Studies of homogeneous dirhodium catalyst system

Hydroformylation studies were conducted to investigate the effects of various H&sub2;/CO ratios on rac-[Rh&sub2;H&sub2;(μ-CO)&sub2;(et,ph-P4)]²+;, a dirhodium tetraphosphine catalyst system. Similar experiments were also conducted with monometallic catalysts based on BISBI, NAPHOS, and Xantphos, some of the best bisphosphine ligands for hydroformylation catalysis. This was due to the lack of information in literature on the effects of variable ratios and pressures on activities and selectivities of catalysts that contain bisphosphine ligands, and these studies were also used as a basis of comparison for the dirhodium system. Results indicate that the dirhodium system is more efficient with higher H&sub2;/CO ratios (2:1, 90 psig total pressure appears to be near optimum) with good turnover frequencies, high regioselectivities, and lower catalyst fragmentation reactions in comparison to standard 1:1 H&sub2;/CO conditions. The dirhodium catalyst appears to be extremely sensitive to CO induced loss of Rh to deactivate the catalyst. The monometallic systems show that higher H&sub2;/CO ratios increase catalytic activity and yield higher aldehyde regioselectivities, but also increase the percentage of olefin isomerization. The monometallic systems also demonstrate Rh-induced phosphine fragmentation reactions and catalyst decomposition due to the lower CO partial pressures. Due to the increased activity and selectivity obtained when using a 2:1 H&sub2;/CO ratio, in situ high pressure IR studies were conducted to determine if there were any structural differences between the dirhodium catalyst generated at a 1:1 H&sub2;/CO ratio and a 2:1 H&sub2;/CO ratio. Also due to the increased activity and selectivity in 30% water/acetone (by volume) in comparison to acetone, solvent effect studies were conducted to compare structural differences in acetone and 30% water/acetone. Preliminary IR studies suggest that there are not any structural differences in the 2:1 H&sub2;/CO ratio and 30% water/acetone studies in comparison to standard hydroformylation conditions

Fish introductions and light modulate food web fluxes in tropical streams: a whole-ecosystem experimental approach

Decades of ecological study have demonstrated the importance of top-down and bottom-up controls on food webs, yet few studies within this context have quantified the magnitude of energy and material fluxes at the whole-ecosystem scale. We examined top-down and bottom-up effects on food web fluxes using a field experiment that manipulated the presence of a consumer, the Trinidadian guppy Poecilia reticulata, and the production of basal resources by thinning the riparian forest canopy to increase incident light. To gauge the effects of these reach-scale manipulations on food web fluxes, we used a nitrogen (N-15) stable isotope tracer to compare basal resource treatments (thinned canopy vs. control) and consumer treatments (guppy introduction vs. control). The thinned canopy stream had higher primary production than the natural canopy control, leading to increased N fluxes to invertebrates that feed on benthic biofilms (grazers), fine benthic organic matter (collector-gatherers), and organic particles suspended in the water column (filter feeders). Stream reaches with guppies also had higher primary productivity and higher N fluxes to grazers and filter feeders. In contrast, N fluxes to collector-gatherers were reduced in guppy introduction reaches relative to upstream controls. N fluxes to leaf-shredding invertebrates, predatory invertebrates, and the other fish species present (Hart\u27s killifish, Anablepsoides hartii) did not differ across light or guppy treatments, suggesting that effects on detritus-based linkages and upper trophic levels were not as strong. Effect sizes of guppy and canopy treatments on N flux rates were similar for most taxa, though guppy effects were the strongest for filter feeding invertebrates while canopy effects were the strongest for collector-gatherer invertebrates. Combined, these results extend previous knowledge about top-down and bottom-up controls on ecosystems by providing experimental, reach-scale evidence that both pathways can act simultaneously and have equally strong influence on nutrient fluxes from inorganic pools through primary consumers

Cortical microstructure in young onset Alzheimer's disease using neurite orientation dispersion and density imaging.

Alzheimer's disease (AD) is associated with extensive alterations in grey matter microstructure, but our ability to quantify this in vivo is limited. Neurite orientation dispersion and density imaging (NODDI) is a multi-shell diffusion MRI technique that estimates neuritic microstructure in the form of orientation dispersion and neurite density indices (ODI/NDI). Mean values for cortical thickness, ODI, and NDI were extracted from predefined regions of interest in the cortical grey matter of 38 patients with young onset AD and 22 healthy controls. Five cortical regions associated with early atrophy in AD (entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, fusiform gyrus, and precuneus) and one region relatively spared from atrophy in AD (precentral gyrus) were investigated. ODI, NDI, and cortical thickness values were compared between controls and patients for each region, and their associations with MMSE score were assessed. NDI values of all regions were significantly lower in patients. Cortical thickness measurements were significantly lower in patients in regions associated with early atrophy in AD, but not in the precentral gyrus. Decreased ODI was evident in patients in the inferior and middle temporal gyri, fusiform gyrus, and precuneus. The majority of AD-related decreases in cortical ODI and NDI persisted following adjustment for cortical thickness, as well as each other. There was evidence in the patient group that cortical NDI was associated with MMSE performance. These data suggest distinct differences in cortical NDI and ODI occur in AD and these metrics provide pathologically relevant information beyond that of cortical thinning

Lack of Serologic Evidence of Neospora caninum in Humans, England

Retrospective testing of 3,232 serum samples from the general population and 518 serum samples from a high-risk group showed no evidence of human exposure to Neospora caninum in England. Results were obtained by using immunofluorescence antibody testing and ELISA to analyze frequency distribution

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

SOCS1 Is a Critical Inhibitor of Interferon γ Signaling and Prevents the Potentially Fatal Neonatal Actions of this Cytokine

AbstractMice lacking suppressor of cytokine signaling-1 (SOCS1) develop a complex fatal neonatal disease. In this study, SOCS1−/− mice were shown to exhibit excessive responses typical of those induced by interferon γ (IFNγ), were hyperresponsive to viral infection, and yielded macrophages with an enhanced IFNγ-dependent capacity to kill L. major parasites. The complex disease in SOCS1−/− mice was prevented by administration of anti-IFNγ antibodies and did not occur in SOCS1−/− mice also lacking the IFNγ gene. Although IFNγ is essential for resistance to a variety of infections, the potential toxic action of IFNγ, particularly in neonatal mice, appears to require regulation. Our data indicate that SOCS1 is a key modulator of IFNγ action, allowing the protective effects of this cytokine to occur without the risk of associated pathological responses

Clades of huge phages from across Earth's ecosystems.

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems

Loss and dispersion of superficial white matter in Alzheimer's disease: a diffusion MRI study.

Pathological cerebral white matter changes in Alzheimer's disease have been shown using diffusion tensor imaging. Superficial white matter changes are relatively understudied despite their importance in cortico-cortical connections. Measuring superficial white matter degeneration using diffusion tensor imaging is challenging due to its complex organizational structure and proximity to the cortex. To overcome this, we investigated diffusion MRI changes in young-onset Alzheimer's disease using standard diffusion tensor imaging and Neurite Orientation Dispersion and Density Imaging to distinguish between disease-related changes that are degenerative (e.g. loss of myelinated fibres) and organizational (e.g. increased fibre dispersion). Twenty-nine young-onset Alzheimer's disease patients and 22 healthy controls had both single-shell and multi-shell diffusion MRI. We calculated fractional anisotropy, mean diffusivity, neurite density index, orientation dispersion index and tissue fraction (1-free water fraction). Diffusion metrics were sampled in 15 a priori regions of interest at four points along the cortical profile: cortical grey matter, grey/white boundary, superficial white matter (1 mm below grey/white boundary) and superficial/deeper white matter (2 mm below grey/white boundary). To estimate cross-sectional group differences, we used average marginal effects from linear mixed effect models of participants' diffusion metrics along the cortical profile. The superficial white matter of young-onset Alzheimer's disease individuals had lower neurite density index compared to controls in five regions (superior and inferior parietal, precuneus, entorhinal and parahippocampus) (all P < 0.05), and higher orientation dispersion index in three regions (fusiform, entorhinal and parahippocampus) (all P < 0.05). Young-onset Alzheimer's disease individuals had lower fractional anisotropy in the entorhinal and parahippocampus regions (both P < 0.05) and higher fractional anisotropy within the postcentral region (P < 0.05). Mean diffusivity was higher in the young-onset Alzheimer's disease group in the parahippocampal region (P < 0.05) and lower in the postcentral, precentral and superior temporal regions (all P < 0.05). In the overlying grey matter, disease-related changes were largely consistent with superficial white matter findings when using neurite density index and fractional anisotropy, but appeared at odds with orientation dispersion and mean diffusivity. Tissue fraction was significantly lower across all grey matter regions in young-onset Alzheimer's disease individuals (all P < 0.001) but group differences reduced in magnitude and coverage when moving towards the superficial white matter. These results show that microstructural changes occur within superficial white matter and along the cortical profile in individuals with young-onset Alzheimer's disease. Lower neurite density and higher orientation dispersion suggests underlying fibres undergo neurodegeneration and organizational changes, two effects previously indiscernible using standard diffusion tensor metrics in superficial white matter

Tracking Parkinson's : Study Design and Baseline Patient Data

Peer reviewedPublisher PD

Training of Instrumentalists and Development of New Technologies on SOFIA

This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal Survey (Astro2010)1 Committee on the State of the Profession to emphasize the potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to contribute to the training of instrumentalists and observers, and to related technology developments. This potential goes beyond the primary mission of SOFIA, which is to carry out unique, high priority astronomical research. SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable astronomical observations anywhere, any time, and at most wavelengths between 0.3 microns and 1.6 mm not accessible from ground-based observatories. These attributes, accruing from the mobility and flight altitude of SOFIA, guarantee a wealth of scientific return. Its instrument teams (nine in the first generation) and guest investigators will do suborbital astronomy in a shirt-sleeve environment. The project will invest $10M per year in science instrument development over a lifetime of 20 years. This, frequent flight opportunities, and operation that enables rapid changes of science instruments and hands-on in-flight access to the instruments, assure a unique and extensive potential - both for training young instrumentalists and for encouraging and deploying nascent technologies. Novel instruments covering optical, infrared, and submillimeter bands can be developed for and tested on SOFIA by their developers (including apprentices) for their own observations and for those of guest observers, to validate technologies and maximize observational effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on State of the Professio