. The primary benefits are the potential for enhanced reusability and a reuction of recurring costs. The potential savings in vehicle turnaround could offset the up-front costs. Development of LFBBs requires a commitment to the Shuttle program for 20 to 30 years. LFBBs also offer enhanced safety and abort capabilities. Currently, any failure of an RSRM can be considered catastrophic since them we no intact abort capabilities during the burn of the RSRMS. The performance goal of the LFBBs was to lift a fully loaded Orbiter under optimal conditions, so as not to be the limiting factor of the performance capability of the Shuttle. In addition, a final benefit is the availability of growth paths for applications other than the Shuttle

Highly efficient separation of actinides from lanthanides by a phenanthroline-derived bis-triazine ligand

The synthesis, lanthanide complexation, and solvent ex- traction of actinide(III) and lanthanide(III) radiotracers from nitric acid solutions by a phenanthroline-derived quadridentate bis-triazine ligand are described. The ligand separates Am(III) and Cm(III) from the lanthanides with remarkably high efficiency, high selectivity, and fast extraction kinetics compared to its 2,2'-bipyridine counterpart. Structures of the 1:2 bis-complexes of the ligand with Eu(III) and Yb(III) were elucidated by X-ray crystallography and force field calculations, respec-tively. The Eu(III) bis-complex is the first 1:2 bis-complex of a quadridentate bis-triazine ligand to be characterized by crystallography. The faster rates of extraction were verified by kinetics measurements using the rotating membrane cell technique in several diluents. The improved kinetics of metal ion extraction are related to the higher surface activity of the ligand at the phase interface. The improvement in the ligand's properties on replacing the bipyridine unit with a phenanthroline unit far exceeds what was anticipated based on ligand design alone

A “Coiled-Coil” Motif Is Important for Oligomerization and DNA Binding Properties of Human Cytomegalovirus Protein UL77

Human cytomegalovirus (HCMV) UL77 gene encodes the essential protein UL77, its function is characterized in the present study. Immunoprecipitation identified monomeric and oligomeric pUL77 in HCMV infected cells. Immunostaining of purified virions and subviral fractions showed that pUL77 is a structural protein associated with capsids. In silico analysis revealed the presence of a coiled-coil motif (CCM) at the N-terminus of pUL77. Chemical cross-linking of either wild-type pUL77 or CCM deletion mutant (pUL77ΔCCM) implicated that CCM is critical for oligomerization of pUL77. Furthermore, co-immunoprecipitations of infected and transfected cells demonstrated that pUL77 interacts with the capsid-associated DNA packaging motor components, pUL56 and pUL104, as well as the major capsid protein. The ability of pUL77 to bind dsDNA was shown by an in vitro assay. Binding to certain DNA was further confirmed by an assay using biotinylated 36-, 250-, 500-, 1000-meric dsDNA and 966-meric HCMV-specific dsDNA designed for this study. The binding efficiency (BE) was determined by image processing program defining values above 1.0 as positive. While the BE of the pUL56 binding to the 36-mer bio-pac1 containing a packaging signal was 10.0±0.63, the one for pUL77 was only 0.2±0.03. In contrast to this observation the BE of pUL77 binding to bio-500 bp or bio-1000 bp was 2.2±0.41 and 4.9±0.71, respectively. By using pUL77ΔCCM it was demonstrated that this protein could not bind to dsDNA. These data indicated that pUL77 (i) could form homodimers, (ii) CCM of pUL77 is crucial for oligomerization and (iii) could bind to dsDNA in a sequence independent manner

A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques

The recurrence of new human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the need for effective therapeutic countermeasures. Nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. However, MERS-CoV-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. Considering this limitation, we wanted to ascertain the effectiveness of using a MERS-CoV infectious clone (icMERS-0) previously shown to replicate to higher titers than the wild-type EMC 2012 strain. We observed respiratory disease resulting from exposure to the icMERS-0 strain as measured by CT in rhesus monkeys with concomitant detection of virus antigen by immunohistochemistry. Overall, respiratory disease was mild and transient, resolving by day 30 post-infection. Although pulmonary disease was mild, these results demonstrate for the first time the utility of CT imaging to measure disease elicited by a MERS-CoV infectious clone system in nonhuman primate models

O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis

The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. However, how these crucial protein–protein interactions can be dynamically regulated during plant development remains unclear. Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors—PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)—that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development

Impairment of Gradual Muscle Adjustment during Wrist Circumduction in Parkinson's Disease

Purposeful movements are attained by gradually adjusted activity of opposite muscles, or synergists. This requires a motor system that adequately modulates initiation and inhibition of movement and selectively activates the appropriate muscles. In patients with Parkinson's disease (PD) initiation and inhibition of movements are impaired which may manifest itself in e.g. difficulty to start and stop walking. At single-joint level, impaired movement initiation is further accompanied by insufficient inhibition of antagonist muscle activity. As the motor symptoms in PD primarily result from cerebral dysfunction, quantitative investigation of gradually adjusted muscle activity during execution of purposeful movement is a first step to gain more insight in the link between impaired modulation of initiation and inhibition at the levels of (i) cerebrally coded task performance and (ii) final execution by the musculoskeletal system. To that end, the present study investigated changes in gradual adjustment of muscle synergists using a manipulandum that enabled standardized smooth movement by continuous wrist circumduction. Differences between PD patients (N = 15, off-medication) and healthy subjects (N = 16) concerning the relation between muscle activity and movement performance in these groups were assessed using kinematic and electromyographic (EMG) recordings. The variability in the extent to which a particular muscle was active during wrist circumduction – defined as muscle activity differentiation - was quantified by EMG. We demonstrated that more differentiated muscle activity indeed correlated positively with improved movement performance, i.e. higher movement speed and increased smoothness of movement. Additionally, patients employed a less differentiated muscle activity pattern than healthy subjects. These specific changes during wrist circumduction imply that patients have a decreased ability to gradually adjust muscles causing a decline in movement performance. We propose that less differentiated muscle use in PD patients reflects impaired control of modulated initiation and inhibition due to decreased ability to selectively and jointly activate muscles