The nebular circumstellar environments of cool evolved stars are known to harbour a rich morphological complexity of gaseous structures on different length scales. A large part of these density ...structures are thought to be brought about by the interaction of the stellar wind with a close companion. The S-type asymptotic giant branch (AGB) star
π
1
Gruis, which has a known companion at ∼440 au and is thought to harbour a second, closer-by (< 10 au) companion, was observed with the Atacama Large Millimeter/submillimeter Array as part of the A
TOMIUM
Large programme. In this work, the brightest CO, SiO, and HCN molecular line transitions are analysed. The continuum map shows two maxima, separated by 0.04″ (6 au). The CO data unambiguously reveal that
π
1
Gru’s circumstellar environment harbours an inclined, radially outflowing, equatorial density enhancement. It contains a spiral structure at an angle of ∼38 ± 3° with the line-of-sight. The HCN emission in the inner wind reveals a clockwise spiral, with a dynamical crossing time of the spiral arms consistent with a companion at a distance of 0.04″ from the AGB star, which is in agreement with the position of the secondary continuum peak. The inner wind dynamics imply a large acceleration region, consistent with a beta-law power of ∼6. The CO emission suggests that the spiral is approximately Archimedean within 5″, beyond which this trend breaks down as the succession of the spiral arms becomes less periodic. The SiO emission at scales smaller than 0.5″ exhibits signatures of gas in rotation, which is found to fit the expected behaviour of gas in the wind-companion interaction zone. An investigation of SiO maser emission reveals what could be a stream of gas accelerating from the surface of the AGB star to the companion. Using these dynamics, we have tentatively derived an upper limit on the companion mass to be ∼1.1
M
⊙
.
In a bleomycin-induced lung fibrosis model we used wild-type MMTV mice and a triple transgenic mouse SPC-rtTA+/-Tet°Cre+/-LoxP-VEGF-A+/+ to conditionally induce VEGF-A isoform deletion specifically ...in the alveolar type II (ATII) cells of adult mice. Functional murine VEGF-A165b has been described (33). ...a number of regulatory events at the 3' end of the VEGFA A are required for precise physiologic control of VEGF-A bioavailability (34). ...studies have examined VEGF as a single molecule. Alveolar Epithelial Expression of VEGF-Axxxa Is Essential for Development of Pulmonary Fibrosis To determine the effect of VEGF-A on the development of BLM-induced pulmonary fibrosis (44), we generated a triple transgenic mouse SPC-rtTA+/-Tet°Cre+/-LoxPVEGF-A+/+ (termed STCLL) on a C57Bl/6 background to conditionally induce the deletion of VEGF-A isoforms specifically in the ATII cells of adult mice.
A practical asymmetric synthesis of a highly substituted N-acylpyrrolidine on multi-kilogram scale is described. The key step in the construction of the three stereocenters is a 3+2 cycloaddition of ...methyl acrylate and an imino ester prepared from l-leucine t-butyl ester hydrochloride and 2-thiazolecarboxaldehyde. The cycloaddition features novel asymmetric catalysis via a complex of silver acetate and a cinchona alkaloid, particularly hydroquinine, with complete diastereomeric control and up to 87% enantiomeric control. The alkaloid serves as a ligand as well as a base for the formation of the azomethine ylide or 1,3-dipole. Experiments have shown that the hydroxyl group of hydroquinine is a critical element for the enantioselectivities observed. The cycloaddition methodology is also applicable to methylvinyl ketone, providing access to either α- or β-epimers of 4-acetylpyrrolidine depending on the reaction conditions utilized. The synthesis also highlights an efficient N-acylation, selective O- versus N-methylation, and a unique ester reduction with NaBH4−MeOH catalyzed by NaB(OAc)3H that not only achieves excellent chemoselectivity but also avoids formation of the undesired but thermodynamically favored epimer. The highly functionalized target is synthesized in seven linear steps from l-leucine t-butyl ester hydrochloride with all three isolated intermediates being highly crystalline.
A study was designed to simulate the repair of an indirect resin composite restoration with conventionally cured resin composite. Two-part specimens were prepared to test the diametral tensile ...strength of the repair interface between the base material of an indirectly cured resin composite (Herculite XRV) and repairs carried out with three directly cured materials (Herculite XRV, TPH, and Charisma). The repairs were carried out with and without use of the bonding resin for the repair material. The diametral tensile strengths of all repaired specimens were significantly less than those of bulk unrepaired specimens. There were no significant differences between the diametral tensile strengths of repaired blocks when the repair materials were used without bonding resin. The use of an intermediate layer of bonding resin significantly increased the bond strengths obtained when Herculite XRV and TPH were used for repair. There was no significant difference between the strength values of Herculite XRV and TPH, but Charisma exhibited the lowest strengths of repaired specimens.
Recombination of genes is essential to the evolution of genetic diversity, the segregation of chromosomes during cell division, and certain DNA repair processes. The Holiday junction, a four-arm, ...four-strand branched DNA crossover structure, is formed as a transient intermediate during genetic recombination and repair processes in the cell. The recognition and subsequent resolution of Holliday junctions into parental or recombined products appear to be critically dependent on their three-dimensional structure. Complementary NMR and time-resolved fluorescence resonance energy transfer experiments on immobilized four-arm DNA junctions reported here indicate that the Holliday junction cannot be viewed as a static structure but rather as an equilibrium mixture of two conformational isomers. Furthermore, the distribution between the two possible crossover isomers was found to depend on the sequence in a manner that was not anticipated on the basis of previous low-resolution experiments.
The facilitative glucose transporter, GLUT4 undergoes insulin-dependent movement to the cell surface in adipocytes. The magnitude of the insulin effect is much greater for GLUT4 than other recycling ...proteins such as the CD-MPR. In the present study we have studied the colocalisation of these proteins in adipocytes in an effort to explain this selective insulin-dependent recruitment of GLUT4. Using immunofluorescence microscopy or immuno-EM on 3T3-L1 adipocytes we find that there is considerable colocalisation between these proteins particularly within the area of the TGN. However, the distribution of CD-MPR was not significantly effected by insulin. The insulin-dependent recruitment of GLUT4 was concomitant with a selective decrease in GLUT4 labelling of cytoplasmic vesicles whereas the amount of GLUT4 in the TGN region (approx. 50% of total GLUT4) was relatively unaffected. To explore the possibility that the cytoplasmic GLUT4(+) vesicles represent an intracellular insulin-responsive storage compartment we performed quantitative immuno-EM on whole mounts of intracellular vesicles isolated from basal and insulin-stimulated adipocytes. These studies revealed that: (1) GLUT4 and CD-MPR were concentrated in small (30-200 nm) vesicles at a labelling density of 1-20+ gold particles/vesicle; (2) there was significant overlap between both proteins in that 70% of the total GLUT4 pool colocalised with CD-MPR; (3) a significant amount of GLUT4 (approx. 50% of total) was found in a subpopulation of vesicles that contained as little as 5% of the total CD-MPR pool; (4) the GLUT4(+)/CD-MPR(-) vesicles were highly insulin-responsive, and (5) the total number of GLUT4(+) vesicles, but not CD-MPR(+) vesicles, decreased by approx. 30% in response to insulin treatment. These data are consistent with a model in which GLUT4 is selectively sorted into a vesicular compartment in adipocytes that is recruited to the plasma membrane by insulin stimulation.
Abstract only
TPS2086
Background: Brain metastases occur in ~30% of cancer patients. While treatment options continue to evolve, prognosis remains poor in both morbidity and survival, and quality of ...life (QOL) is increasingly emphasized. Most patients will experience cognitive dysfunction. Deficits in executive and self-regulatory functions, memory, and communication interfere with patients’ functional independence, participation in valued activities, relationships and QOL; they also affect families and caregivers. There are currently no established interventions for oncology and supportive care teams to address cognitive dysfunction and its impact on patient and family QOL. This study targets this gap in knowledge and clinical practice through development and piloting of a novel cognitive support program (CSP) for brain metastasis patients and their primary caregivers. Methods: Building on relevant neuroscience and behavioral research in other cognitively-impaired populations, we designed the CSP as a brief, structured, client-centered program. Using a prospective longitudinal design, 24 cognitively-impaired patients are being recruited from an outpatient multidisciplinary brain metastasis clinic. Each patient, together with their primary caregiver, attends 3 weekly individual sessions to learn strategies for memory, communication and executive functions. At-home practice between sessions applies the strategies in daily activities. Feasibility will be assessed through retention and adherence. Preliminary efficacy will be assessed by reliable change on cognitive, functional and QOL measures completed by patients pre-, post-, and 3 months following the CSP intervention. Caregivers will complete ratings of patient functioning and their own QOL at the same intervals. Analyses of variance will examine CSP intervention effects, with regression analyses to explore moderating effects of participant demographics, baseline levels of cognitive impairment, disease and treatment factors (e.g., volume and location of brain lesions, CNS-directed treatments received). Results of this pilot trial will lay the groundwork for a future randomized trial and further development of cognitive supports for brain metastasis patients and their families.
Methicillin-resistant Staphylococcus aureus (MRSA) pulsed-field type (PFT) USA300 causes skin and soft tissue infections in military recruits and invasive disease in hospitals. Chlorhexidine ...gluconate (CHG) is used to reduce MRSA colonization and infection. The impact of CHG on the molecular epidemiology of MRSA is not known.
To evaluate the impact of 2% CHG-impregnated cloths on the molecular epidemiology of MRSA colonization.
Cluster-randomized, double-blind, controlled trial.
Marine Officer Candidate School, Quantico, Virginia, in 2007.
Military recruits.
Thrice-weekly application of CHG-impregnated or control (Comfort Bath; Sage) cloths over the entire body.
Baseline and serial (every 2 weeks) nasal and/or axillary swab samples were assessed for MRSA colonization. Molecular analysis was performed with pulsed-field gel electrophoresis.
During training, 77 subjects (4.9%) acquired MRSA, 26 (3.3%) in the CHG group and 51 (6.5%) in the control group (P=.004). When analyzed for PFT, 24 subjects (3.1%) in the control group but only 6 subjects (0.8%) in the CHG group (P=.001) had USA300. Of the 167 colonizing isolates recovered from 77 subjects, 99 were recovered from the control group, including USA300 (40.4%), USA800 (38.4%), USA1000 (12.1%), and USA100 (6.1%), and 68 were recovered from the CHG group, including USA800 (51.5%), USA100 (23.5%), and USA300 (13.2%).
CHG decreased the transmission of MRSA--more specifically, USA300--among military recruits. In addition, USA300 and USA800 outcompeted other MRSA PFTs at incident colonization. Future studies should evaluate the broad-based use of CHG to decrease transmission of USA300 in hospital settings.
Platelets are the principal component of the innate haemostatic system that protect from traumatic bleeding. We investigated whether lyophilised human platelets (LHPs) could enhance clot formation ...within platelet-free and whole blood environments using an ex vivo model of deep arterial injury. Lyophilised human platelets were produced from stored human platelets and characterised using conventional, fluorescent and electron microscopic techniques. LHPs were resuspended in platelet-free plasma (PFP) obtained from citrated whole human blood to form final concentrations of 0, 20 and 200 x 10⁹ LHPs/L. LHPs with recalcified PFP or whole blood were perfused through the chamber at low (212 s⁻¹) and high (1,690 s⁻¹) shear rates with porcine aortic tunica media as thrombogenic substrate. LHPs shared morphological characteristics with native human platelets and were incorporated into clot generated from PFP or whole blood. Histomorphometrically measured mean thrombus area increased in a dose-dependent manner following the addition of LHPs to PFP under conditions of high shear 704 μm² ± 186 μm² (mean ± SEM), 1,511 μm2 ± 320 μm² and 2,378 μm² ± 315 μm², for LHPs at 0, 20 and 200 x 10⁹ /l, respectively (p= 0.012). Lyophilised human platelets retain haemostatic properties when reconstituted in both PFP and whole blood, and enhance thrombus formation in a model of deep arterial injury. These data suggest that LHPs have the potential to serve as a therapeutic intervention during haemorrhage under circumstances of trauma, and platelet depletion or dysfunction.
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